CIE Researcher of Distinction, September 2016
Vincent M. Alford
Each month, the Center for Inclusive Education showcases the outstanding research being conducted by one of our talented scholars in our Research Café series. In addition, we recognize this scholar as a Researcher of Distinction and share the details of his/her journey to becoming an accomplished scholar. This month's Researcher of Distinction is Vincent M. Alford, PhD candidate in the Department of Molecular & Cellular Pharmacology. Vincent presented his talk, ‘Development of Non-Catalytic Small Molecule Inhibitors of Matrix Metalloproteinase 9 in Cancer Therapeutics’ on Monday, September 19, 2016.
Vincent's Path Into Research
I am originally from Florida where I completed my bachelor’s degree in Microbiology and Cell Science at the University of Florida (UF). During my second year at UF, I joined the lab of Dr. Eric Triplett where I worked on a project aimed at understanding how the immune system is in direct correlation with causing juvenile/type II diabetes. In the lab, I dedicated my time and efforts to help discern the control mechanisms, environmental factors, and immunological responses involved in this chronic ailment. Upon attending Stony Brook University’s Molecular and Cellular Pharmacology graduate program, my research interest shifted towards understanding the molecular mechanisms behind cancer dissemination along with developing anti-cancer drugs to prevent both early and late stages of tumor development. Under the guidance of my mentor Dr. Jian Cao, I have been able to strengthen and expand my graduate training through undertaking a project involving the development of a standard approach for rational drug design against the functional activity of individual matrix metalloproteinases (MMPs). I am both a Bridge to the Doctorate (BD) and Chemical Biology Training Program (CBTP) fellow.
Vincent's Current Research
Describe the work you presented for your Research Café.
Metastasis accounts for 90% of all human cancer related deaths yet even with its clinical relevance, we lack adequate drugs to target this biological process often associated with aggressive cancers. Proteases such as matrix metalloproteinases (MMPs) were found to not only be highly associated with but also, required in this active process whereby they degrade surrounding connective tissue between cells along with the linings of blood vessels allowing tumor cells to escape their primary location and seed secondary tumors elsewhere. Overexpression of MMPs, especially MMP-9, is often associated with poor prognosis in patients, which is attributed to this enzyme’s known role in establishing a highly enriched tumor microenvironment through cleavage of extracellular matrix proteins resulting in an accumulation of growth factors necessary for supporting the demands of a rapidly proliferating malignancy. Although MMPs represent the most prominent family of proteinases associated with tumorigenesis, drugs designed to inhibit their proteolytic activities largely failed in pre-clinical trials due to issues with selectivity for individual MMPs. Due to how highly conserved the catalytic domain is within this family of zymogens, a paradigm shift in the development of novel MMP inhibitors (MMPI) targeting less conserved, non-catalytic functional domain(s) of the proteases to increase target specificity and selectivity was adopted. To advance our understanding of the non-catalytic functional domain(s) of these proteases, our lab has previously demonstrated for the first time that secreted proMMP-9 is sufficient to induce cancer cell migration independent of proteolytic activity through the formation of a homodimer. To this end, our lab has identified inhibitors, which effectively reduce MMP9-mediated cancer cell migration in addition to reducing their metastatic potential in in vivo mouse xenograft models. To increase the potency of the identified MMP-9 inhibitor, we have designed and synthesized 15 derivates in collaboration with Dr. Iwao Ojima (Director of Institute of Chemical Biology & Drug Discovery, Stony Brook University, NY)based on the parental compound. My contribution to this research project has led to the identification of a more potent and selective MMP-9 inhibitor through characterization of these 15 derivative compounds, which not only display promising inhibitory potential in in vitro cell based migration assays but also, shows promising preliminary results in reducing cancer cell invasive and angiogenic promoting potential.
Are there any other projects, beyond your Research Café work, that you are currently working on?
Identify and design therapies against key signaling pathways involved in cancer stem cell (CSC) maintenance and chemoresistance. After identification and characterization of these druggable targets, our hopes are to use small molecules to resensitize CSCs to conventional chemotherapeutic agents thereby preventing tumor relapse.
What was the deciding factor for you to come to Stony Brook for your graduate studies?
I made my decision to attend SBU because of my department. The Molecular & Cellular Pharmacology department were very nurturing in helping me prepare for a career in academia. In addition to this, the research performed by the department appealed to me due to it’s relevance with medical/human health driven concerns.
What are your future goals?
After finishing my doctorate here at Stony Brook, my goal is to then pursue an academic post-doctoral position in which I can continue my research in studying and developing inhibitors, which target cancer dissemination. My long-term career goal would be to combine my teaching, pharmacological and chemical biology training to establish my own lab dedicated to furthering the education of students interested in pursuing research careers in the field of cancer dissemination and drug discovery.
What do you enjoy most about research?
I enjoy how each day there is something new to perform and discover in lab. There is never a dull moment in research since you never know what you will discover next and what impact that might have on changing the way the scientific community views/interprets that particular area of ongoing work.