News & Announcements
Congratulations to ICB&DD Project Member, Dr. Galina Botchkina for having her licensed PPT2 Prostate Cancer Stem Cell Line recently launched as a product catalog in Millipore.
ICB&DD congratulates, Project Member, Dr. Galina Botchkina for having her licensed PPT2 Prostate Cancer Stem Cell Line recently launched as a product catalog (# SCC104) in Millipore.
PPT2 is a spontaneously immortalized prostate cancer cell line that expresses cancer stem cell markers including CD133, CD44, EpCAM and CD166. PPT2 cells possess high sphere-forming, clonogenic and tumorigenic capacities and are extremely resistant to anti-cancer drugs. The PPT2 line is negative for tumor suppressor genes p53 and p21 and do not express AR and PSA, and only a small fraction of the PPT2 cells express p63.
The PPT2 prostate adenocarcinoma cell line was established from a stage pT2c pNX pMX prostate cancer patient. Primary tumor cells were obtained by needle biopsy from the resected prostate carcinoma and established in culture on type-I collagen using serum free stem cell media. PPT2 cells were selected based upon their ability to form 3D spheroids over prolonged passages. Cells were serially transplanted in NOD/SCID mice tumor xenografts and propagated as a mixture of floating 3D spheroids and type I collagen adherent cells. PPT2 is a unique, cancer stem cell (CSC) enriched, human prostate cancer cell line useful for CSC-targeted drug development and research focused on cancer cell and CSC biology. For further details of this announcement please see link below
ICB&DD welcomes Dr. Michael Frohman, Distinguished Professor and Chair, Department of Pharmacological Sciences. We are very pleased that Dr. Frohman has joined ICB&DD as Member, as well as Steering Committee Member. Dr. Frohman received his M.D., Ph.D. from University of Pennsylvania School of Medicine and performed Postdoctoral training at University of California at San Francisco. He is also the Director of the Medical Scientist Training Program at Stony Brook SOM. He is a Fellow of the American Association for the Advancement of Science (AAAS) and Association of American Physicians (AAP). His research is currently focused on Lipid Signaling: Roles in mitochondrial biology, spermatogenesis, diabetes, immune function, the CNS, platelet activation, and cancer; - Imaging Pancreatic β-cells using metabolomics and MRI. Dr. Frohman's research program focuses on the exploration of translational roles for the mammalian family of lipid-signaling Phospholipase D genes. PLD superfamily members are involved in many physiological and pathophysiological settings including immune defenses, cancer, neurodegenerative disease, diabetes, cardiovascular disease, and fertility. His research program will be an excellent addition to the Cancer Research Program of ICB&DD, and also to explore neurodegenerative, metabolic and cardiovascular diseases research at ICB&DD.
ICB&DD welcomes Dr. Michael Airola, Assistant Professor of the Department of Biochemistry and Cell Biology as a Project Member. Dr. Airola's research focuses on the structural biology of lipid modifying enzymes. These enzymes that generate and breakdown bioactive lipids have emerged as therapeutic targets for treating the leading causes of diseases such as cancer, cardiovascular disease, and diabetes. Dr. Airola received his Ph.D. in Chemistry and Chemical Biology from Cornell University (2010) where he studied under guidance of Brian Crane. He performed postdoctoral training at the Medical University of South Carolina, Charleston, 2010-2012 and at Stony Brook University School of Medicine under the guidance of Yusuf Hannun, 2012-2016. His postdoctoral work was focused on a family of bioactive lipids called sphingolipids to understand the molecular basis by which sphingolipids affect cellular processes and how sphingolipid metabolizing enzymes are activated and regulated. During his postdoc training, he was able to establish the prerequisite expression/purification system and crystallized neutral ceramidase to determine its first crystal structure. Dr. Airola will be an ideal member of ICB&DD to strengthening its Structural Biology and Cancer Research Programs, as well as exploring metabolic diseases research at ICB&DD.
ICB&DD welcomes Dr. Dongyan Tan, Assistant Professor, Department of Pharmacological Sciences, School of Medicine, as a Project Member. Dr. Tan received her Ph.D. in Physiology and Biophysics in 2009 from Albert Einstein College of Medicine and completed postdoctoral training in 2016 at Harvard Medical School. She joined the faculty of the Department of Pharmacological Sciences of Stony Brook University as Assistant Professor in 2016. Dr. Tan has a broad background in biochemistry, biophysics, and cell biology, with special training in electron microscopy (EM) and structural biology. She has extensive experience in structural studies of macromolecules complexes using different methods in EM, especially for protein complexes that have proven challenging for traditional structural methods. The overarching goal of her research is to understand how different epigenetic regulators control gene expression through modulating the structure dynamics and the functions of chromatin. Dt. Tan’s laboratory specializes in using EM and a wide array of biochemical and biophysical methods to investigate the structure-function relationships of macromolecular machines that play important roles in epigenetic gene regulation during normal development and in diseases. Dr. Tan’s extensive expertise in cryo-EM will lead the establishment of cryo-EM facility at SBU (CMM Bldg.). She will be an ideal member of ICB&DD, strengthening its Structural Biology Research Program.
ICB&DD Tenth Annual Symposium
(from left to right) Drs. Robert Rizzo, Ken Dill, James Wells, Charles Brooks III, Da-Neng Wang, Wendy Cornell, Leemor Joshua-Tor, Clint Potter, Grant Jensen, Huilin Li, Steven Glynn and Iwao Ojima)
On Thursday, October 6, 2016, the ICB&DD hosted its Tenth Annual Symposium entitled, “Frontiers in Structural and Computational Biology” at the Charles B. Wang Center, Stony Brook University. The Symposium featured eight Plenary Lecturers. Lecturer, Dr. Ken A. Dill, represented the Laufer Center for Physical and Quantitative Biology of Stony Brook University. The event was very well attended by a diversified audience composed of faculty, research staff and students on campus, as well as universities and industries in the Greater New York metropolitan area. The Poster Session equally attracted a large participation of students from Stony Brook University, the Laufer Center for Physical and Quantitative Biology, Mt. Sinai School of Medicine, Chembio Diagnostics Systems Inc., among others. There were 65 scientific posters presented at the Poster Session. Dr. Huilin Li, Professor at the Van Andel Research Institute, former Professor of Biochemistry and Cell Biology, Stony Brook University and Chair of the Symposium Organizing Committee, opened the Symposium and introduced Dr. Richard Reeder, Vice President for Research at Stony Brook University, who gave the welcoming remarks for the Symposium. Then Dr. Lee introduced Dr. Iwao Ojima, Distinguished Professor and Director of ICB&DD. Dr. Ojima concisely summarized the history of accomplishments and the current and future goals of ICB&DD.
Dr. Robert Rizzo, Professor, Department of Applied Mathematics and Statistics, introduced the first Plenary Lecturer, Dr. Wendy Cornell, Principal Research Staff Member, Soft Matter Science, IBM T. J. Watson Research Center, who gave a lecture entitled, “Data Mining and Integration for Drug Discovery Pipeline Decision Support”. In her presentation, Dr. Cornell provided an overview of her research which focuses on the drug discovery process involving numerous stage gates where targets, compounds, clinical trials, and other key options are prioritized and Go/NoGo decisions are made. She described the generation and application of a variety of different decision support models and workflows based on protein structural, protein sequence, and pharmacological data as well as structured and unstructured textual sources and the resulting impact.
Dr. Peter Tonge, Professor, Department of Chemistry, introduced the second Plenary Lecturer, Dr. Da-Neng Wang, Professor, Skirball Institute of Biomolecular Medicine, NYU Medical School, who gave a lecture entitled, “Structure and Mechanism of a Bacterial Sodium-Dependent Dicarboxylate Transporter- Implications in Fatty Acid Synthesis and Obesity”. In his presentation, Dr. Wang discussed the factors, such as its direct import across the plasma membrane via the Na+- dependent citrate transporter (NaCT) which influence the concentration of cytosolic citrate, a major precursor for the synthesis of fatty acids, triacylglycerols, cholesterol and low density lipoprotein in liver and adipose cells. He stated that mutations of the homologous transporter gene in flies (INDY) result in reduced fat storage through calorie restriction. His research team has determined the 3.2 Å crystal structure an INDY homolog from Vibrio cholera. In conclusion, he indicated that homology modeling of the human NaCT protein has been used to understand its interaction with various small molecules.
Dr. David Green, Associate Professor, Department of Applied Mathematics and Statistics, introduced the third Plenary Lecturer, Dr. Ken A. Dill, Distinguished Professor and Director of the Laufer Center for Physical and Quantitative Biology, Member of the National Academy of Sciences, who gave a lecture entitled, “Melding Physical Simulations with Fuzzy Information for Computational Folding and Binding”. In his presentation, Dr. Dill discussed the computing of the folded or docked structures of proteins using physics-based molecular simulations. He stated that physical simulations have the advantage of capturing energies in addition to structural information, satisfying the Boltzmann distribution law, and giving dynamic and mechanistic information. He described the MELD method where he and his research team would speed up physical simulations by using fuzzy and uncertain external information and how MELD could help in experimental structure determination and finding native states of small proteins. He concluded by stating that he was optimistic that the MELD accelerator would add value to molecular dynamics modeling.
Dr. Markus Seeliger, Associate Professor, Department of Pharmacological Sciences, introduced the fourth Plenary Lecturer, Dr. James Wells, Chair, Department of Pharmaceutical Chemistry, University of California, San Francisco, who gave a lecture entitled, “Challenging Targets for Drug Discovery: ‘The High Hanging Fruit’”. In his presentation, Dr. Wells described Tethering, a fragment-based discovery approach used to probe the surfaces of proteins that engage in protein-protein interactions or that may be regulated by allosteric interactions. He stated that for these sites, plasticity and conformational adaptability of proteins has begun to reveal new opportunities for drug discovery on targets previously assumed to be undruggable. Although protein-protein interfaces are generally flat and large, small fragment molecules can be found that bind with much greater ligand efficiency to “hot-spots” and in crevices that protein partners do not exploit. In addition, the site-directed nature of Tethering makes it very useful for exploring allosteric sites that may not be found by typical screening approaches. These technologies and the intrinsic adaptability and flexibility of proteins dramatically expand the opportunities for drug discovery at protein-protein interfaces and allosteric sites.
Dr. Huilin Li, Professor at the Van Andel Research Institute and former Professor of Department of Biochemistry and Cell Biology at Stony Brook University, introduced the fifth Plenary Lecturer, Dr. Grant Jensen, Principal Investigator, HHMI and California Institute of Technology, Department of Biology, Broad Center for the Biological Sciences, who gave a presentation entitled, “Structural Biology in vivo Through Electron Cryotomography”. In his presentation, Dr. Jensen stated that in the last ten years, electron cryotomography has made it possible to visualize large macromolecular assemblies inside intact cells in a near-native, "frozen-hydrated" state in 3-D to a few nanometers resolution and that atomic models of individual proteins and smaller complexes obtained by X-ray crystallography, NMR spectroscopy, or other methods can be fit into cryotomograms to reveal how the various pieces work together inside cells. He stressed that a few good pictures are sometimes all that is needed to distinguish between competing models. Dr. Jensen then summarized the key technological advances that have made electron cryotomography possible and then presented several examples of current results from his research group’s recent work in bacterial cell biology, including new images and mechanistic insights into bacterial chemoreceptor arrays, secretion systems, and the Type IV pilus to illustrate these points.
Dr. Liang Gao, Assistant Professor, Department of Chemistry, introduced the sixth Plenary Lecturer, Dr. Clint Potter, Co-Director, Electron Microscopy, New York Structural Biology Center, who gave a lecture entitled, “New Challenges for Molecular Electron Microscopy”. In his presentation, Dr. Potter focused on the dramatic improvements in the progress of Molecular Electron Microscopy (EM), and a set of techniques and approaches used to analyze the structure of macromolecular machines using a transmission electron microscope (TEM). He stated that new detectors and image processing software have enabled the reconstruction of atomic resolution maps for large well-ordered macromolecules and that high levels of automation in image acquisition and processing have enabled the reconstruction of multiple different states of molecular machines from a single sample. Dr. Potter then provided an overview of the new technology being used to understand structures that may be highly heterogeneous and/or dynamic and illustrated how the power of this method can be applied in the understanding of molecular machines.
Dr. Miguel Garcia-Diaz, Associate Professor, Department of Pharmacological Sciences, introduced the seventh Plenary Lecturer, Dr. Leemor Joshua-Tor, Professor and Dean of Watson School of Biological Sciences, HHMI Investigator, Cold Spring Harbor Laboratory and HHMI, who gave a presentation entitled, “Mad About U: Regulating the Let7 Pre-miRNA”. In her presentation, Dr. Tor explored the key mechanistic features of the steps in the regulation of the let-7 family of regulatory miRNA. She stated that Lin28 is the pluripotency factor that inhibits the biogenesis of the let-7 family. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in development and tissue regeneration. It is an oncogene in a subset of human cancers, while let-7 is a tumor suppressor, that silences several human oncogenes. She described the process by which Lin28 triggers the suppression of mature let-7 expression in stem cells and certain cancer cells.
Dr. Carlos Simmerling, Professor, Department of Chemistry, introduced the eighth Plenary Lecturer, Dr. Charles L. Brooks III, Warner-Lambert/Parke-Davis Professor of Chemistry and Biophysics, Department of Chemistry and Biophysics, University of Michigan, who gave a presentation entitled, “High-Throughput, Free Energy Based Ligand Discovery and Optimization Using Multi-Site λ-Dynamics”. In his presentation, Dr. Brooks discussed his research group’s development of an extended Lagrangian approach to free energy simulations called λ-dynamics and a multi-site version, which he termed multi-site λ-dynamics. He stressed that this system of interest “’evolves’ dynamically in the space of chemical substituents of interest and thus significantly enhances the efficiency of the search problem and convergence of the overall free energy calculations”. Dr. Books then described the extended Lagrangian methodology and illustrated it in the context of large- scale ligand screening calculations and then concluded his presentation by discussing generalizations to permit both sequence-based resistant mutations and ligand affinities.
Dr. Robert Rizzo gave the closing remarks, thanking the Plenary Lecturers for their outstanding presentations as well as the Organizing Committee members for their successful planning and execution of the Tenth Annual ICB&DD Symposium.
The best three of the 65 posters presented in the Poster Session were selected for the Poster Awards. The award winning posters this year were presented by Amber Bonds from the research group of Dr. Nicole Sampson for her poster entitled, “Elucidating the Mechanisms of Cholesterol Metabolism in Mycobacterium Tuberculosis”; T. Dwight McGee Jr. from the research group of Dr. Robert Rizzo for his poster entitled, “Exploiting Targetable Events in HIV Entry with Small-Molecule Inhibitors” and Xin Wang from the research group of Dr. Iwao Ojima for her poster entitled, “SB-T-1214 and Biotin Functionalized Gold Nanoparticles”.
The 10th ICB&DD Symposium culminated with a wonderful dinner at the Chapel of the Charles B. Wang Center. Among the attendees were Kenneth Shroyer, Chair of the Department of Pathology and Maria Ryan, Chair of the Department of Oral Biology and Pathology. They expressed their appreciation for the outstanding lectures presented at the symposium as well as acknowledged the significance of the ICB&DD and the collaborative efforts among academia and industry. They also commended Dr. Ojima for his successful leadership for the ICB&DD operation and holding decade-long cutting-edge Symposiums. Dr. Ojima extended special thanks to Ms. Roxanne Brockner, Assistant to the Director for her exceptional and dedicated efforts for the success of ICB&DD and its Symposiums.
The Symposium was co-sponsored by the Office of the Vice-President for Research, Stony Brook School of Medicine, Department of Chemistry, TargaGenix Inc., Chembio Diagnostics Systems Inc., Chem-Master International, Inc. and Hoffmann and Baron LLP.
Congratulations to Drs. Francis Johnson and Maria Ryan, Co-Investigators of a newly funded grant from the National Institute of Dental and Craniofacial Research (NIDCR) to advance treatment of Periodontal Disease.
In a pioneering partnership that could lead to new treatments for periodontal disease, Stony Brook University’s School of Dental Medicine and Traverse Biosciences have received a $1.3 million award from the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health (NIH). The funding is intended to further evaluate the pre-clinical safety and effectiveness of the Traverse’s leading drug candidate, TRB-N0224, for the treatment of periodontal disease. The research will be led by Lorne Golub, DMD, in the Department of Oral Biology and Pathology, and Ying Gu, PhD, DDS, in the Department of General Dentistry at the School of Dental Medicine. They will serve as co-principle investigators of the award, in close collaboration with Traverse Biosciences.
Periodontal disease is one of the most prevalent diseases in the world, includes the major conditions of gingivitis and periodontitis, and is the primary cause of tooth loss in adults. The Centers for Disease Control (CDC) estimates that the prevalence of periodontitis in U.S. adults aged 30 years and older is 47.2% (64.7 million people). Periodontal disease has also been associated with other chronic conditions such as heart disease, diabetes, and various cancers. Periodontal disease also impacts companion animals, including dogs, cats and horses. Canine periodontal disease affects approximately 80% of dogs by the age of three, with the highest incidence in smaller breeds and older animals.
In 2015, Traverse Biosciences signed an exclusive, worldwide license agreement with the Research Foundation for the State University of New York to develop a drug to treat canine periodontal disease. The leading drug candidate that has emerged and will be evaluated under the this NIDCR grant is derived from laboratory discoveries by Dr. Golub and Dr. Francis Johnson, President of Chem-Master International Inc., and Professor of Chemistry and Pharmacological Sciences at Stony brook University. They developed a library of drug candidates that are chemically-modified curcumins, which are designed to treat inflammation. The patents for the novel compounds list Drs. Golub and Johnson as the inventors. Traverse Biosciences will evaluate TRB-N0224 for the treatment of periodontal disease in both humans and animals.
“I am very pleased that Traverse Biosciences has been able to attract the financial resources necessary to advance this highly collaborative research and development program,” said Dr. Golub, SUNY Distinguished Professor and also a Scientific Co-Founder of Traverse Biosciences. “With this critical support from NIDCR, we can accelerate the commercialization of this platform technology for the treatment of periodontal disease, as well as a variety of other chronic inflammatory conditions.”
Joseph Scaduto, MS, MBA, Founder and CEO of Traverse Biosciences, stated, “We are working to successfully commercialize TRB-N0224 as an FDA-approved pharmaceutical intervention for the treatment of chronic inflammatory diseases in both humans and companion animals, including periodontal disease.” He added, “This award from the National Institute of Dental and Craniofacial Research provides an infusion of non-dilutive capital that will allow us to demonstrate the pre-clinical safety and efficacy of this lead drug candidate.”
Dr. Gu, Associate Professor of Dentistry, commented, “I look forward to evaluating the therapeutic efficacy of TRB-N0224 to treat periodontal disease, and I am very pleased to work with Traverse Biosciences on this project. I strongly believe there is a need to develop new and improved therapeutics to manage chronic inflammatory diseases such as periodontitis. With this grant, we, as a team with Dr. Hsi-Ming Lee, a Research Assistant Professor in Oral Biology and Pathology, will be able to advance our research from bench top to chair side, from idea to commercialization.” She added, “It is exciting to work closely with a new venture to develop a promising biomedical technology invented here at Stony Brook University”
Dr. Maria Ryan, a Co-Investigator on the award and Chair of the Department of Oral Biology and Pathology said, “The Department of Oral Biology and Pathology has been a prolific source of innovation throughout its history with numerous products successfully developed and commercialized. I am so proud to see this legacy continue with the invention of TRB-N0224 and our fruitful partnership with Traverse Biosciences.”
The NIDCR award is defined as a Phase II Small Business Technology Transfer (STTR) grant. Some of the STTR funding goes directly to the laboratory of Drs. Golub and Gu, and the work they and colleagues are doing evaluating the compounds in the School of Dental Medicine. The other portion of the funding goes to Traverse Bioscience for drug development and commercialization.
From Stony Brook Happenings. See article
We are pleased to announce the ICB&DD 10th Annual Symposium, “ Frontiers in Structural and Computational Biology”, which will be held at the Charles B. Wang Center on Thursday, October 6 2016 (9:00AM–5PM; Reception 5:00–6:00PM). The ICB&DD Annual Symposium is thematically focused on cutting-edge advances in chemical biology, structural and computational biology, cancer and infectious diseases, and drug discovery. The Symposium invites renowned scholars in the field as well as highly recognized researchers on campus to present their exciting accomplishments and stimulate exchange of innovative ideas among speakers, faculty, staff, and students on campus as well as researchers at the Brookhaven National Laboratory, academia and industries in the greater NY metropolitan area.
The Plenary Lecturers this year are:
Dr. Grant Jensen, Howard Hughes Medical Institute, California Institute of Technology
Dr. Clint Potter, Simons Electron Microscopy Center, New York
Dr. Neng Wang, Skirball Institute, New York University Medical School
Dr. Leemor Joshua-Tor, Howard Hughes Medical Institute and Cold Spring Harbor Laboratory
Dr. Kenneth Dill, Laufer Center, Stony Brook University
Dr. Charles L. Brooks III, University of Michigan,
Dr. James Wells, University of California, San Francisco
Dr. Wendy Cornell, IBM
There will be Poster sessions on recently completed and ongoing projects conducted in the ICB&DD member's laboratories as well as relevant research laboratories in the area.
We are looking forward to another stimulating and productive symposium!
Antifungal Work Lands Dr. Maurizio Del Poeta $6 million from NIH
Like the fictional Steve Austin, Stony Brook University’s Maurizio Del Poeta has become the ““Six Million Dollar Man.”
No, Del Poeta didn’t crash in an experimental spacecraft; and no, he doesn’t have bionic limbs. Instead, work with a potentially deadly fungus in his laboratory helped Del Poeta, a professor in the Department of Molecular Genetics & Microbiology at Stony Brook University, earn two, multiyear $3 million grants from the National Institutes of Health. Del Poeta is attacking a fungus that can be deadly, particularly for people with weakened immune systems. Recently, his approach yielded an unexpected result that may lead to a vaccine. “We were looking for a gene that would metabolize a fungal sphingolipid on the surface of the fungus,” he said. The gene he mutated caused a different function than expected, leading mice with exposure to this strain to become resistant to fungal infection, Del Poeta said. This change may be the key to providing a vaccination against Cryptococcus neoformans, a fungus present in numerous places, including in bird droppings. “We think that this discovery will open the road to a new vaccination strategy against fungi” including candidiasis caused by Candida albicans or aspergillosis, caused byAspergillus funigatus, Del Poeta said. The same gene for sterol glucosidase that Del Poeta and the researchers in his lab mutated is also found in the genome of these other fungal species. “One could potentially make a vaccine containing the three fungal mutants combined and inject them together to protect simultaneously” against all three species, he said. These three infections account for over 1.3 million deaths per year, according to the Centers for Disease Control and Prevention. This vaccine could prove effective for immunocompetent and immunocompromised individuals. A potential vaccine is particularly important for the latter group.
Del Poeta and his colleagues injected the mutated version of the fungus into an animal model that mirrored the conditions of a patient with the human immunodeficiency virus. The vaccine “protected 100 percent” against an infection, Del Poeta said. “Whatever this mutant is doing, the protection is not determined by the presence of CD4 cells.” CD4 cells are a type of white blood cell that fights infection. They are at the center of vaccines that train the immune system to recognize and destroy live versions of infections. Without those cells, vaccination becomes more difficult, but, clearly, not impossible. His results earned him a 1 score, the top mark from reviewers, from the National Institutes of Health, which recently awarded him a $3 million grant to study this mutated fungus. The grant should become active on July 1. John Perfect, the James B. Duke Professor of Medicine and chief of the Division of Infections Disease at Duke University, brought Del Poeta into his laboratory from Italy. He is proud of his protege, describing Del Poeta in an email as a “major investigator in fungal pathogenesis.” An important question Del Poeta can’t answer is how this attenuated strain conveys resistance. Before this promising early work can become a part of preventive treatment, Del Poeta said he and his team will look for a different formulation of this potential vaccine.
“It will be difficult to convince the FDA to administer a live fungus to an immunocompromised patient, even if the fungus will be attenuated,” he explained. “So, we need to make a better vaccine.” His postdoctoral researcher, Antonella Rella, who is the first author on a paper published in Frontiers in Microbiology describing their results, is making and testing new formulations. She has already found promising results using only certain portions of the cell, Del Poeta said.
Del Poeta is also working in drug development. He received a $3 million grant this past December from the NIH for his continued work on drugs to treat fungal infections. Last June, Del Poeta published a study in mBio, the online journal of the American Society for Microbiology, in which he found two compounds, BHBM and its derivative DO, that decreased the level of a lipid fungal cells need to reproduce. Since then, he has found that some derivatives are more potent and less toxic.
He has teamed up with Iwao Ojima, the director of the Institute of Chemical Biology and Drug Discovery at Stony Brook University, and John Mallamo, who was a director in drug discovery at Cephalon. The scientific team is working with Brian McCarthy, an entrepreneur-in-residence, as a part of a new company called MicroRid Technologies. The first milestone in the next three to four years is to raise additional funds for FDA filing and to perform a Phase 1 clinical trial some time between 2018 and 2020.
Del Poeta “exudes optimism” and his “scientific rigor and thoughts are simply first rate,” said Perfect. When he’s not working to stop potentially deadly fungal infections, Del Poeta lives in Mount Sinai with his wife Chiara Luberto, who is studying leukemia at the Cancer Center at Stony Brook, and his sons Matteo, who is 9, and Francesco, who is 6. Originally from Treia, Italy, which is near Florence on the Adriatic coast, Del Poeta worked in a pizzeria when he was younger. He built a brick oven in his backyard, where he hosts neighbors and the families of his sons’ classmates. His favorite pizza, called Amir Pizza after a former talented postdoctoral student in his lab, is a white pizza with extra-thin-sliced white onions, one thin-sliced hard avocado, a generous portion of pistachios and mozzarella.
While the work Del Poeta does has clinical implications, he has no expectations to move to a biotechnology company. “I love what I do,” he said. “If I can make the life of a patient a little better, if I can bring a new drug to the clinic or even contribute a little bit to improve the survival of a patient, I would be so grateful.”
Readers who would like to know more about the battle against fungal infections can gather information at the Global Action Fund for Fungal Infections web site, www.gaffi.org.
(Copied from the Three Village Times)
Congratulations to Dr. Maria Ryan, New Vice President of the American Association for Dental Research
ICB&DD congratulates Dr. Dr. Maria Ryan for being elected the new Vice President of the American Association for Dental Research. Members of the American Association for Dental Research (AADR) have elected Dr. Maria Emanuel Ryan, professor and chair of the Department of Oral Biology and Pathology in the School of Dental Medicine at Stony Brook University, to serve as the next AADR vice president. Her term will begin at the conclusion of the 45th AADR Annual Meeting in Los Angeles, California, March 16-19, 2016. After serving as vice president, she will remain on the AADR Board of Directors for three consecutive terms as president-elect, president and immediate past president. AADR is the largest division of the International Association for Dental Research (IADR).
Dr. Ryan, who is a distinguished Stony Brook School of Dental Medicine alumna and a past president of the Stony Brook University Alumni Association, has served on the Board of Directors of the Task Force on Design and Analysis of Oral Health Research since 2003 and is a newly elected member of Cold Spring Harbor Laboratory Association Board. She received an AB from Barnard College, Columbia University; a DDS from the School of Dental Medicine, Stony Brook University; a certificate in periodontology from the School of Dental Medicine, University of Connecticut Health Center; and a PhD in Oral Biology and Pathology, Stony Brook University. She was a fellow of the Hedwig van Ameringen Executive Leadership in Academic Medicine Program for Women at Drexel University College of Medicine, and the Energeia Partnership, Academy of Regional Stewardship at Molloy College.
Ryan stated that she was honored to be elected the AADR vice president and that it will be a privilege to serve the AADR membership and contribute to the continued growth of the organization. “This is a proud and exciting time for the AADR as it is for the Department of Oral Biology and Pathology, known for its’ translational research,” she said. “I look forward to working together with my colleagues here at Stony Brook and throughout the nation to achieve high standards of excellence in oral health research, promoting the mission and advancing the vision of the AADR.”
“The School of Dental Medicine faculty, students and staff are quite honored and pleased that Dr. Ryan has been recognized for her achievements,” said Dr. Mary R Truhlar, dean of the School of Dental Medicine at Stony Brook University. “We wish her much success in this prestigious position.”
Ryan has been an AADR member since 1991. She has been an invited speaker and co-chaired numerous scientific sessions at IADR/AADR meetings. As an active member and volunteer, she has reviewed applications for the AADR Neal W. Chilton Fellowship in Clinical Research since the inception of the award. She served as president of the AADR New York/Long Island Section from 2000 to 2007 and on the AADR Council from 2001 to 2006. Additionally, she has been a reviewer for the IADR/AADR Journal of Dental Research. As vice president, Ryan will work to support the AADR mission and the vision of the Board of Directors.
Maria Ryan and her husband, Charles Ryan, a distinguished Stony Brook University alum, established the Ryan Endowed Scholarship for Future Academicians at the School of Dental Medicine in 2012. This is the second endowed scholarship the couple has created at Stony Brook. In 2002 the Ryan’s established the Charles and Maria Ryan Scholarship in Oral Biology and Pathology. (copied from the SBU news)
Congratulations to Dr. James Bliska, New Director of the Center for Infectious Diseases
ICB&DD congratulates Dr James Bliska for being elected unanimously by his colleagues to be the Director of the Center for Infectious Diseases. In this position, Jim will lead the Center into new and joint areas of research on infection involving several of its own investigators as well as other investigators from across the campus. The Center Director, along with the Department of Environmental Health and Safety, is responsible for the operations of the Biosafety Level III Laboratory that is used by scientists from several university departments. It was obvious to all of us who elected him that he was the logical person to head the Center. Jim received his BS in Bacteriology from UW Madison (1983), a PhD in Molecular Biology from the University of California at Berkeley (1988), and was a postdoctoral fellow at Stanford (1988-1993). He became an Assistant Professor in Molecular Genetics and Microbiology at Stony Brook in 1993, and was promoted to Professor in 2003. His laboratory carries out basic research on mechanisms of bacterial pathogenesis and host protection. He has recently expanded his talents into global health, especially in the area of functional evolutionary genomics of host-pathogen interactions, as they have developed in underdeveloped areas of the world. During his research career Jim has generated over 134 publications and has been continually funded by grants from the NIH, Department of Defense, PIVOT and other sources. Since 2003 Jim has been Director of an NIH T32 training grant for PhD students entitled "Molecular and Cell Biology of Infectious Diseases". He has mentored 10 PhD students, 7 postdoctoral fellows, numerous undergraduates, and is actively involved in teaching graduate level courses in microbiology, molecular biology, genetics, cell biology, chemical biology and microscopy. Jim's awards include PEW Scholar in the Biomedical Sciences (1994), Fellow of the American Academy of Microbiology (2012), Fellow of the American Association for the Advancement of Science (2013), and Dean’s Award for Excellence in Graduate Mentoring (2015). At the university level, Jim has served on the Institutional Biosafety Committee since 1995, including as Chair since 2006, and as a member of the Steering Committee for the Institute of Chemical Biology and Drug Discovery (2005-2015). Among his contributions to the broader scientific community, Jim served as Editor for Infection and Immunity (2003-2013), and since 2013 has been an Editor for PLoS Pathogens, a new premier journal for Microbiology. He is also serving (2013-2017) as a Standing Member of the NIH Microbiology and Infectious Diseases Research Committee study section.
Congratulations to Dr. James Bliska on his election to the position of Director of the Center for Infectious Diseases.
Dr. Huilin Li partners with BNL in Groundbreaking DNA Research
In a partnership with Stony Brook researchers, scientists at the U.S. Department of Energy’s Brookhaven National Laboratory have released the first-ever images of the protein complex that unwinds, splits, and copies double-stranded DNA. The electron microscope images offer new insight into how this molecular machinery functions, including new possibilities about its role in DNA “quality control” and cell differentiation. The images and implications are described in a paper published online by the journal Nature Structural & Molecular Biology, November 2, 2015. Rockefeller University scientists also worked in partnership with the project.
“This work is a continuation of our long-standing research using electron microscopy to understand the mechanism of DNA replication, an essential function for every living cell,” said Huilin Li, a biologist with a joint appointment at Brookhaven Lab and Stony Brook University. These new images show the fully assembled and fully activated ‘helicase’ protein complex-which encircles and separates the two strands of the DNA double helix as it passes through a central pore in the structure-and how the helicase coordinates with the two ‘polymerase’ enzymes that duplicate each strand to copy the genome.” Studying this molecular machinery, known collectively as a “replisome,” and the details of its DNA-copying process can help scientists understand what happens when DNA is miscopied-a major source of mutation that can lead to cancer-or learn more about how a single cell can eventually develop into the many cell types that make up a multicellular organism. But no one has produced a real structure of a replisome at any resolution for any organism until now. “All the textbook drawings and descriptions of how a replisome should look and work are based on biochemical and genetic studies,” Li said, likening the situation to the famous parable of the three blind men trying to describe an elephant, each looking at only one part. Those textbook drawings show the helicase moving along the DNA, separating the two strands of the double helix, with two polymerases located at the back where the DNA strand is split. In this configuration, the polymerases would add nucleotides (molecules containing the complementary A, T, G, and C bases of the genetic code) to the side-by-side split ends as they move out of the helicase to form two new complete double helix DNA strands.
To test these assumptions, Li’s group turned to the technique they had previously used to study individual components of the helicase, electron microscopy (EM). Jingchuan Sun, an EM expert in Li’s lab, was essential to the success of the work. He studied samples of replisomes from baker’s yeast cells-a model for all nucleus-containing cells-prepared and provided by Roxana Georgescu in Michael O’Donnell’s research group at Rockefeller University. O’Donnell’s group had previously published biochemical results related to this work. “DNA replication is one of the most fundamental processes of life, so it is every biochemist’s dream to see what a replisome looks like,” Sun said. “Our lab has expertise and a decade of experience using electron microscopy to study DNA replication, which has prepared us well to tackle the highly mobile therefore very challenging replisome structure. Working together with the O’Donnell lab, which has done beautiful functional studies on the yeast replisome, our two groups brought perfectly complementary expertise to this project,” he said. The team’s first-ever images of an intact replisome revealed that only one of the polymerases is located at the back of the helicase. The other is on the front side of the helicase, where the helicase first encounters the double-stranded helix. This means that while one of the two split DNA strands is acted on by the polymerase at the back end, the other has to thread itself back through or around the helicase to reach the front-side polymerase before having its new complementary strand assembled. The scientists were so surprised by this finding that they asked another group at Rockefeller, led by Brian Chait, to perform additional structural studies using mass spectrometry. Yi Shi, a postdoctoral fellow in Chait’s group performed this work, which confirmed the electron-microscopy-based conclusion about the unexpected architecture of the replisome.
The counterintuitive position of one polymerase at the front of the helicase suggests that it may have an unforeseen function. The authors suggest several possibilities including keeping the two “daughter” strands separate to help organize them during replication and cell division. It might also be possible that, as the single strand moves over other portions of the structure, some “surveillance” protein components check for lesions or mistakes in the nucleotide sequence before it gets copied-a sort of molecular quality control.
This architecture could also potentially play an important role in developmental biology by providing a pathway for treating the two daughter strands differently. Many modifications to DNA, including how it is packaged with other proteins, control which of the many genes in the sequence are eventually expressed in cells. An asymmetric replisome may result in asymmetric treatment of the two daughter strands during cell division-an essential step for making different tissues within a multicellular organism.
As the paper concludes, “Clearly, further studies will be required to understand the functional implications of the unexpected replisome architecture reported here.”
One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation for the State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit applied science and technology organization. (copied from the SBU news)
ICB&DD Ninth Annual Symposium
On Thursday, October 8, 2015, ICB&DD hosted its Ninth Annual Symposium entitled, “Molecular Targets, Chemoprevention, and Cancer Therapeutics” at the Charles B. Wang Center, Stony Brook University. The Symposium featured seven Plenary Lecturers. The event was well attended by a diversified audience composed of faculty, research staff and students on campus and Brookhaven National Laboratory, as well as universities and industries in the Greater New York metropolitan area. The Poster Session equally attracted a large participation of students from Stony Brook University, Stony Brook Cancer Center and Brookhaven National Laboratory among others. There were 59 scientific papers presented at the Poster Session. Dr. Kenneth Shroyer (Chair, Department of Pathology, Stony Brook School of Medicine), Chair of the Symposium Organizing Committee, opened the Symposium, and introduced Dr. Lina Obeid, Professor of Medicine and Vice-Dean for Scientific Affairs of Stony Brook School of Medicine, who gave the welcoming remarks for the Symposium. Then, Dr. Shroyer introduced Dr. Iwao Ojima, Distinguished Professor and Director of ICB&DD. Dr. Ojima concisely summarized the history of accomplishments and the current and future goals of ICB&DD.
Dr. John Haley, Associate Professor of Research, Department of Pathology, Stony Brook School of Medicine introduced the first Plenary Lecturer, Dr. Kowk-Kin Wong, Professor at Harvard Medical School, Dana-Faber Cancer Institute. Dr. Wong gave a lecture entitled, “Understanding Sensitivity and Resistance to Targeted Therapeutics and Immunotherapeutics Using Mouse Models of Lung Cancer”. In his presentation, Dr. Wong provided an overview of his research which focuses on understanding the pathogenesis and genetic alterations involved in lung tumorigenesis, as well as testing novel targeted cancer therapeutics in vivo in lung cancers. Dr. Wong proposed that the data generated from the “mouse clinical trials” that his research laboratory performed would provide the preclinical rationale for moving the therapeutic agents that his group used into human clinical trials. Dr. Geoffrey Girnun, Associate Professor, Department of Pathology, Stony Brook School of Medicine introduced the second Plenary Lecurer, Dr. Shaomeng Wang, Professor Internal Medicine and Pharmacology, University of Michigan Medical School. Dr. Wang gave a lecture entitled, “Building a Successful Drug Discovery Program in Academia”. In his presentation, Dr. Wang discussed the difficulty encountered in moving a drug discovery research project from the laboratory to its clinical development. His lecture provided an overview of his team’s efforts and collaborations with academic researchers and biotech and pharmaceutical partners to advance compounds into clinical development and its research aimed at the “discovery and identification of optimal compounds for clinical development”. Dr. Orlando Schärer, Professor of Pharmaceutical Sciences, Stony Brook University introduced the third Plenary Lecturer, Dr. Steven E. Rokita, Professor, Department Bioorganic Chemistry and Biochemistry, Johns Hopkins University who gave a lecture entitled, “Dynamic Alkylation and its Consequences for DNA”. In his presentation, Dr. Rokita described prior research on the mutagenic and therapeutic potential of DNA alkylation that focused almost exclusively on irreversible reactions in contrast to reversibly reacting intermediates that can continually maintain a distribution of products regulated by thermodynamics rather than kinetics. He stated that the ultimate goal of his research group is to develop covalent, but dynamic cross-linking agents that can run the DNA repair process sufficiently to enhance the potency of chemotherapy.
Dr. Kenneth Shroyer, introduced the fourth Plenary Lecturer, Dr. Rajesh Agarwal, Professor, Department of Pharmaceutical Sciences, University of Colorado Cancer Center. Dr. Agarwal gave a lecture entitled, “Colon Cancer Chemoprevention in New Era: Targeting the Initiators and the Initiated Ones, a Cancer Stem Cell Perspective”. In his presentation, Dr. Argarwal described the studies performed by his research group on whether sibilium, a non-toxic chemopreventive agent against Colorectal Cancer (CRC) has the potential to target colon CRC and associated inflammatory niche. He indicated that its studies “showed that sibilium strongly decreases the percentage of colonosphere formation (a stem cell characteristic) of CRC. Dr. Kenneth Shroyer introduced the fifth Plenary Lecturer, Dr. Patricia Thompson Carino, Professor, Department of Pathology, Stony Brook School of Medicine. Dr. Thompson-Carino gave a lecture entitled, “MicroRNAs, Colorectal Adenomatous Polyps and Cancer Risk”. In her presentation, Dr. Thompson-Carino focused on the deregulation of microRNAs in colorectal tumorigenesis across the adenoma to carcinoma continuum placing emphasis on the functional consequences at transition states between benign polyps and polyps that have a high risk of converting to colorectal cancer. In addition, she described recent results demonstrating microRNA patterns that accurately distinguish adenomatous polyps with a high propensity to convert to cancer from those with low malignant potential.
Dr. Isaac Carrico, Associate Professor, Chemistry Department, Stony Brook University introduced the sixth Plenary Lecturer, Dr. Ravi Chari, Executive Director, Chemistry & Biochemistry, ImmunoGen, Inc. Dr. Chari gave a presentation entitled, “Antibody-Drug Conjugates: From Concept to Clinical Validation”. In his presentation, Dr. Chari described his group’s research that is devoted to a semisynthetic approach to develop a panel of “linkable” analogs of matansine, a potent tubulin interacting plant natural product as well as potent DNA alkylators (IGNs) for use in Antibody-Drug Conjugates (ADCs). He indicated that multiple ADCs using maytansinoids are currently in clinical evaluation and that the clinical data that is emerging from this study is promising. Dr. Chari stated that, the recent approval by the FDA of the maytansinoid conjugate ado-trastuzumab emtansine (T-DMI) for the treatment of metastatic breast cancer validates the potential of this technology”. Dr. John Haley introduced the seventh Plenary Lecturer, Dr. Geoffrey Girnun. Dr. Girnun gave a presentation entitled, “Targeting Oncogenic Signaling in Cancer via Regulation of Metabolic Flux”. In his presentation, Dr. Girnun discussed the emerging studies that highlight the role of the TCA cycle in the regulation of cancer cell proliferation and previous studies of the role of Phosphoenolpyruvate carboxykinase (PEPCK) in glucogenesis and as a key regulator of TCA cycle flux. He described that his research team discovered that PEPCK has a role in promoting cancer cell proliferation in vitro and in vivo and also one in linking metabolic flux and anabolic pathways to cancer cell growth. Dr. Girnun concluded his lecture by stating that his research group is currently working on the study of inhibitors of PEPCK as therapeutic agents of cancer.
Dr. Shroyer gave the closing remarks, thanking the Plenary Lecturers for their outstanding presentations as well as the Organizing Committee members for its successful planning and execution of the Ninth Annual ICB&DD Symposium.
The best three posters of the 66 scientific papers presented in the Poster Session were selected for the Poster Awards. The award winning posters this year were Siyeon Lee from the laboratory of Dr. Iwao Ojima for her poster entitled, “Boc-Lys (AC)-GABA-taxoids as Novel Tumor Targeted Anticancer Agents”, Jingming Wang from the laboratory of Dr. Hyungjin Kim for her poster entitled, “Regulation of DNA Repair by the SCF Ubiquitin E3 Ligase Complex” and Lisa-Marie Nisbett from the laboratory of Dr. Elizabeth Boon for her poster entitled, “Characterization of a NosP Signal Transduction Pathway in Shewanella oneidensis”.
The 9th ICB&DD Symposium culminated with a wonderful dinner at the Chapel of the Charles B. Wang Center. Among the attendees were, Lina Obeid, Yusuf Hannun, Peter Tonge and John Haley. They expressed their appreciation for the outstanding lectures presented at the symposium and acknowledged the significance of the ICB&DD and the collaborative efforts among academia and industry. They also commended Dr. Ojima for his leadership of the ICB&DD and congratulated his 70th birthday. The Symposium was co-sponsored by the Office of the Vice-President for Research, Stony Brook School of Medicine, Department of Chemistry, Department of Pathology, Chembio Diagnostics Systems Inc., TargaGenix Inc.,
ICB&DD welcomes Dr. Maurizio Del Poeta as a new Member. Dr. Del Poeta is a Professor in the Department of Molecular Genetics and Microbiology at Stony Brook University. Dr. Del Poeta’s laboratory studies the function of sphingolipids involved in mediating signaling pathways and fungal pathogenesis. He has a particular interest in understanding the molecular mechanisms by which both, fungal and host sphingolipids, mediate the outcome of the interaction between fungal and mammalian cells. Dr. Del Poeta received his M.D. degree (1992) from University of Ancona, School of Medicine, Italy. He specialized in Infectious Diseases and performed a research fellowship (1992-1996) in the School of Medicine at the University of Ancona, Italy and in the Division of Infectious Diseases at Duke University Medical Center, Durham, NC (1995-1996). Soon after his research fellowship at Duke University, Dr. Del Poeta became an independent scientific investigator on aspects of lipid metabolism and how it regulates the pathogenicity of infectious diseases, a field that he contributed to pioneering. He became an Assistant Professor (1999-2005), Associate Professor (2006-2011), Professor (2011-2012) in the Departments of Biochemistry & Molecular Biology, and Microbiology & Immunology at the Medical University of South Carolina, Charleston, SC. Throughout the years, his research has been supported by the National Institute of Health, the US Department of Defense, the US Department of Education, the Burroughs Wellcome Fund, the American Heart Association and the Department of Veteran Affairs Medical Center. Dr. Del Poeta recently initiated the research and development of new antifungals discovered in his laboratory. Together with Dr. Ojima at the Institute of Chemical Biology and Drug Discovery and with Dr. Fries in the Division of Infectious Diseases, Dr. Del Poeta secured a large NIH grant to further study this new class of antifungals, which are urgently needed for our patients. Dr. Del Poeta’s expertise will extensively strengthen the ICB&DD Infectious Diseases Research Program.
Stony Brook Symposium Celebrating the Achievements of Professor Ojima on the Occasion of His 70th Birthday
On June 5-6, 2015, a special symposium, Chemical Synthesis in Life Sciences was held at the Charles B. Wang Center, to celebrate the achievements of Professor Iwao Ojima, Distinguished Professor and Director of the Institute of Chemical Biology and Drug Discovery (ICB&DD), on the occasion of his 70th birthday. There were 230 registered attendees, including speakers, alumni, students, faculty and staff. This two-day Symposium featured 30 plenary, keynote and invited speakers who were all alumni of the Ojima Research Laboratory. The Symposium had five sessions, covering Medicinal Chemistry and Chemical Biology, Drug Design, Discovery and Development, Chemistry and Multifaceted Career Development, Organic Synthesis and Synthetic Methods and Chemical Synthesis in Industries. In addition, there were Opening Lecture by Professor Makoto Fujita, The University of Tokyo and Closing Lecture by Professor Ojima, as well as Poster Sessions with 50 poster presentations. Full Symposium Program is available in the following link.
Day one of the symposium was followed by the Symposium Reception and Banquet in the ballrooms of the Student Activities Center with 130 guests. At the Banquet, the volume 1 booklet of the dedicated papers to Professor Ojima was presented by Dr. Tadashi Honda, Director of the ICB&DD’s Anti-inflammatory Research Laboratory. Professor Ojima presented an after-dinner talk, entitled “Memorable Moments in the Three Decades of Life at Stony Brook", which is available in the following link.
Also, the group photos of the Ojima Research Laboratory members since 1984 to 2014, which were shown during the Banquet, are available in the following link.
Day two of the symposium was concluded with the Farewell Reception at the Theater Lobby of the Charles B. Wang Center. The Symposium was sponsored by the following firms: ImmunoGen, Inc., Crystal Brook Music International, Kimberly-Clark Corp., Merck & Co., Cytokinetics, Inc., Ajinomoto Pharmaceuticals Co., Hamari Chemicals Ltd, Tosoh F-Tech, Inc., Fujian Yew Park Biological Co. Ltd., Wilmerhale LLP, Reata Pharmaceuticals, Department of Chemistry and ICB&DD.
The Symposium photos are available in the following link.
ICB&DD Congratulates Dr. Huilin Li, ICB&DD member and Professor of Biochemistry Department, for receiving a NIH high-end instrumentation grant ($2M) for Stony Brook. The grant will be used to purchase a 200 kV cryo-EM, a direct electron detector, and a volta phase plate. The new cryo-EM facility will be installed on the ground floor of the Center for Molecular Medicine, adjacent to the new 850 MHz NMR probes. Recent advance in cryo-EM equipment, particularly in direct electron detection and novel computational algorithm, has enabled cryo-EM to solve atomic or near atomic resolution structures of many proteins and their complexes, all with only a minuscule amount of sample and without the need for crystallization. In addition to revealing the structure-function of key biological machines, cryo-EM method is being actively used by structural biologists around the world to investigate drug-target complexes, such as the microtubule-stabilizing agents, proteasome inhibitors, and many membrane receptors and transporters.
ICB&DD faculty receive NIH funds for state-of-the-art instrument for drug screening
A team of 15 ICB&DD faculty research groups received $204,000 in federal funding from the National Institutes of Health to set up a molecular screening system at Stony Brook. Projects that will benefit from this instrument include development of new antibiotics, pain therapies and targeted anti-cancer therapies.
The GE Healthcare Life Sciences Biacore T200 surface plasmon resonance instrument is a state-of-the-art instrument to detect binding of drug-like molecules to target proteins. The instrument will be housed in the proteomics core facility in the Health Science Center where it will be used to determine the affinity and rate of ligand binding. This new technology enables the complete cycle for rational structure-based drug development at Stony Brook.
Three dimensional structures of drug targets can be determined at Stony Brook with ultra-high field 850 MHz and 700 MHz NMR instrumentation as well as the robotic crystal screening facility and access to the National Synchrotron Light Source II at Brookhaven National Lab – one of the brightest and most advanced X-ray sources in the world. Large libraries of small molecule compounds can be screened for binding to the three dimensional structures of drug targets through support by world leaders in method development for computational docking procedures, force field development and mathematical methods. The T200 instrument can be used to experimentally characterize lead candidates which can be optimized by medicinal chemists in the ICB&DD medicinal chemistry groups.
ICB&DD welcomes Dr. Chia-Shin (Lori) Chan as a Project Member. Dr. Chia-Hsin (Lori) Chan is an Assistant Professor, Department of Pharmacological Sciences, School of Medicine, Stony Brook University. Dr. Chan’s research program includes (a) Delineation of the network of metabolic reprogramming in tumor initiation and progression, (b) Exploration of regulatory machinery orchestrating EMT-driven glycolysis or EMT as new therapeutic interventions. Dr. Chan received her Ph.D. (2007) in biochemistry and molecular biology from the National Taiwan University in Taiwan. Her graduate studies focused on transcriptional and post-transcriptional regulation of eukaryotic gene expression, using retroviruses as a model system. She was a Postdoctoral Research Fellow under the mentorship of Hui-Kuan Lin in the Department of Molecular and Cellular Oncology, M. D. Anderson Cancer Center, Houston, Texas. Dr. Chan was the recipient of several awards including Breast Cancer SPORE Career Development Award, The Harold C. and Mary L. Daily Endowment Fellowship Award, Susan G Komen Postdoctoral Fellowship Award and Odyssey Outstanding Research Publication Awards, M.D. Anderson Cancer Center. Dr. Chan’s research would surely strengthen the Cancer Research Program.
ICB&DD welcomes Dr. Geoffrey Girnun as a member. Dr. Girnun is an Associate Professor of the Department of Pathology and Director of Cancer Metabolomics, School of Medicine, Stony Brook University. His research is focused on linking fundamental aspects of metabolism and diseases such as diabetes and cancer. In particularly, on metabolic regulators and their role in disease. Currently his lab is focused on metabolic alterations in disease with a strong emphasis on PPARg co activator 1 (PGC1a), a master regulator of multiple metabolic functions. He is currently using transgenic approaches to knockout out PGC1a in specific tissues to determine its role in cancer and metabolic diseases. Dr. Girnun received his Ph.D. in free radical and radiation biology, from the University Of Iowa College Of Medicine. He was a Postdoctoral Research Fellow and later an Instructor, in the Department of Cell and Cancer Biology, at Harvard Medical School and Dana-Farber Cancer Institute (1999-2003). He became an Assistant Professor of the Department of Biochemistry and Molecular Biology at the University Of Maryland School Of Medicine (2007-2013). Dr. Girnun was the recipient of several awards including the Madeline Franchi Ovarian Cancer Fund Award, NIH K01 Award, Individual National Research Service Award, NIDDK, and Carver Medical Research Trust Award. Dr. Girnun’s expertise will significantly strengthen the ICB&DD's Cancer Research Program.
ICB&DD welcomes Dr. Hyungjin Kim as aproject member. Dr. Kim is an Assistant Professor of the Department of Pharmacological Sciences, School of Medicine, Stony Brook University. Dr. Kim received his Ph.D. in Molecular Cell Biology (2009) from Washington University in St. Louis, MO. He was a research postdoctoral fellow (2010-2014) in the Department of Radiation Oncology at Dana-Farber Cancer Institute, Harvard Medical School under the mentorship of Dr. Alan D. D’Andrea, M.D. Dr. Kim’s research focuses on the Fanconi anemia DNA interstrand cross-link repair and Translesion DNA synthesis DNA damage tolerance mechanism, to better understand the signaling pathways of DNA repair and how their defects are associated with tumorigenesis. His research complements Dr. Sharer's program on DNA damage/repair, and would strengthen the Cancer Research Program.
ICB&DD congratulates Professor Iwao Ojima. He has been named a Fellow of the National Academy of Inventors (NAI)
(Copied from the SBU news)
STONY BROOK, N.Y., December 16, 2014 – Iwao Ojima, PhD, SUNY Distinguished Professor in the Department of Chemistry, and Director of the Institute of Chemical Biology & Drug Discovery (ICB&DD) at Stony Brook University, has been named a Fellow of the National Academy of Inventors (NAI).
According to the NAI, election as an “NAI Fellow” is “a high professional distinction accorded to academic inventors who have demonstrated a prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development and the welfare of society.” Dr. Ojima and other new 2014 NAI Fellows will be inducted on March 20, 2015, as part of the 4th Annual Conference of the NAI at the California Institute of Technology in Pasadena.
“Professor Ojima has had a highly distinguished career as an educator, researcher and inventor at Stony Brook,” said Samuel L. Stanley Jr., MD, President of Stony Brook University. "His work in medicinal chemistry and chemical biology has led to important discoveries, contributing to the betterment of society. I am so pleased to see his many accomplishments recognized by this distinguished academy."
“Dr. Ojima has distinguished himself as a world-renowned scholar and inventor with outstanding contributions to a broad range of chemical sciences,” said Benjamin Hsiao, PhD, a Professor in the Department of Chemistry, Affiliated Professor in Materials Science & Engineering, and Founding Director of the Innovative Global Energy Solutions Center at Stony Brook University. “His work at Stony Brook has impacted global research and discovery in the areas of organic, organometallic, fluorine medicinal and pharmaceutical chemistry, as well as chemical biology and drug discovery, with multifaceted interfaces with chemistry, biology and medicine.”
A faculty member in Chemistry at Stony Brook since 1983, Dr. Ojima has been granted more than 100 patents. The Research Foundation for the State University of New York has filed more than 80 of these patents globally on his behalf.
Additionally, since 2004 his leadership as Director of the ICB&DD has brought interdisciplinary and multidisciplinary research bridging the physical sciences, biological sciences, biomedical engineering and various School of Medicine departments together, along with expertise from Brookhaven National Laboratory, to tackle significant biomedical problems and find solutions, including the discovery of novel therapeutic drugs. During these 10 years, the ICB&DD has received more than $40 million in research grant funding to advance discoveries.
Dr. Ojima’s many contributions to medicinal chemistry and chemical biology include: the discovery and development of a new generation of taxoid anticancer agents, which possess excellent anticancer activity against drug-resistant cancer cells and tumors; the development of fluorine-containing taxoids as excellent probes for the identification of bioactive conformations of paclitaxel and taxoids; the creation of highly efficacious taxoid conjugates with monoclonal antibodies, omega-3 fatty acids, and vitamins for tumor-targeting cancer chemotherapy; and the discovery and development of novel anti-tuberculosis agents targeting bacterial cell division protein.
“I am honored to receive this esteemed distinction as an NAI Fellow,” said Dr. Ojima. “We will continue to promote our sprit of innovation and invention at Stony Brook and through multidisciplinary collaborative research ventures at the ICB&DD, with the goal of discovering and developing new and efficacious therapeutic drugs to treat challenging diseases.”
SUNY Provost and Executive Vice Chancellor Alexander N. Cartwright was also named a 2014 NAI Fellow.
“Groundbreaking, impactful research conducted by our faculty and students across New York State is an incredible source of pride for SUNY as we aim to drive knowledge and innovation in a global economy,” said SUNY Chancellor Nancy L. Zimpher. “Congratulations to Dr. Cartwright and Dr. Ojima on this distinct honor from the NAI. This honorable recognition is a testament not only to their outstanding work but to the innovation ecosystems that SUNY campuses foster in every region.”
More About Distinguished Professor Dr. Iwao Ojima
Iwao Ojima received his B.S. (1968), M.S. (1970), and Ph.D. (1973) degrees from the University of Tokyo, Japan. He joined the Sagami Institute of Chemical Research and held a position as Senior Research Fellow until 1983. He joined the faculty at the Department of Chemistry, State University of New York at Stony Brook first as Associate Professor (1983), was promoted to Professor (1984), Leading Professor (1991), and then to University Distinguished Professor (1995). He served as the Department Chairman from1997 to 2003. He serves as the founding Director for the Institute of Chemical Biology and Drug Discovery (ICB&DD) at Stony Brook from 2003. Also, he was a Visiting Professor at the Université Claude Bernard Lyon I, France (1989), The University of Tokyo, Japan (1996), The Scripps Research Institute, La Jolla, CA (1997), and Université de Paris XI, BIOCIS, Châtenay-Malabry, France (1997).
His research interests include medicinal chemistry and chemical biology (anticancer agents, tumor-targeted drug delivery, antibacterial agents, enzyme inhibitors), catalytic asymmetric synthesis, organic synthesis by means of organometallic reagents and catalysts, peptidomimetics, b-lactam chemistry (applications of the beta-lactam synthon method), and organofluorine chemistry (fluoroamino acids and peptides, fluorotaxoids, medicinal applications). He has published more than 400 papers and reviews in leading journals and more than l00 patents issued (33 US patents), edited 8 books (SciFinder lists >850 publications to his credits; Google Scholar indicates total citation number of >19,500 as of September 2014), and he has given more than 120 Plenary and Invited Lectures in international conferences and symposia by September 2014.
He is a recipient of the Arthur C. Cope Scholar Award (1994), the E. B. Hershberg Award (for important discovery of medicinally active substances) (2001) and the ACS Award for Creative Work in Fluorine Chemistry (2013) from the American Chemical Society; The Chemical Society of Japan Award (for distinguished achievements) (1999) from the Chemical Society of Japan; Outstanding Inventor Award (2002) from the Research Foundation of the State University of New York. He was inducted into the Medicinal Chemistry Hall of Fame, American Chemical Society (2006). He is a Fellow of the J. S. Guggenheim Memorial Foundation (1995-), the American Association for the Advancement of Science (1997-), The New York Academy of Sciences (2000-), and the American Chemical Society (2010-).
He has served in various advisory committees for National Institutes of Health (National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences), National Science Foundation and the U.S. Department of Energy. He has served as a member of the Executive Committee for the Division of Organic Chemistry and the Long Range Planning Committee for the Division of Medicinal Chemistry, American Chemical Society.
He has served and has been serving as Editorial Advisory Board member of Journal of Organic Chemistry, Organometallics, Journal of Molecular Catalysis, Current Topics in Medicinal Chemistry (current), Medicinal Chemistry (current), Letters in Drug Design & Discovery (current), Bulletin of the Chemical Society of Japan (current), and Anti-Cancer Agents in Medicinal Chemistry (current). He has also served as the Guest Editor for thematic issues of the Journal of Medicinal Chemistry, Accounts of Chemical Research, and Current Topics in Medicinal Chemistry. In addition, he serves as the Senior Editor of “Future Medicinal Chemistry.”
Additional Quotes from Stony Brook faculty:
“Dr, Ojima has for many years been one of Stony Brook University’s leading faculty in technology transfer and innovation in the biomedical realm,” said David O. Conover, Interim Vice President for Research. “He is richly deserving of this award, and I congratulate him on this outstanding career achievement.”
“One of Stony Brook’s most prolific inventors, Dr. Ojima has developed numerous new chemical entities that have the potential to be efficacious therapeutics for cancer and infectious disease,” said Peter Donnelly, Director of the Office of Technology Licensing and Industry Relations. “Dr. Ojima has worked closely with our office and industry to successfully foster commercial partnerships to translate his discoveries into therapeutic modalities.”
“I am delighted that Dr. Ojima is being inducted into the NAI,” said Nicole Sampson, Professor and Chair of the Department of Chemistry. “He is the fourth Stony Brook Chemistry faculty member inducted into the NAI. This recognition illustrates the centrality of chemistry for the translation of fundamental research into applications that benefit humanity.”
ICB&DD Members attended the 2014 CIBR 1st International Symposium of Chemistry and Life Sciences
GATHERING IN JIANGYIN, Speakers, organizers, and guests at the ACSCIBR symposium included Corey (front row, fifth from left) and Zhou (back row, sixth from left). Participating in the ACS-CIBR symposium as speakers, organizers, and guests are (front row, left to right) James J. Chou, Harvard Medical School; Wuyi Meng, CIBR; Shaomeng Wang, University of Michigan; Peng Wang, Yabao Pharmaceutical Group; Corey; Li He Zhang, Peking University; William J. Greenlee, MedChem Discovery Consulting; Iwao Ojima, Nicole S. Sampson, and Peter J. Tonge, all with Stony Brook University, SUNY; and John J. Piwinski, JJPiwinski Pharma Consulting. Back row, left to right: Zhijie Chang, Tsinghua University; Hong Shen, Roche Innovation Center Shanghai; Jiaquan Wu and Liang Zhu of CIBR; Haijun Zhang, Biortus; Zhou; Duan Liu, WuXi AppTec; Lan He, National Institutes for Food & Drug Control; Yali Chen, CIBR; and Steven Hill, ACS Office of International Activities.
The ACS International Chemical Sciences Chapter in Shanghai put on a winner with the 1st International Symposium of Chemistry & Life Sciences, held on Oct. 16–17 in Jiangyin, in Jiangsu province, China. With about 125 attendees, the meeting highlighted the challenges and opportunities in drug discovery for cancer and infectious diseases. An international slate of speakers, led by Nobel Laureate and Harvard University emeritus chemistry professor E. J. Corey, described trends and new approaches to discovering drugs for cancer and infectious diseases. “Infectious diseases and cancer are two major disease classes in China,” said Jingye Zhou, a principal scientist at the Lilly China R&D Center and the chair of the ACS Shanghai chapter. “The symposium shone some light on the R&D work that could help patients in China and worldwide.” The chapter partnered with the E. J. Corey Institute of Biomedical Research (CIBR), in Jiangyin, in organizing the meeting. CIBR is a nonprofit research organization nominally founded by Corey and a group of Chinese returnees and funded by the Jiangyin local government and Jiangsu province. Its mission is to make a difference in the treatment and diagnosis of disease, specifically tuberculosis. In presenting a “superoverview” of cancer, Corey described the disease as caused by cascading dysregulation when things go wrong in the highly ordered, very low entropy system that is the human body. “Cancer is an inevitable condition because of the imperfections of the body transiting from one state to another,” he said. “If we all were to live to a very old age and had otherwise perfect health, we would die of cancer.” The ultimate advance—the real prize—he said, is rapid methods for early diagnosis. The symposium was “excellent” and “very interesting,” Corey told C&EN. “The folks in Jiangyin are delighted to have a connection with ACS. They see ACS as a premier organization that gives them a link to the outside world.” “Many scientists in China are unable to attend ACS national meetings due to logistic hurdles,” Zhou told C&EN. “By creating a local ACS organized symposium, we brought topnotch scientific exchange to a broad community in China. The symposium also enabled local ACS members to network with each other and with international speakers.” (Copied from C&EN)
ICB&DD 8th Annual Symposium
(from left to right), Drs. Iwao Ojima, Alan D’Andrea, Barry Stoddard, Vincent Yang, Miguel Garcia Diaz, Cynthia Burrows, Thomas Tuschl, Chuan He and Orlando Schärer
On Thursday, October 9, 2014, ICB&DD hosted its eighth ICB&DD Annual symposium entitled, “Frontiers in Genome Sciences” at the Charles B. Wang Center, Stony Brook University. The symposium featured seven Plenary Lecturers. Two of the lecturers, Dr. Dr. Miguel Garcia-Diaz and Dr. Vincent Yang represented Stony Brook University. The event was well attended by a widely ranging audience composed of faculty, research staff and students on campus and Brookhaven National laboratory, as well as universities and industries in the Greater NY metropolitan area. The Poster Session equally attracted a large participation of students from Stony Brook University, Stony Brook Cancer Center, Cold Spring Harbor Laboratory, Columbia University and Memorial Sloan-Kettering Cancer Center among others. There were 66 scientific papers presented at the Poster Session. Dr. Orlando Schärer, Professor of Pharmacological Sciences, Stony Brook University and Chair of the Symposium Organizing Committee, opened the symposium, and introduced Dr. Yusuf Hannun, Professor of Medicine and Director, Stony Brook Cancer Center, and Vice-Dean for Cancer Medicine, Stony Brook University School of Medicine, who gave welcome remarks for the Symposium. Then, Dr. Schärer introduced Dr. Iwao Ojima, Distinguished Professor and Director of ICB&DD. Dr. Ojima concisely summarized the history of accomplishments, and the current and future goals of ICB&DD.
Dr. Nicole Sampson, Professor and Chair, Department of Chemistry, Stony Brook University introduced the first Plenary Lecturer, Dr. Cynthia J. Burrows, Distinguished Professor, University of Utah. Dr. Burrows gave a lecture entitled, “Shape-Shifters: How Promoter and Telometric DNA Sequences Respond to Oxidative Stress”. In her presentation, Dr. Burrows provided an overview of her research that indicates that “oxidative stress in the cell results in modifications to DNA and RNA bases and downstream events including effects on transcription and replication as well as signaling for repair. Ultimately unrepaired damage in DNA leads to mutagenesis that is a contributing factor to cancer and other diseases”. Dr. David Green, Associate Professor, Department of Applied Mathematics and Statistics, Stony Brook University introduced the second Plenary Lecturer, Dr. Barry Stoddard, Principal Investigator, Fred Hutchinson Cancer Research Center. Dr. Stoddard gave a lecture entitled, “Structure, Engineering and Application of Targeted Nucleases for Genome Engineering and Correction”. In his presentation, Dr. Stoddard discussed the approaches that are now being used in the rapidly maturing discipline of genome engineering and targeted gene modification “in which genomes within cell lines, tissues or organisms are manipulated and altered at specific individual loci”.
Dr. Elizabeth Boon, Associate Professor, Department of Chemistry, Stony Brook University introduced the third Plenary Lecturer, Dr. Chuan He, Professor, The University of Chicago and Investigator, Howard Hughes Medical Institute. Dr. He gave a lecture entitled, “Reversible DNA and RNA Methylation and Biological Regulation”. In his presentation, Dr. He stated that, “we have developed chemical and biochemical methods to precisely map and study active DNA demethylation in mammalian systems,” and as a result of the use these techniques, his research team’s “discoveries indicate the presence of a new mode of biological regulation that depends on reversible RNA modification”. Dr. Orlando Schärer introduced the fourth Plenary Lecturer, Dr. Alan D. D’Andrea, Professor, Harvard Medical School and Scientific Director, Division of Genomic Stability and DNA Repair, Dana Faber Cancer Institute. Dr. D’Andrea gave a lecture entitled, “Fanconi Anemia/BRCA Pathway and its control by Ubiquitination”. “Fanconi Anemia (FA) is a rare autosomal recessive X linked recessive cancer susceptibility disorder characterized by bone marrow failure, congenital malformations, and cellular hypersensitivity to Cisplatin, Mitomycin C, and other crosslionking agents”. Dr. D’Andrea’s lecture focused “on the specific roles of Ubiquitin and SUMO in the regulation of the Fanconi Anemia/BRCA pathway”. genesis that is a contributing factor to cancer and other diseases”.
Dr. Kenneth Shroyer, Professor and Chair, Department of Pathology, Stony Brook University introduced the fifth Plenary Lecturer, Dr. Vincent W. Yang, Professor and Chairman, Department of Medicine, Stony Brook
University School of Medicine. Dr. Yang gave a lecture entitled, “Intestinal Stem Cells: Dynamics and Regulation”. In his presentation, Dr. Yang reviewed the recent literature regarding how proliferation and lineage determination of Lgr5-expression intestinal stem cells (ISC) is regulated. He also discussed “the roles of a number of transcription factors called Krüppel-like factors (KLFs), in regulating proliferation and differentiation of ISC in the intestinal epithelium”.
Dr. Jessica Seeliger, Assistant Professor, Department of Pharmacological Sciences, Stony Brook University introduced the sixth Plenary Lecturer, Dr. Miguel Garcia-Diaz, Associate Professor, Department of Pharmacological Sciences, Stony Brook University School of Medicine. Dr. Garcia-Diaz gave a lecture entitled, “Mechanisms of Mitochondrial Transcription and Mitochondrial Disease”. In his presentation, Dr. Garcia-Diaz described the extensive evidence that “links mitochondrial deficiencies to human pathology, with defects in gene expression playing a central role in pathogenesis.” His research team has “been studying the regulation of mitochondrial transcription, its association with ribosome biogenesis and how defects in transcriptional termination can contribute to mitochondrial disease”. Dr. Jingfang Ju, Associate Professor, Department of Pathology, Stony Brook University introduced the seventh Plenary Lecturer, Dr. Thomas Tuschl, Professor, The Rockefeller University and Investigator, Howard Hughes Medical Institute. Dr. Tuchl gave a lecture entitled, “RNA Regulation and DNA Diagnostics”. In his presentation, Dr. Tuschl discussed his research group’s “experimental approaches for studying RNA-binding proteins (RBPs) and defining their target RNAs and how these can be guided by their census”.
Dr. Schärer gave the closing remarks, thanking the Plenary Lecturers for their outstanding presentations as well as the Organizing Committee members for the successful planning and execution of the 8th Annual ICB&DD Symposium.
There were 66 scientific papers presented in the Poster Session. The best three posters were selected for the Poster Awards. Historically, there have been two but the best poster for the medicinal chemistry category was awarded this year. The award-winning posters this year were: Lingling Jiang from the laboratory of Robert Rizzo. Grace Tan from the laboratory of Markus Seeliger and Weixuan Yu for the medicinal chemistry category from the
laboratory of Peter Tonge.
The 8th ICB&DD Symposium culminated with a splendid dinner at the Chapel of the Charles B. Wang Center. Among the attendees were, Lina Obeid (Vice-Dean of Research, Stony Brook University School of Medicine), Maria Ryan (Chair, Department of Oral Biology and Pathology) and John Haley (Professor of Research, Department of Pathology and Director of Proteomics, former Senior Research Director of Translational Research, OSI Pharmaceuticals). They expressed their appreciation for the outstanding lectures presented at the Symposium. Equally they acknowledged the high level of importance of ICB&DD collaborative efforts among academia and industry. They all congratulated Dr. Ojima for his numerous contributions and successful leadership of the ICB&DD. This year, as part as commemorating 8 years of remarkable success of these annual symposia, Dr. Ojima presented a “Glass Flame of Appreciation” to every chair of the organizing committee since its inauguration from 2007. The flame of appreciation awards were presented to Drs. James Bliska, Daniel Raleigh, Nicole Sampson, Maria Ryan, Peter Tonge, Todd Miller, Robert Haltiwanger and Orlando Scharer. A “Glass Flame of Appreciation” was also presented to Ms. Roxanne Brockner, Assistant to the Director of ICB&DD. Dr. Ojima cited her crucial contributions to the success of ICB&DD, and particularly big applauses were given to her distinction. The Symposium was co-sponsored by, Office of the Vice-President for Research, Stony Brook University School of Medicine, Department of Chemistry and Chem-Master International Inc.
Stony Brook Researchers Quantify Underlyinglandscape of Cancer
The cellular and genetic hallmarks of cancer development are multiple, and a team of researchers in the Departments of Chemistry and Physics at Stony Brook University have developed a pictorial yet quantitative landscape theory to explore cancer cellular development that could form the foundation to new anticancer tactics. Their research and methods used are published in two new scientific papers. One is published in the Proceedings of the National Academy of Sciences (PNAS) early edition and titled “Landscape and flux reveal a new global view and physical quantification of mammalian cell cycle,” and the other is published in the Journal of the Royal Society Interface and titled “Quantifying the underlying landscape and paths of cancer.” In the PNAS paper, the researchers considered one of the hallmarks of cancer – the cell cycle. The cell cycle speed of cancer is much faster than normal cells. By quantitatively uncovering the landscape of the cell cycle, the researchers are able to visualize the cell cycle progress and illustrate its journey along a “ring valley” with hills and valleys. By showing this unconventional view of the cell cycle quite different from standard texts, they discovered two major forces for the cell cycle: the cycle flux as the driving force originated from the nutrition supply for accelerating cell cycle and the barriers from the “hills and valleys” as the dragging force for decelerating cell cycle. “By identifying two cell cycle driving forces, and the key genes and regulations influencing these forces, we believe this could be the basis for an anti-cancer targeting strategy that targets these key genes and regulations, as well as the nutrition supply to reduce the cell cycle speed from fast cancer back to normal cell speed,” explained Prof. Jin Wang, PhD, a faculty member in the Department of Chemistry, an adjunct faculty member in the Department of Physics, and a member of the Laufer Center for Physical and Quantitative Biology, and a member of the Institute of Chemical Biology and Drug Discovery. In the Journal of the Royal Society paper, the research team developed a global potential landscape and path framework to quantify cancer and associated processes, all of which involves the interaction of genes. In this conceptual and quantitative picture, the cancer and normal cells can be viewed as different basins of a landscape. The landscape topography characterizes important biological states, such as normal, cancer, and cancer cell proliferation. “In this case we are uncovering multiple hallmarks of cancer, not just one, and with that we can identify the key genes and regulations determining the depths of cancer and normal basins as well as the transition barriers in between,” said Professor Wang. “The landscape shape can be used as a potential way to design anti-cancer strategies by targeting multiple genes and gene regulation patterns.” Prof. Wang, and his Stony Brook post-doctoral researcher and co-author Dr. Chunhe Li of the Department of Chemistry, along with scientific collaborators in China will continue the research in order to build and refine quantitative models of the cellular landscape of cancer. The combined research is supported by the National Science Foundation and the National Science Foundation of China. (copied from the SBU news)
ICB&DD congratulates Dr. Scott Laughlin for receiving a National Science Foundation Award for Brain Initiative Research. The National Science Foundation (NSF) has awarded Dr. Scott Laughlin, an Early Concept Grant for Exploratory Research (EAGER). The EAGER awards are part of the foundation’s support of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a multi-agency research effort that seeks to accelerate the development of new neurotechnologies that promise to help researchers answer fundamental questions about how the brain works. In March of this year, NSF asked researchers to submit ideas for early-stage, potentially ground-breaking new approaches to reveal how neuronal processes in the brain lead to complex behaviors in any organism. NSF reviewed the summaries and invited full proposals from applicants whose ideas best aligned with the outlined research topics. Dr. Laughlin, ICB&DD Project Member and Assistant Professor in the Department of Chemistry at Stony Brook, was among 36 recipients of these EAGER awards. Each EAGER award is for $300,000 over a two-year period, and award recipients will apply this funding to develop a range of conceptual and physical tools, from real-time whole brain imaging, to new theories of neural networks, to next-generation optogenetics. Dr. Laughlin will apply the grant funds to an investigation of the use of synthetic molecules for mapping the connections between neurons in the brain. See more at: http://sb.cc.stonybrook.edu/news/general/2014-08-25-sbu-professor-receives-nsf-eager-award-for-brain-research.php
ICB&DD welcomes Dr. Jarrod French as a Project Member. Dr. French is an Assistant Professor in the Department of Biochemistry and Cell Biology as well as Department of Chemistry. Dr. French utilizes a highly interdisciplinary approach to study the structure, function and control of enzymes and enzyme complexes involved in cellular metabolism. His research particularly focuses in understanding how multi-protein macromolecular machines provide spatial and temporal control over metabolic pathways in cells. The long term goal of his research is to characterize the structure, functions and control mechanisms of these protein assemblies and to exploit this information to develop novel treatments for cancer and inflammatory diseases such as rheumatoid arthritis. He has employed a variety of techniques including X-ray crystallography, mechanistic enzymology, microscopy and chemical biology. After completing an undergraduate degree (2004) with a double major in chemistry and biology from Brock University (St. Catharines, Ontario, Canada), Dr. French received his MS (2007) in Biomedical Sciences and his Ph.D. (2010) in Chemical Biology from Cornell University, NY. He was the recipient of a Canadian Institutes of Health Research Postdoctoral Fellowship and completed his postdoctoral research fellowship in the laboratory of Dr. Stephen Benkovic in the Department of Biochemistry at the Pennsylvania State University (2011-2013). Dr. French has an exceptionally strong background in chemical biology, mechanistic enzymology and macromolecular crystallography. He was recently recruited through the Biomolecular Imaging Cluster Hire. Dr. French will be an excellent addition to the cancer and anti-inflammatory research programs as well as the chemical biology training program.
ICB&DD welcomes Dr. Steven Glynn as a Project Member. Dr. Glynn is an Assistant Professor in the Department of Biochemistry and Cell Biology. Dr. Glynn’s research uses x-ray crystallography, mechanistic biochemistry and protein design techniques to uncover the operating principles of energy-dependent proteolytic machines in mitochondria. The main goal of his research is to understand, on a molecular level, how mitochondrial energy-dependent proteases select specific protein targets, and the nature of the mechano-chemical coupling that drives dislocation, translocation and ultimately, degradation. Such knowledge will shed light on the general operating principles of the diverse family of AAA+ machines. Dr. Glynn received his Ph.D. (2005) in Molecular Biology and Biotechnology from the University of Sheffield, Sheffield, United Kingdom. He completed his postdoctoral research training in the laboratory of Professor Robert T. Sauer in the Department of Biology at the Massachusetts Institute of Technology (2006-2010). Dr. Glynn’s research has been published in high quality scientific journals. He will be an excellent addition to cancer and infectious diseases research programs, as well as chemical biology training program.
ICB&DD welcomes Dr. Martin Kaczocha as a Project Member. Dr. Kaczocha is an Assistant Professor in the Department of Anesthesiology, School of Medicine, Stony Brook University. Dr. Kaczocha’s research focuses on fatty acid binding proteins: novel targets for the development of anti-inflammatory and antinociceptive drugs. Dr. Kaczocha received his Ph.D. (2009) in Biochemistry and Molecular Biology. His graduate studies focused on the role of fatty acid binding proteins and FAAH-2 in endocannabinoid uptake and inactivation. He received his bachelor in sciences in Pharmacology with honors from Stony Brook University. Dr. Kaczocha was the recipient of several awards including the Howard Hughes Medical Institute Postdoctoral Teaching Fellowship and NIH Research Training Fellowship. His current research program seeks to develop fatty acid binding protein inhibitors as novel antinociceptive and anti-inflammatory drugs. This research is part of a multi-investigator project of ICB&DD funded by the National Institutes of Drug Abuse (NIDA). Dr. Kaczocha will be an excellent addition to the anti-inflammatory research program, as well as chemical biology training program.
From the Lab Bench to the Computer
Brian Ralph ’15 combines two approaches to researching innovative pain medication
A passion for both science and math has been a boon for undergraduate Brian Ralph, catapulting him to the crossroads of a major multidisciplinary research project. Since joining the team at theInstitute for Chemical Biology and Drug Discovery (ICB&DD) at Stony Brook, Brian has worked with researchers in Biochemistry and Cell Biology, Chemistry, Applied Mathematics and Statistics, and Anesthesiology to develop new pain medications that will work by elevating the levels of natural painkillers in the body. “It’s a great group,” says Brian, a member of the Honors College who is a biology major with a concentration in quantitative biology and bioinformatics — in his words “a bit of a crossover between biology and math.” Now a junior, Brian has been working in Dale Deutsch’s biochemistry lab since his freshman year. Deutsch, Professor of Biochemistry and Cell Biology in the College of Arts and Sciences, and his associates are studying new classes of inhibitors that temporarily stop the action of Fatty Acid Body Proteins (FABPs) present in our cells. The result of this inhibition is an artificial elevation in the natural painkillers — called endocannabinoids — that exist in our bodies. Drugs that may eventually be developed from this research will not be addictive, which is a common problem with the opioids now widely used.
Last month, the ICB&DD received a $3.8 million grant from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to continue its groundbreaking work. Led by Principal Investigator Deutsch, other members of the team include Iwao Ojima, Distinguished Professor of Chemistry and Director of the ICBⅅ Martin Kaczocha, a former post-doctoral fellow in Deutsch’s lab who is now an Assistant Professor in the Department of Anesthesiology; Robert Rizzo, Associate Professor of the Department of Applied Mathematics and Statistics; Bill Berger, a PhD candidate in Ojima’s lab; Huilin Li, a biochemist in both the Department of Biochemistry and Cell Biology and at Brookhaven National Lab; and the Laufer Center for Quantitative and Physical Biology.
To tackle the project from another direction, Brian also works in Rizzo’s lab using software that allows him to visualize and manipulate the FABP protein structures in three-dimensional space. “Different laboratories have different approaches to the same research,” explains Brian. “In Dale’s lab we take a biological approach, and here it’s more of a computational or structural approach.”
In December 2012 Brian co-authored a paper based on the team’s research with Berger and Koczocha in PlosOne. He is also co-author, along with Kaczocha, of a second paper submitted to PlosOne for review. Brian started doing research when he was a student at Smithtown High School West as part of Stony Brook’s Simons Summer Research Program, when he worked with Alan Turner in the Department of Anatomical Sciences. His work in the Deutsch lab has been supported by URECA and a Harvard Lyman award. Brian is a member of both the Undergraduate Biochemistry Society and the Undergraduate Biology Advisory Board.
With the goal of becoming a dentist, Brian is also active in Stony Brook’s Pre-dental Society and has shadowed pediatric dentists and oral surgeons. Will he combine research and dentistry someday? “That’s still up to debate,” says Brian. “I love dentistry. It’s something that’s become very close to me. And while I wish to pursue dentistry, I definitely want to continue with research in the future because it has been such a big part of my life.” In his spare time, Brian plays the cello in Stony Brook’s undergraduate orchestra. He also enjoys cycling and running and is training for a triathlon next spring. “In the end, I would love to live a modest life as a dentist,” he says. “Something where I’d be able to enjoy my life and what I do every day. I’d also like to be able to contribute to the ongoing questions in science and research as part of a lab. And, of course, someday I would love to see Stony Brook’s FABP inhibitor on the market. “You never know. Five, ten years from now, maybe we’ll have advances that can put it through clinical trials, and we’ll see where it goes from there. I’d love to see our whole lab group — the ICB&DD’s — name on a pain inhibitor, something as common as aspirin, hopefully.” (copied from the SBU news by Toby Speed.)
ICB&DD welcomes Dr. Scott T. Laughlin as a Project Member. Dr. Laughlin is an Assistant Professor in the Department of Chemistry. Dr. Laughlin’s research uses chemistry to examine how the brain works. How does the brain sense the environment? How does it decode that sensory information and control behavior? All of the brain’s many functions rely on its neural circuits—a complex web of neurons connected to each other in such a way that they can perform the logical operations that allow us to think, respond to stimuli, etc. Precisely how neural circuits perform their calculations is a mystery whose solution has wide ranging implications for human health. Using organic synthesis, molecular biology, and behavioral neurobiology, he creates chemical tools to help reveal the structure of neural circuits in living animals. Dr. Laughlin’s received his Ph.D. (2008) in Chemistry and Chemical Biology from University of California, Berkeley. He completed his postdoctoral research fellowship in the Department of Molecular and Cell Biology at University of California, Berkeley in the laboratory of Professor John Ngai (2008-2013). Dr. Laughlin has an exceptionally strong background in chemistry and neuroscience. He is exploring the interface of chemistry and neurobiology, i.e., "chemical neurobiology". He is one of the "Chemical Biology Initiative" hires at the Chemistry Department and started this past September. Dr. Laughlin will be an excellent addition to the Chemical Biology Training Program and will lead the establishment of Chemical Neurobiology Program at ICB&DD.
ICB&DD welcomes Dr. Ming-Yu Ngai as a Project Member. Dr. Ngai is an Assistant Professor in the Department of Chemistry. Dr. Ngai’s research focuses on developing novel and practical synthetic methodologies to address unmet challenges in organic synthesis and medicinal chemistry, and (ii) identifying and developing new radiotracers for Positron Emission Tomography (PET) imaging to elucidate disease mechanisms, identify drug targets, assess treatment efficacy, and accelerate drug discovery and development. Dr. Ngai’s research interests are multidisciplinary, covering organic and organometallic chemistry, photochemistry, radiochemistry, and biomedical imaging. Dr. Ngai received his Ph.D. (2008) in Chemistry from University of Texas, Austin. He was awarded a Croucher Foundation Postdoctoral Research Fellowship at Stanford University and worked in the laboratory of Professor Barry M. Trost (2009-2011). He also performed postdoctoral research at Harvard University in the laboratory of Professor Tobias Ritter (2011-2013). Dr. Ngai has an exceptionally strong background in chemical synthesis and will apply it to molecular imaging for diagnosis and therapy. He is one of the "Chemical Biology Initiative" hires at the Chemistry Department and started this past September. Dr. Ngai will be an excellent addition to cancer and infectious diseases research programs, as well as chemical biology training program.
Congratulations to the ICB&DD team, consisting of Drs. Dale Deutsch (PI) Department of Biochemistry, Iwao Ojima (Co-PI) Department of Chemistry, Robert Rizzo (Co-PI) Department of Applied Mathematics and Statistics, Huiling Li (Co-PI) Department of Biochemistry and Martin Kaczocha (Co-PI) Department of Anesthesiology, School of Medicine on receiving a research award from the National In
stitutes of Health, National Institute of Drug Abuse. This ICB&DD multidisciplinary research team has received a five-year $3.8 million grant for the project entitled “Anandamide Transport Inhibitors”. The main focus of this grant is to develop new drugs, inhibiting recently discovered anandamide transporter, for pain, stress and issues with drug addiction and withdrawal. Anandamide is a neurotransmitter that occurs naturally throughout the body for regulation of pain and stress. This is a very exemplary multi-disciplinary research project of productive collaborative efforts among faculty and ICB&DD. Initial funding for the research began with a SBU-BNL seed grant to Dr. Deutsch and Dr. Li from Stony Brook University and Brookhaven National Laboratory in 2010, followed by a Stony Brook University School of Medicine Targeted Research Opportunities (TRO) Fusion award to Drs. Deutsch, Li, and Ojima as well as a New York State SUNY REACH grant for Drs. Deutsch and Haj-Dahmane. Dr. Deutsch also received a previous single investigator grant from the NIH to research FABPs. - See more at:
ICB&DD 7th Annual Symposium
(from left to right) Drs. Jonathan Rudick, Miguel Garcia-Díaz, Iwao Ojima, Nicole Sampson, Linda Hsieh-Wilson, David Green, Geert-Jan Boons, Gerard Hart, Jeffery Esko and Richard Cummings
On Friday, October 11, 2013, The ICB&DD hosted its seventh ICB&DD Annual Symposium entitled, “Frontiers in Glycosciences and Chemical Biology” at the Charles B. Wang Center, Stony Brook University. The symposium featured seven Plenary Lecturers. Two of the lecturers, David Green and Nicole Sampson represented Stony Brook University. The event was very well attended by a widely ranging audience composed of faculty, research staff and students on campus and Brookhaven National Laboratory, as well as universities and industries in the greater NY metropolitan area. The Poster Session equally attracted a large participation of students from Stony Brook University, New York University, Columbia University, Chembio Diagnostic Systems Inc, and Brookhaven National Laboratory among others. There were 82 scientific papers presented at the Poster Session.
Dr. Robert Haltiwanger, Chair of the Symposium Organizing Committee, opened the Symposium, and introduced Dr. Bejamin Hsiao, Vice President for Research at Stony Brook University, who gave welcome remarks for the Symposium. Then, Dr. Haltiwanger introduced Dr. Iwao Ojima, Distinguished Professor and Director of ICB&DD. Dr. Ojima concisely summarized the history of accomplishments, current and future goals of ICB&DD.
Dr. Haltiwanger, Professor and Chair of Cell Biology and Biochemistry, introduced the first Plenary Lecturer, Dr. Gerald Hart, Professor and Director of Biological Chemistry, Johns Hopkins University School of Medicine. Dr. Hart gave a lecture entitled, “Nutrient Regulation of Signaling & Transcription: Roles of O-GlcNAcylation in Diabetes, Cancer and Neurodegeneration”. He presented an excellent overview of his research program on understanding how dynamic O-GlcNAcylation serves as a major sensor of cellular nutrient status and how it regulates transcription, signaling and metabolism in response to nutrients.
Dr. Jonathan Rudick, Assistant Professor of Chemistry introduced the second Plenary Lecturer, Dr. Geert-Jan Boons, Professor, Department of Chemistry, University of Georgia. Dr. Boons gave a lecture entitled, “Glycoscience: Downsizing or Oversizing?” His presentation described a chemoenzymatic strategy that can provide libraries of highly complex asymmetrical N-glycans
Dr. Wei-Xing Zong, Associate Professor of Molecular Genetics & Microbiology introduced the third Plenary Lecturer, Dr. Jeffery Esko, Professor, Department of Molecular and Cellular Medicine, University of California at San Diego. Dr. Esko gave a very stimulating lecture entitled, “Heparin Sulfate: Light at the End of the Chain”. In his presentation, Dr. Esko focused on the need for improved biomarkers for differential diagnosis, prognosis and monitoring of therapeutic interventions for mucopolysaccharidoses (MPS).
Dr. Elizabeth Boon, Associate Professor of Chemistry introduced the fourth Plenary Lecturer, Dr. Nicole Sampson, Professor and Chair, Department of Chemistry, Stony Brook University. Dr. Sampson gave a lecture entitled, “Mycobacteria on Steroids: Metabolite Profiling and Enzyme Function”. She described the identification of two new structural-functional enzyme motifs in Mycobacterium tuberculosis (Mtb) for the catalysis of b-oxidation with steroid substrates in the igr operon that function in the metabolic pathway for sterol side chain cleavage in the metabolism of cholesterol.
Dr. David Green, Associate Professor of Applied Mathematics and Statistics introduced the fifth Plenary Lecturer, Dr. Richard Cummings, Professor and Chair, Department of Chemistry, National Center for Functional Glycomics, Emory University School of Medicine. Dr. Cummings’ lecture was entitled, “Genetic and Biochemical Insights into Roles of Glycoconjugates in Animal Biology and Disease”. Dr. Cummings presented how the use of both genetic and biochemical approaches has enabled him and his team to explore the roles of glycoconjugates in a variety of biological systems, including animal development and cancer, as well as innate and adaptive immune responses.
Dr. Miguel Garcia-Diaz, Associate Professor of Pharmacology introduced the sixth Plenary Lecturer, Dr. David Green, Associate Professor, Department of Applied Mathematics and Statistics, Stony Brook University. Dr. Green’s presentation was entitled, “Rational Engineering of Anti-Viral Lectins Targeting HIV”. In his lecture, Dr. Green indicated that viral surfaces are able to avoid an immune response because their surfaces are heavily glycosylated. He indicated that his team’s understanding of the origins and affinities of a series of oligosaccharides is evolving and his team has developed computational models that explain the known differences in affinities for a series of oligosaccharides and provide insight into the mechanisms of multi-valent bonding.
Dr. Isaac Carrico, Associate Professor of Chemistry introduced the seventh Plenary Lecturer, Dr. Linda Hsieh-Wilson, Professor Division of Chemistry and Chemical Engineering, California Institute of Technology and the Howard Hughes Medical Institute, Pasadena, California. Dr. Hsieh-Wilson’s presentation was entitled, “The Sweeter Side of Cellular Signaling: Elucidating the Structure-Function Relationships of Carbohydrates in the Brain”. In her stimulating presentation, Dr. Hsieh-Wilson described the fundamental challenges in studying carbohydrates and the development of chemical approaches to overcome these challenges. She exemplified how the principles and tools of chemistry can be used to elucidate the roles of carbohydrates and their associated proteins in development and neuroregeneration.
Dr. Haltiwanger gave the closing remarks, thanking the Plenary Lecturers for their outstanding presentations as well as the Organizing Committee members for the successful planning and execution of the 7th Annual ICB&DD Symposium.
There were 82 scientific papers presented at the Poster Session. The best two posters were selected for the Poster Awards. The award-winning posters this year were: Sajjad Hossain from the laboratory of Elizabeth Boon in Department of Chemistry and Julie-Ann Cavallo from Department of Pharmacological Sciences, Stony Brook School of Medicine.
The 7th ICB&DD Symposium culminated with a splendid dinner at the Chapel of the Charles B. Wang Center. Among other attendees were Dr. Benjamin Hsiao, Vice-President for Research, Dr. Nicole Sampson (Chair, Department of Chemistry), Maria Ryan (Chair, Department of Oral Biology and Pathology) and Dr. Michael Frohman (Chairman, Department of Pharmacological Sciences, SOM). They expressed their appreciation for the outstanding lectures presented at the Symposium. Equally, they acknowledged the high level of importance of ICB&DD collaborative efforts among academia and industry. They all congratulated Professor Ojima for his numerous contributions and successful leadership of the ICB&DD. The symposium was co-sponsored by the Office of the Vice President for Research, Office of the Provost, School of Medicine, Department of Chemistry, Department of Biochemistry and Cell Biology, Forest Laboratories Inc. and Chem-Master International, Inc.
ICB&DD welcomes Mr. Andreas G. Grill as new Advisory Board Member. Mr. Grill is the Executive Director for Pharmaceutical Research & Development at Forest Research Institute, a subsidiary of Forest Laboratories, Inc. Mr. Grill is an executive leader with over twenty years of experience in the pharmaceutical industry. He is company appointed Global Project Development Team Leader responsible for global drug development and executive direction from conception through marketing registration. As a corporate business development team member, Andreas is responsible for maintaining partner relationships and representing Forest Laboratories as member of multiple Joint Steering Committees with several major business partners (US and ex-US). Moreover, Mr. Grill has extensive experience with implementing and leading pharmaceutical research & development departments that include functional areas of biopharmaceutics, formulation development, analytical development, preformulation, bioanalytical & drug metabolism, regulatory CMC and project management. Mr. Grill has held scientific and leadership positions at Pfizer, Forest Laboratories and Forest Research Institute. Mr. Grill’s versatile experience encompasses the development of a broad range of pharmaceutical dosage forms which transverse multiple indications. This versatility contributes to an impressive negotiation record with several domestic and international development partners as well as multiple divisions of the Food and Drug Administration and various Health Authorities worldwide. Mr. Grill is responsible for contributing to a significant number of pharmaceutical drug product approvals within the United States and worldwide. The products within Mr. Grills impressive portfolio include Lexapro®, Namenda®, Campral®, Combunox®, Bystolic®, Savella®, Namenda XR®, Teflaro™, Daliresp™ and Linzess™. Mr. Grill is an appointed Member of the Bioscience Advisory Board for SUNY Farmingdale and an appointed Member of the Board of Directors for the Farmingdale College Foundation. In addition, Mr. Grill volunteers as an Advisor for the BioStrategy Sessions at SUNY Stony Brook – Center of Biotechnology. Mr. Grill holds a Bachelor of Science in Biochemistry from the State University of New York at Stony Brook with graduate studies in Pharmacology/Toxicology at Saint John’s University and a Master of Business Administration from Dowling College.
6th ICB&DD Annual Symposium
(from left to right) Drs. Holger Sondermann, David Lawrence, Bonnie Bassler, Deborah Hung, Iwao Ojima, Elizabeth Boon, Jeffery Kelly and Todd Miller.
On Friday, October 12, 2012, The ICB&DD hosted its Sixth ICB&DD Annual Symposium, “Frontiers in Chemical Biology and Drug Discovery” at the Charles B. Wang Center at Stony Brook University. The symposium featured seven Plenary Lecturers. Two of them were from Stony Brook University. The event was very well attended by a wide range of audience from faculty, research staff and students on campus as well as universities and industries in the greater NY metropolitan area and Brookhaven National Laboratory. The Poster Session equally attracted a large participation of students from Stony Brook University, New York University, Columbia University, Chembio Diagnostic Systems Inc, and Brookhaven National Laboratory among others. There were 78 scientific abstracts presented at the Poster Session.
Dr. Todd Miller, Professor and Chair of the Symposium Organizing Committee, opened the Symposium and introduced Dr. Iwao Ojima, Distinguished Professor and Director of ICB&DD. Dr. Ojima concisely summarized the history of accomplishments, current and future goals of the ICB&DD. Dr.Elizabeth Boon, Assistant Professor of Chemistry introduced the first Plenary Lecturer, Dr. Bonnie BasslerHoward Hughes Medical Institute Investigator and the Squibb Professor of Molecular Biology at Princeton University, Member of the National Academy of Sciences. Dr. Bassler gave a lecture entitled “Manipulating Quorum Sensing to Control Bacterial Pathogenecity” . She explained the focus of her research on understanding how cell-cell communication in bacteria involves the production, release and subsequent detection of chemical signaling molecules named autoinducers. A process called quorum sensing. Research is now targeted in the development of therapies that interfere with quorum sensing to control bacterial virulence. Dr. Daniel Raleigh, Professor of Chemistry introduced the second Plenary Lecturer, Dr. Jeffery Kelly, Chairman, Department of Molecular and Experimental Medicine, Department of Chemistry, the Scripps Research Institute. Dr. Kelly gave a lecture entitled “Biological and Chemical Approaches to Adapt Proteostasis to Ameliorate Protein Misfolding and Aggregation Diseases”. His presentation focused on how the proteostasis network can be adapted through unfolded protein response arm-selective signaling to alleviate several loss-of-function diseases where excessive misfolding and degradation leads to maladies like the lysosomal storage diseases. Dr. James Bliska,Professor of Microbiology, introduced the third Plenary Lecturer, Dr. Holger Sondermann, Dr. Sondermann gave a very stimulating lecture entitled “The ins and outs of c-di-GMP Signaling in Bacterial Biofilm Formation”. In his presentation, Dr. Sondermann focused on the molecular mechanisms that yield finely tuned signaling cascades controlling cell adhesion in several bacterial species. In addition, how in the long term, the results emerging from these studies could provide blueprints for the development of novel therapeutics against bacterial infections. Dr. Stanley Zucker, Professor of Medicine, introduced the fourth Plenary Lecturer, Dr. Basil Rigas, Professor of Medicine and Pharmacological Sciences. Chief, Divisions of Cancer Prevention and Gastroenterology, Dean for Clinical Affairs, Stony Brook University School of Medicine. Dr. Rigas gave a lecture entitled “Modified NSAIDs and Cancer”. He presented an overview of his research on cancer prevention and its emphasis on the development of novel anticancer agents. He discussed how epidemiological studies and interventional trials have established NSAIDs as efficacious chemopreventive agents against several human cancers. Their drawbacks are low efficacy and significant side effects. To overcome these limitations, he has developed a general approach through which targeted chemical modifications of NSAIDs enhance their efficacy and minimize their toxicity. Dr. Jessica Seeliger, Assistant Professor of Pharmacological Sciences introduced the fifth Plenary Lecturer, Dr. Deborah Hung, Physician Scientist, Center for Computational and Integrative Biology, and Department of Molecular Biology, Massachusetts General Hospital; Department of Microbiology and Immunobiology, Harvard Medical School; Broad Institute of MIT and Harvard University. Dr. Hung’s lecture was entitled “Chemical Biological Approach to TB: Identifying New Drugs Targets”. Dr. Hung explained the focus of her research in how she is combining chemical biology and genomic approaches to define host-pathogen interactions and to reveal essential in vivo gene functions of pathogens to explore new paradigms for anti-infective intervention. By deploying small organic molecules and genome-wide tools to both perturb and understand bacterial infection, she is working to provide insight into new approaches to a variety of devastating pathogens, including Vibrio cholerae, Pseudomonas aeruginosa and Mycobacterium tuberculosis.
Dr. Peter Tonge, Professor of Chemistry introduced the sixth Plenary Lecturer, Dr. Elizabeth Boon, AssistantProfessor of Department of Chemistry, Stony Brook University. Dr. Boon’s gave a lecture entitled “Nitric Oxide Signaling in Bacteria: Discovery of a new Mechanism for regulating Bacterial Group Behavior”. She described her studies on the importance of nitric oxide (NO) as biological signals and its signaling role in bacteria. NO has also been implicated in processes such as quorum sensing and biofilm formation. Biofilms are extremely resistant to antibiotic treatments and responsible for approximately 60 percent of all human infections. Dr. Todd Miller, Professor of Physiology and Biophysics introduced the seventh Plenary Lecturer, Dr. David Lawrence, Professor, Division of Medicinal Chemistry & Natural Products, School of Pharmacy & Department of Chemistry, University of North Carolina at Chapel Hill. Dr. Lawrence presented a lecture entitled “Organic Chemistry at the Edge of Biology: Taming Cell Behavior with Light Responsive Molecules”. His very informative lecture provided a comprehensive view of the challenges associated with the design, synthesis, and use of light-responsive bioreagents, the scope and limitations associated with the instrumentation required for their applications, and a few recent examples used to scrutinize the secrets of cell signaling and behavior. Dr. Miller gave the closing remarks, thanking the Plenary Lecturers for their outstanding presentations as well as the Organizing Committee members for the successful planning and execution of the 6th Annual ICB&DD Symposium.
There were 78 scientific abstracts at the Poster Session. The best two posters were selected for the Poster Awards. The award-winning posters this year were by Dr. Kanishk Kapilashrami from the laboratory of Dr. Peter Tonge, Department of Chemistry, Esam Al-Shareffi from the laboratory of Dr. Robert Haltiwanger, Department of Biochemistry and William J. Allen from the laboratory of Dr. Robert Rizzo, Department of Mathematics and Statistics at Stony Brook University.
The 6th ICB&DD Symposium culminated with a splendid dinner at the Chapel of the Charles B. Wang Center. Among other attendees were Dr. Nicole Sampson (Chairman, Department of Chemistry), Dr. Michael Frohman (Chairman, Department of Pharmacological Sciences, SOM) and Anil Duhndale (Executive Director of the Long Island High Technology Incubator (LIHTI) and Stony Brook University Business Incubators). They expressed their appreciation for the outstanding lectures presented at the Symposium. Equally, they acknowledged the high level of importance of ICB&DD collaborative efforts among academia and industry. They all congratulated Professor Ojima for his numerous contributions and successful leadership of the ICB&DD. The symposium was cosponsored by the Office of the Vice President for Research, Office of the Provost, School of Medicine Office of Scientific Affairs, Department of Chemistry, Forest Laboratories Inc. and Chem-Master International, Inc.
ICB&DD congratulates Dr. Iwao Ojima for being named as the recipient of the 2013 American Chemical Society (ACS) Award for Creative Work in Fluorine Chemistry! Dr. Ojima is cited “for his outstanding contributions to fluorine chemistry through his pioneering and creative research in synthetic methodology and biomedical applications.” Dr. Ojima’s research, a combination of both transition metal catalysis and medicinal chemistry, has had a profound impact on the fluorine chemistry at the biomedical interface. This is his third ACS National Award in addition to the Arthur C. Cope Scholar Award (organic chemistry) in 1994 and the E. B. Hershberg Award (drug discovery and medicinal chemistry) in 2001, illuminating the exceptional breadth and excellence in his research. Dr. Ojima first introduced catalytic processes into organofluorine chemistry in the early 1980s, and developed highly-efficient methods for the practical synthesis of optically active fluoro-amino acids by means of catalysis and enzymatic resolution. His invention of a highly efficient process for the synthesis of 5-trifluoromethyluracil was commercialized for the production of trifluridine (antiviral drug). He developed successful fluorine-containing molecules for the treatment of high blood pressure and as pain killers. Most recently, he synthesized taxol derivatives containing fluorine as anticancer agents, probes of chemical and structural biology, and to enhance drug potency. Dr. Ojima will receive his award at the American Chemical Society Meeting in New Orleans, Louisiana, April 7-11, 2013, and will also present an award address at the Biennial Winter Fluorine Conference in St. Pete Beach, Florida, January 13-18, 2013.
ICB&DD has acquired a new mass spectrometer from Agilent Technologies for the Analytical Chemistry Laboratory. The new Agilent LC-UV-TOF was acquired in the summer of 2012. The instrument consists of a 1260 uPLC, a TOF mass analyzer and a UV-Vis diode-array detector (DAD). The DAD provides wavelength measurements from 190-800nm with a 20Hz acquisition rate. The mass spectrometer is a G6224A oaTOF model. It provides MS capabilities in the range m/z=100-20,000. It is typically operated in MS mode in the range m/z=100-3200 while maintaining a resolution of 20,000 at m/z= 1,522 and acquiring 20 spectra/sec with an accuracy of <2 ppm. The instrument has two possible ionization sources: 1) an ESI source and 2) a MultiMode source consisting of combined ESI and APCI ionization modes. Both sources have dual inlets allowing for internal reference mass calibration to achieve <2ppm mass accuracy. The instrument is used exclusively for accurate mass determination, formula verification (HRMS) and sample purity analysis for small molecules and biopolymers. The new Agilent LC-UV-TOF is located in Room 570 of the ICB&DD Analytical Chemistry Laboratory. The acquisition of this instrument was made possible by a generous research support from the Reata Pharmaceuticals to ICB&DD through Dr. Honda (Director, ICB&DD Anti-inflammatory Research Laboratory) and a matching fund from the SBU Office of the Vice-President for Research.
ICB&DD congratulates Dr. James Bliska for being elected Fellow of the American Academy of Microbiology. The American Academy of Microbiology is the honorific leadership group of the American Society for Microbiology (ASM), the world’s oldest and largest life science organization. Academy Fellows are eminent leaders in the field of microbiology and are relied upon for authoritative advice and information on critical issues in microbiology. Fellows are elected through a highly selective peer review process based on their records of scientific achievement and original contributions that have advanced microbiology. Dr. Bliska, who joined the Department of Molecular Genetics and Microbiology in 1993, investigates molecular mechanisms that underlie the pathogenesis of bacteria, particularly in regard to host-microbe cell interactions in the genus Yersinia. Discoveries in his laboratory have led to advances in the fields of bacterial pathogenesis and cell biology. Dr. Bliska pioneered work on a specialized bacterial toxin secretion mechanism that is now referred to in microbiology as type III secretion, a significant finding to help broaden the research field known as cellular microbiology. He invented an approach used to identify host cell targets of a bacterial toxin, a unique technological advancement widely adopted by other researchers. Dr. Bliska also discovered that host cells have innate immune mechanisms that can detect bacterial toxin secretion, a finding of general importance in the field of immunology. Dr. Bliska and other newly elected fellows nationwide were recognized at the annual ASM General Meeting in San Francisco, California on June 19, 2012
ICB&DD welcomes Dr.Yusuf Hannun as new Advisory Board Member. Dr. Hannun is the new Director of the Stony Brook Cancer Center and Vice Dean for Cancer Medicine, SOM SBU. Dr. Hannun is a renowned molecular biologist and physician-scientist who came to Stony Brook from the Medical University of South Carolina (MUSC) where he was Deputy Director of MUSC’s Hollings Cancer Center. Under Dr. Hannun’s leadership, the Hollings Cancer Center, a National Cancer Institute (NCI)-designated Cancer Center, was established at MUSC in 2009. Dr. Hannun’s research area of expertise focuses on investigating the molecular mechanisms of cancer, in particular, lipid mediators of cancer cell signaling. Dr. Hannun and colleagues discovered the signaling functions of these lipids and the vital roles they play in the cancer disease process, and cancer therapy, as well as in other areas of biomedicine such as neurobiology, inflammation, and metabolism. Dr. Hannun earned his M.D. degree with distinction in 1981 from the American University in Beirut, Lebanon. At the American University he completed an internship and residency in Internal Medicine. In 1986 he moved to the United States to serve a fellowship in Hematology and Oncology at Duke University. At Duke he rose to become the Wayne Rundles Professor of Oncology, the Director of the Program in Molecular Medicine, and Associate Director of the Duke Comprehensive Cancer Center. As the Director of the Stony Brook Cancer Center, Dr. Hannun will oversee a program that includes 12 site-specific, multidisciplinary disease management teams that are dedicated to diagnosing and treating patients with breast, colorectal, gastrointestinal, hematological, pediatric cancers, and all other types of cancers. He will also oversee research programs conducted within the School of Medicine that supports the disease management teams.
ICB&DD would like to welcome Dr. Huilin Li as a new Project Member. Dr. Li is a Professor in the Department of Biochemistry and Cell Biology at Stony Brook University and has a joint appointment as a Biophysicist in the Biology Department of Brookhaven National Laboratory. The major goal of Dr. Li's research is to understand the function of biological macromolecules via structural analyses, primarily by cryo-electron microscopy (Cryo-EM). Cryo-EM is capable of revealing low to medium resolution structures of large protein complexes that are proven difficult for X-ray crystallography or NMR methods. Dr. Li’s other research interests include: Structural basis of eukaryotic DNA replication initiation,the M. tuberculosis proteasome pathway and structural biology of membrane protein assemblies. He received his Ph.D in Electron Crystallography from University of Sciences and Technology, Beijing, China in 1994, and performed his postdoctoral research at the Lawrence Berkeley National Laboratory (1994-1998) and was appointed as a Project Scientist there (1998-2002). He joined the Biology Department at Brookhaven National Laboratory in 2002, first as an Associate Biophysicist and was promoted to Biophysicist with tenure (2002-2010). Then, he joined Stony Brook University in 2010. Dr. Li will be an excellent addition to the Structural Biology Program and the Infectious Research Program as well as other ICB&DD activities.
ICB&DD welcomes Dr. Anilkumar Dhundale as new Advisory Board Member. Dr. Dhundale is the Executive Director of the Long Island High Technology Incubator (LIHTI) and Stony Brook University Business Incubators. He is also an Adjunct Professor of the Department of Biomedical Engineering at SBU. Dr. Dhundale earned his B.S. in Chemistry from Queens College of CUNY in 1970, and spent 12 years at North Shore-LIJ as a medical technologist and then supervising an Automated Clinical Chemistry Laboratory. He earned M.S. degree in Clinical Chemistry from C.W. Post of Long Island University in 1976 and Ph.D. in Molecular Biology from SBU in 1987. In 1987-1998, Dr. Dhundale was involved in the development of diagnostic and research products, and in multiple aspects of drug discovery and technology development atOSI Pharmaceuticals LLC. He served as the Director for Scientific Affairs at the Center for Biotechnolgy at SBU in 1998-2008. Dr. Dhundale’s research interests are in commercialization of technology, i.e.- translating research discoveries into useable commercial products. These products can be therapeutics to treat disease, diagnostics for identifying or classifying disease, or tools for researchers to use. But in addition, all technology based products include Information Technologies, Clean/ Alternative Energy, etc. In 2008, Dr. Dhundale was appointed as the Executive Director of LIHTI, manages the Stony Brook Technology Business Incubators Program, assisting academic researchers to start companies as well as mentoring established small technology businesses, all with a goal to translate discoveries into novel products and services. LIHTI’s ultimate goal for economic development is to create and retain high technology jobs and have positive economic impact in the Long Island region.
ICB&DD would like to welcome Dr. Kenneth Dill as Advisory Board Member. Dr. Dill is the Director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University and Professor of the Department of Physics and Astronomy as well as the Department of Chemistry. Dr. Dill is a member of the National Academy of Sciences and a past president of the Biophysical Society. He is well known internationally for his pioneering work on the physical forces that give rise to the structures and properties of protein molecules. Dr. Dill came to Stony Brook University in 2010 and was named the founding Director of the Laufer Center for Physical and Quantitative Biology. The main goals of Dr. Dill’s research in the Laufer Center are (i) to better understand the physical principles of biology and study the physics of proteins, biological cells, and water; (ii) to develop methods in statistical physics and computational biology. Dr. Dill received his S.B, S.M. (1971) in mechanical engineering from the Massachusetts Institute of Technology. He received his Ph.D. (1978) in Biology from the University of California at San Diego and performed postdoctoral research (1981) in chemistry at Stanford University. Prior to his appointment at Stony Brook, he was at the University of California at San Francisco (1982-2010) where he rose to the rank of Distinguished Professor of Pharmaceutical Chemistry and Biophysics and Associate Dean of Research in the School of Pharmacy
ICB&DD-Sanofi Collaboration on TB Drug Discovery and Development
From left to right: Dr. Peter Tonge, Provost Dennis Assanis, Deputy Vice-President for Research Nancy Daneau, Sanofi Associate Vice President, Head of Infectious Disease Research, Dr. Laurent Fraisse, Sanofi Medicinal Chemistry Partnership Manager, Infectious Disease Unit, Dr. Gilles Courtemanche, Distinguished Professor IwaoOjima, Office of Sponsored Programs Manager, Lydia Chabza and Sean Boykevisch, Licensing Associate, Office of Technology Licensing
Stony Brook University and Sanofi have announced amulti-year research collaboration with an option to a world-wide license to compounds resulting from the ICB&DD Director, Dr. Ojima’s work on FtsZ inhibition as a potential treatment for Tuberculosis (TB) and other bacterial infections. TB is a lethal and highly contagious infectious disease caused by Mycobacterium tuberculosis. TB is second only to HIV as the most deadly infectious disease. TB is transmitted through the air and may lay dormant in the body in a latent state. It is estimated that one third of the world’s population is infected with latent TB and approximately 12 million people suffer from active infection. Once active, TB is spread through the air by coughing and sneezing. TB is treated with a cocktail of antibiotics over the course of 6 months or more, making it a long, complicated and difficult to follow treatment regimen. Not adhering to the treatment course can lead to the development of multiple drug resistant TB (MDR-TB). Therefore, new drug targets and treatments are needed to shorten treatment times and improve reatment outcomes. Dr. Ojima and his team at ICB&DD have discovered novel compounds that inhibit bacterial cell division by interfering with a critical cellular protein called FtsZ. The FtsZ is responsible for forming a contractile ring within the bacteria that is essential for cell division. By interfering with FtsZ assembly, the bacteria are unable to maintain, divide and propagate. Dr. Ojima’s team at ICB&DD will work with Sanofi to optimize these novel benzimidazole-based compounds with the objective to identify drug candidates ready for translational drug development. ICB&DD is very excited to work with Sanofi, a world leading pharmaceutical industry, including therapeutics for TB and other infectious diseases. This collaboration demonstrates ICB&DD’s innovative approach to finding solutions to unmet medical needs.
ICB&DD welcomes Dr. Vincent Yang as a member and Steering Committee member. Dr. Yang is the Chairman of the Department of Medicine in the Stony Brook University School of Medicine. Dr. Yang is a nationally recognized physician-scientist specializing in gastrointestinal (GI) cancers. Dr. Yang’s research interests focus on understanding the molecular mechanisms that control proliferation and differentiation of intestinal epithelial cells and how these processes are perturbed in gastrointestinal malignancies. His clinical interest is focused on hereditary colon cancer syndromes and he works closely with national organizations including the Centers for Disease Control and Prevention (CDC) to establish genetic epidemiology of such diseases. Dr. Yang received his Ph.D. Degree in Biochemical Sciences from Princeton University and his Medical Degree from the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Dr. Yang then served as an Intern and Resident in Internal Medicine at Johns Hopkins University School of Medicine, where he also completed a Fellowship in Gastroenterology, after which he joined the Hopkins faculty, rising to become Associate Professor of Medicine and Biological Chemistry. He then moved, 10 years ago, to Emory University, where he rose to Professor and was appointed as head of the Division of Digestive Diseases. Under his tenure, he recruited 30 new faculty members and an equal number of research staff to the division, including six physician-scientists. Grant funding to the division included over 20 NIH and VA grants and 10 ARRA (American Recovery and Reinvestment Act) awards. Dr. Yang significantly enhanced the academic reputation of the Division of Digestive Disease at Emory. He assumed his current position as the Chair of the Department of Medicine, School of Medicine, Stony Brook University in September 2011. Dr. Yang has been elected to the two most prestigious honor societies devoted to clinical investigation in the U.S., the American Society for Clinical Investigation and the Association of American Physicians. A recipient of numerous awards, he was one of the first to receive the Georgia Cancer Coalition Distinguished Cancer Clinician Scientist Award in 2001. Previously, he received a Sandoz Clinician Scientist Award from The Johns Hopkins University School of Medicine, the American Gastroenterology Association/Sandoz Research Scholar Award and Robert Wood Johnson Medical School Distinguished Alumni Award. Dr. Yang will be an outstanding addition to the Cancer Research Program and other ICB&DD activities.
ICB&DD welcomes Dr. Agnieszka Bialkowska as a Project Member. Dr. Bialkowska is a Research Assistant Professor in the Department of Medicine, School of Medicine, Stony Brook University. Dr. Bialkowska’s major research interest is on the mechanisms of the development and progression of colorectal cancer. Her work focuses on transcription factor Krüppel-like Factor 5 (KLF5), which has been shown to be involved in both processes. Additionally, in cooperation with Scripps Research Institute of Molecular Screening Center (SRIMSC), she utilizes the high-throughput screen method to discover and identify small molecular compounds that modulate activity of KLF5 and impact colon cancer cell proliferation. She is currently collaborating in a study to resolve the role of KLF5 in inflammation. She received her Ph.D. (2003) in Biochemistry from the Polish Academy of Sciences. Previous to joining the Department of Medicine at Stony Brook, she completed a postdoctoral fellowship in gene therapy in the Gene Therapy Program at Louisiana State University. She also performed postdoctoral research at Emory University School of Medicine, Division of Digestive Diseases under the mentorship of Dr. Vincent Yang. Dr. Bialkowska will be an excellent addition to the Cancer Research Program and other ICB&DD activities.
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