Professor, Department of Biochemistry and Molecular Pharmacology
One of our major research goals is to elucidate the molecular pathogenesis of the Fanconi Anemia DNA repair and cancer susceptibility pathway and how it interfaces with environmental factors. Over the last decade, research groups, including our lab, have carefully defined and pinpointed the critical genes that are mutated in patients with the Fanconi Anemia (FA) disease. However, it is still unclear how FA proteins and protein complexes in this pathway can work together to alleviate defects in patient cells, such as hypersensitivity to DNA crosslinking agents, replication stress, increased apoptosis, genomic instability, and cellular transformation. My long-standing track record of publications and expertise in the field of Fanconi Anemia, ubiquitin signaling and DNA repair have positioned me with a unique advantage to tackle some of these extraordinary biological problems related to genome integrity and human disease. In the past, we have successfully identified and characterized new FA and FA-related genes whose gene products are activated by ubiquitination and deubiquitination. DNA repair and replication stress response pathways, such as the FA pathway, are critical in preventing chromosomal instability and tumorigenesis. Concerted research efforts from our research group will strive to elucidate new mechanisms that will lead to deeper understanding of how endogenous and environmental factors can influence the FA disease, with the goal of identifying new targets for therapeutic intervention.
Another major research goal involves understanding how deubiquitinating enzymes (DUBs) are regulated under different environmentally-related and physiological conditions (normal vs cancer cells) to cleave monoubiquitinated and/or polyubiquitinated protein substrates. How DUBs are able to discriminate between different substrates or ubiquitin chain types is an emerging area of study, especially in the design of novel inhibitors for cancer therapy and personalized medicine.
Course Director, Protein Modifications in Cell Signaling
PhD from University of Wisconsin
Dana-Farber Cancer Institute, Alan D'Andrea Lab
Nature communications. 2022 Apr 01; 13(1):1740
EMBO reports. 2021 Nov 29; e53543
Cell reports. 2021 Sep 28; 36(13):109754
Nature protocols. 2021 Feb; 16(2):1193-1218
Nature structural & molecular biology. 2019 Jan; 26(1):67-77
Molecular cell. 2019 May 02; 74(3):466-480.e4