AGEP-T FRAME Fellow: Alejandra Castano
Graduate Student, Stony Brook University
Department of Chemistry
AGEP-T FRAME Research Mentor: Dr. Orlando Scharer
Alejandra Castano graduated Cum Laude with a bachelors degree in chemistry from Queens Collage-CUNY in 2009. During her stay in Queens College she had the opportunity to work under the direction of Dr. Robert Engel from the Chemistry Department synthesizing various polycationic glycosides, carbohydrate gels, polyammonium salts, and ionic liquids for antimicrobial activity. Simultaneously, she also worked on a joined project at Brookhaven National Lab that focused on the synthesis, characterization and radiolytic properties of bis(oxalato)borate containing ionic liquids. These two projects allowed her to co-author four peer-reviewed papers, and launch her career as a scientist. During her undergraduate studies, she was awarded with the NIH MARC U-Star Scholarship. In the fall of 2009, she started a MA degree in the Graduate Center of CUNY, and was awarded the LSAMP- Bridges to the Doctorate Fellowship for two years. However later in the spring of 2010, she decided to switch to the PhD program in chemistry and was subsequently accepted by Stony Brook University for the fall semester of 2010. Since then, she has worked in Dr. Orlando Scharer's lab studying different aspects of DNA repair. She is focused on developing antibodies serving as biomarkers for detection of different cisplatin-DNA adducts. In addition, she investigates the structural stability of glycosydic bonds carrying a fluorine atom at C2' of the guanines that are involved in the formation of various synthetic DNA interstrand crosslinks.
Seminar Title: Generation and Characterization of Adduct-Specific Anti-Ciplatin DNA Antibodies.
Description: Cisplatin is a highly successful chemotherapeutic agent used in the treatment against testicular, bladder, ovarian, cervical, and non-small cell lung cancer. When cellular DNA reacts with cisplatin formation of 1,2-intrastrand crosslink, 1,2-interstrand and 1,3-intrastrand crosslinks occurs. Although treatment with cisplatin has shown high cure rates of testicular cancer (>90% in combination with etoposide ± bleomycin) resistance of tumors to cisplatin remains a significant problem. This resistance occurs through a number of mechanisms, including cellular efflux, inactivation by intracellular thiols and DNA repair and tolerance mechanisms such as the nucleotide excision repair (NER) and the interstrand crosslink (ICL) repair. In light of providing specific information as to how the various adducts contribute to resistance, our group is developing assays to monitor the repair of cisplatin-DNA adducts in cells. For this purpose we are currently generating monoclonal antibodies using synthetic oligonucleotides containing site-specific cisplatin oligonucleotides as immunogens. This approach will allow us to monitor the levels of the different types of cisplatin adducts in tumor cells and tissues and provide insights into how DNA repair and other pathways contribute to resistance.