Agata Smogorzewska, MD, PhD
Year elected: 2016
Current membership category: Active
Rockefeller University
1230 York Avenue
New York, NY 10065
United States of America
Phone: 212-327-7850

Biographical statement

The focus of our research is to understand the mechanism of DNA interstrand crosslink (ICL) repair with the overall goal to gain insights into the cellular and organismal consequences of deficiencies in this type of repair.  ICL repair takes place at sites where the two strands of the DNA have become covalently linked by the byproducts of metabolism or chemotherapeutics preventing replication and transcription.  The repair is accomplished in a multi-step process mediated by the Fanconi anemia pathway and factors that promote Homologous Recombination, including BRCA1 and BRCA2.  Failure of ICL repair results in developmental abnormalities, bone marrow failure, cancer predisposition or kidney failure as seen in Fanconi anemia and karyomegalic interstitial nephritis, two genetic diseases we study. The lab has identified UBE2T, RAD51, and SLX4 as new Fanconi anemia (FANC) genes. Our studies uncovered the key functions of these proteins in activating the DNA repair of ICLs, regulation of DNA processing by appropriate nucleases, and protection of the DNA from the rogue nucleases.  Besides identification and study of new proteins involved in ICL repair, critical questions that we are addressing include why the ICL repair is particularly important in the stem cells, what endogenous metabolites induce ICLs, why and how deficiency of the ICL repair leads specifically to the head and neck cancers, and what is the mechanism of kidney failure when ICL repair is deficient.

Institutional affiliations

The Rockefeller University (Primary)