WWAMI Lecture: Dr. Margaret Black on 'A Tale of Two CDs: Improving Cytosine Deaminases for Cancer Gene Therapy' on April 26

Monday, April 26, 1-2 p.m.

Rasmuson Hall, Room 117

Dr. Margaret Black is an associate professor and the J. Roberts and Marcia Fosberg Distinguished Professor in the Department of Pharmaceutical Sciences at Washington State University and is also affiliated with the WSU School of Molecular Biosciences. Dr. Black is a faculty candidate for the Alaska WWAMI associate/full professor of biomedical sciences position and is an Alaska INBRE faculty candidate.

Enzymes involved in nucleic acid biosynthesis are a major focus of Dr. Black's research. Dr. Black's laboratory is primarily interested in the structure to function relationship of enzymes that catalyze the formation of precursors for DNA and RNA and, most notably, also convert nucleoside analogs or prodrugs to cytotoxic compounds. Using several mutagenesis and molecular strategies, her laboratory targets these enzymes and selects for variants with altered activities towards the nontoxic prodrugs.  Biochemical evaluation along with in vitro and in vivo analysis of derived mutants that display enhanced prodrug activation allows the identification of mutants for use in gene therapy for the treatment of cancer.

In a process known as suicide gene therapy, a nucleoside metabolizing gene is delivered to a cancer cell followed by administration of the nontoxic prodrug. The gene product (enzyme) converts the prodrug to a cytotoxin, thereby leading to death of the cancer cell. Structural determination and molecular modeling of the active sites of enzymes and their variants provides further insight to how the enzymes might be altered to improve prodrug activation and therefore enhance tumor ablation for a safer and more effective cancer cure.

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