Department of Pharmacology & Therapeutics
Associate Member, Roswell Park Cancer Institute
Associate Professor, Department of Molecular and Cellular Biophysics and Biochemistry, Roswell Park Graduate Division, and Department of Structural Biology, State University of New York at Buffalo
Senior Research Scientist, Hauptman-Woodward Medical Research Institute

Telephone: (716) 898-8617 Fax: (716) 898-8660
Address: Hauptman-Woodward Institute
700 Ellicott Street
Buffalo, NY 14203
E-mail: debashis.ghosh@roswellpark.org; ghosh@hwi.buffalo.edu

Education
St. Xavier’s College, University of Calcutta, Calcutta, India, BS, 1974, Physics, Chemistry, Mathematics. with Honors in Physics
Indian Institute of Technology, Kharagpur, India, MS, 1976, Physics
Saha Institute of Nuclear Physics, Calcutta, India, MSc, 1977, Biophysics
University of Pittsburgh, Pittsburgh, PA, PhD, 1981, Crystallography
Carnegie-Mellon University, Pittsburgh, PA, Post-Doc, 1983, Materials Science

General Research Interest
Major research interests and activities involve structural biology of estrogen and androgen biosynthesis and metabolism. Methods used are X-ray crystallographic elucidation of three-dimensional structures of proteins, molecular modeling and other biophysical/biochemical techniques. Targets are important human steroidogenic enzymes, such as cytochrome P450 aromatase, steroid sulfatase, types 1 and 3 17beta-hydroxysteroid dehydrogenase and 5alpha-reductases, that are responsible for biosynthesis and activation of steroids. One objective is to design enzyme specific ligands for anti-cancer therapy. Active projects also include structure-function studies of interphotoreceptor retinoid-binding proteins and rational design of peptide mimics of the melanoma-associated antigen.

Key Publications

Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX. Structure of Human Estrogenic 17b-Hydroxysteroid Dehydrogenase at 2.20Å Resolution, Structure, 3, 503-513 (1995). 

Jörnvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D. Short-Chain Dehydrogenases/Reductases (SDR), Biochemistry, 34, 6003-6013 (1995).

Puranen T, Poutanen M, Ghosh D, Vihko P, Vihko R. Characterization of Structural and Functional Properties of Human 17b-Hydroxysteroid Dehydrogenase Type 1 Using Recombinant Enzymes and Site-Directed Mutagenesis, Molecular Endocrinology, 11, 77-86, 1997.

Peltoketo H, Ghosh D, Vihko P. 17b-Hydroxysteroid Dehydrogenase Type 1: Towards Structure and Function-based Drug Design, Current Topics in Steroid Research, 1, 111-117 (1998).  

Sawicki M, Erman M, Puranen T, Vihko P, Ghosh D. Structure of the Ternary Complex of Human 17b-Hydroxysteroid Dehydrogenase Type 1 with Equilin and NADP+, Proc. Natl. Acad. Sci., USA, 96, 840-845 (1999).

Sawicki MW, Ng PC, Burkhart BM, Pletnev VZ, Higashiyama T, Osawa Y, Ghosh D. Structure of an Activity Suppressing Fab Fragment to Cytochrome P450 Aromatase: Insights into the Antibody-Antigen Interactions, Mol. Immunology, 36, 423-432 (1999).

Li N, Erman M, Pangborn W, Duax WL, Park CM, Bruenn J, Ghosh D. Structure of U. maydis Killer Toxin KP6a-subunit: A Multimeric Assembly with a Central Pore, J. Biol. Chem., 274, 20425-20431 (1999).

Miettinen M, Isomaa V, Peltoketo H, Ghosh D, Vihko P. Estrogen Metabolsim as a Regulator of Estrogen Action in the Mammary Gland, J. of Mammary Gland Biology and Neoplasia 5, 259-270 (2000).

Ghosh D, Vihko P. Molecular Mechanisms of Estrogen Recognition and 17-Keto Reduction by Human 17 Beta-Hydroxysteroid Dehydrogenase Type 1, in: Chemico-Biological Interactions, Vol. 130-132, pp. 637-650 (2001).

Vihko P, Isomaa V, Ghosh D. Structure and Function of 17b-Hydroxysteroid Dehydrogenase Type 1 and Type 2, Mol. Cell. Endocrinol. 171, 71-76 (2001).

Ghosh D, Sawicki M, Lala P, Erman M, Pangborn W, Eyzaguirre J, Gutierrez R, Jörnvall H, Thiel D. Multiple Conformations of Catalytic Serine and Histidine in Acetylxylan Esterase at 0.90Å, J. Biol. Chem., 276. 11159-11166 (2001).

Ghosh D, Sawicki M, Pletnev V, Erman M, Ohno S, Nakajin S, Duax WL. Porcine Carbonyl Reductase: Structural Basis for a Functional Monomer in Short-chain Dehydrogenases/Reductases, J. Biol.Chem., 276, 18457-18463 (2001).

Hernandez-Guzman FG, Higashiyama T, Osawa Y, Ghosh D. Purification, Characterization and Crystallization of Human Placental Estrone/DHEA Sulfatase, A Membrane-bound Enzyme of the Endoplasmic Reticulum, J. Steroid Biochem. Mol. Biol. 78, 441-450 (2001).

Ghosh D, Hernandez-Guzman FG, Higashiyama T, Pangborn W, Osawa Y. Structural consequences of transmambrane association and mechanism of molecular recognition at the active site of human Estrone Sulfatase, a potential target for hormonal breast cancer therapy. European Journal of Cancer 38, S135 (2002).

Hernandez-Guzman FG, Higashiyama T, Pangborn W, Osawa Y, Ghosh D. Structure of Human Estrone Sulfatase Suggests Functional roles of Membrane Association, J. Biol. Chem. 278, 22989-22997 (2003).  

Lala P, Higashiyama T, Erman M, Griswold J, Wagner T, Osawa Y, Ghosh D. Suppression of human cytochrome P450 aromatase activity by monoclonal and recombinant antibody fragments and identification of their stable antigenic complex. J. Steroid Biochem. Mol. Biol. 88, 235-245 (2004).

Sugiyama T, Ohno S, Ghosh D, Nakajin S. 3a/b,20b-Hydroxysteroid Dehydrogenase also has a cysteine residue that is involved in binding of cofactor NADPH. J. Steroid Biochem. Mol. Biol. 88, 393-398 (2004).  

Ghosh D. Mutations in X-linked ichthyosis disrupt the active site structure of Estrone/DHEA Sulfatase. Biochim. Biophys. Acta: Molecular Basis of Disease. 1739, 1-4 (2004).

Lakhman SS, Ghosh D, Blanco JG. Functional Significance of a Natural Allelic Variant of Human Carbonyl Reductase 3. Drug Metabolism and Disposition 33: 254-257 (2005).

Ghosh D. Three-dimensional structures of sulfatases. Methods in Enzymology (invited) (in press).