Current Projects

The lab’s current work is centered on understanding the function of FA-BRCA proteins in the cellular response to DNA damage, including DNA interstrand crosslinks (ICLs) and DNA double-strand breaks (DSBs) induced by ionizing radiation. We also seek to define the role of FA-BRCA genes/proteins as tumor suppressors, to understand the impact of variants of FA-BRCA genes/proteins, and to apply this knowledge to improving approaches to cancer therapy.

At present, 22 Fanconi anemia (FA) genes have been identified. Eight of the FA genes form a nuclear core complex which, along with FANCT/UBE2T, is required for the monoubiquitination of FANCD2, which is a key step in the FA-BRCA pathway, and of FANCI. We are particularly interested in the function and regulation of FANCD2 in DNA damage responses. 

Several BRCA (breast cancer susceptibility) genes, including FANCS / BRCA1, FANCD1 / BRCA2, FANCN / PALB2, FANCO / RAD51C, FANCU / XRCC2 and FANCJ / BRIP1, are also FA genes but are not required for FANCD2 monoubiquitination. We seek to elucidate their functional relationships to other FA-BRCA proteins, something that is not well understood at present. Other goals include better understanding the function of these proteins in DNA damage responses by characterizing the protein complexes they form, by testing their recruitment to sites of DNA damage and their regulation via post-translational modifications, and by performing functional assays of DNA repair by homologous recombination (HR).

Given our interests in HR and the repair of DSBs, we have initiated an ongoing collaborative project to optimize site-specific template-based gene editing by modifying Cas9.

Diagram of FA-BRCA pathway.
Click to enlarge.

FANCD2 – Related Projects

We are studying the regulation of FANCD2 monoubiquitination by the ATR checkpoint kinase, FANCD2’s function in chromatin and the role of proteins in alternative lengthening of telomeres without telomerase.

FANCD2 Related Projects

BRCA Proteins – Related Projects

Read more about the work we’re doing on interactions of BRCA proteins, FANCN / PALB2 as a linker of BRCA1 and BRCA2 and the relationship of FANCJ / BRIP1 to other FA proteins. BRCA Proteins Related Projects

CRISPR-Cas9 – Related Projects

Learn more about CRISPR-Cas9 related projects. CRISPR-Cas9 Related Projects