Research Interests.

My major research interest involves the structural biology of estrogen and androgen biosynthesis and metabolism. The methods we use are the X-ray crystallographic elucidation of three-dimensional structures of proteins as well as other biophysical/biochemical techniques.  Targets are important steroidogenic enzymes such as cytochrome P450 aromatase, estrone sulfatase types 1 and 3, 17b-hydroxysteroid dehydrogenase, and 5a-reductases that are responsible for the biosynthesis and activation of steroids. Estrogens and androgens are responsible for the proliferation of hormone-dependent breast and prostate tumors.  One objective of our research is to design enzyme-specific ligands for anti-cancer therapy. 

In addition, in collaboration with SUNY-Buffalo ophthalmologist Dr. Federico Gonzalez-Fernandez, we are investigating the structure-function relationships of interphotoreceptor retinoid-binding proteins (IRBP) linked to macular degeneration and retinitis pigmentosa.  IRBP molecules are involved in the transportation of vitamin A from Muller cells to the photoreceptors that convert light to neural signals.  Elucidation of the molecular basis of interaction between vitamin A and IRBP will reveal functional roles of IRBP in the vision cycle.

My third project deals with the elucidation of the molecular basis of antigen mimicry by anti-idiotypic antibodies.  In collaboration with immunologist Dr. Soldano Ferrone of Roswell Park Cancer Institute, we are attempting to design rational peptide mimics of the high-molecular weight, melanoma-associated antigen (HMW-MAA) for possible use as vaccines.  The plan is also to use rationally modified recombinant fragments of HMW-MAA that could break self-antigen tolerance by the immune system and elicit antibody response against melanoma cells.