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Research

OVERVIEW

The Laboratory for Chemical Biology was established in 1988, assisted by a generous gift from Mr. and Mrs. Leo Zickler of Washington, D.C., The Laboratory is directed by Dr. Arthur. P. Grollman M.D., Distinguished Professor of Pharmacological Sciences, Professor of Medicine and Evelyn Glick Professor of Experimental Medicine. The first Director of the laboratory was Dr. Edward Reich, Distinguished Professor of Pharmacological Sciences.

In the LCB, molecular biologists and chemists collaborate on research designed to explore the relationships between structure of damaged DNA and functions of enzymes involved in DNA replication and repair. Towards that end, mechanisms of DNA damage recognition, mutational specificity and DNA repair are studied at the cellular, molecular and atomic levels.

LCB investigators pioneered the development of site-specific systems used to study mechanisms of mutagenesis induced by defined DNA lesions and to elucidate pathways for repair of oxidative DNA damage in mammalian cells. Earlier research from this Laboratory was instrumental in establishing the chemical mechanism by which the radiomimetic anti-tumor drug bleomycin creates double strand breaks in DNA. The powerful and versatile tools of functional genomics and proteomics currently are being brought to bear on this problem.

Translational research by LCB investigators has linked exposure to the antiestrogen tamoxifen with endometrial cancer. Recently, they showed aristolochic acid to be the nephrotoxic and carcinogenic agent responsible for endemic (Balkan) nephropathy and associated urothelial cancer. By so doing, they develop paradigms by which the tools of chemistry, molecular epidemiology and molecular/cellular biology are used to identify causative agents of human disease.


RESEARCH PROJECTS