Mammalian Replication Stress Response:

DNA replication stress is a complex phenomenon that is often defined by the slowing or stalling of replication fork progression and/or DNA synthesis. Failure to properly resolve replication stress in a timely manner can contribute towards genome instability, cell cycle defects and human disease; however, it remains poorly understood how this process is controlled by multiple pathways in cells. Our lab studies how the Fanconi Anemia (FA) cancer susceptibility pathway regulates replication stress response through the control of replication fork dynamics. We use cutting-edge tools, including single-molecule DNA fiber analysis and mass spectrometry-based proteomics, to understand how post-translational modifications regulate different components of the FA pathway and the replisome.

 

Neuronal DNA Damage Signaling:

Post-mitotic neuronal cells have a unique take on the DNA damage response (DDR). While most non-neuronal dividing cells attempt to subvert DNA damage through extensive DNA repair and checkpoint signaling, neuronal cells welcome intrinsic DNA damage as a means to control cell growth and transcriptional activation. How different DNA repair pathways are re-wired in neuronal cells to control growth and gene expression is not well-understood. We use a primary neuronal cell culture system to interrogate this question and others.

 

Deubiquitinases (DUBs) in Cancer:

Ubiquitination is a highly regulated process conserved in all eukaryotes that controls a broad range of cellular functions, from proteolysis, signal transduction, endocytosis, to DNA repair and genomic stability. Like phosphorylation, ubiquitination can be a dynamic and reversible post-translational process whereby an enzyme cascade conjugates ubiquitin to a target protein, and a family of proteases, the deubiquitinases (DUBs), are potent at removing this modification. In humans, protein deubiquitination is controlled by a family of over 90 distinct DUB enzymes, of which the majority has not been functionally characterized. We are currently interested in understanding how DUB activity in cells are controlled in a specific manner and to identify novel substrates for DUBs that are important in the regulation of cell growth control and genome stability pathways.