(PhD – University of Toronto)
HONORS & AWARDS
- Leukemia and Lymphoma Society Scholarship: 2006-2011
- Jefferson Pilot Fellowship: 2003-2006
- Searle Scholar: 1999-2002
- Cancer Research Institute Fellowship: 1996-1998
- Governor General’s Gold Medal: 1994
Ramsden lab were the first to link several newly described DNA polymerases to NHEJ, and then showed how three different DNA polymerases make unique contributions to this pathway. They have varying substrate requirements that dictated their biological roles, and additionally have varying affinity for the NHEJ holoenzyme, ensuring a hierarchy of recruitment. His lab has additionally collaborated with several other groups in the research triangle area (Drs Kunkel, Pederson, and London, NIEHS; Dr. Lee, UNC) to clarify the structural basis for these differing biochemical characteristics.
Ramsden lab determined another component of NHEJ, Ku, has several unanticipated functions. His lab first determined it is sufficient for a kind of ?passive? chromatin remodeling: it peels DNA off the surface of nucleosomes without the typical requirement for ATP hydrolysis. More recently we characterized Ku as an enzyme. It is an AP lyase, and helps process damaged ends expected in the course of chromosome break repair. It is surprisingly one of the primary sources of AP lyase activity in cell extracts, and is uniquely active on its expected biological substrate (double strand breaks).
Mammals use three distinct pathways for repairing chromosome breaks. Ramsden lab is interested in the mechanistic details of how each pathway works, but also how and why a given pathway is chosen, and the consequences of choosing the “wrong” pathway. Ramsden lab’s work has relevance to normal organismal development and aging, as well as carcinogenesis and cancer therapy. Notably, repair of chromosome breaks is also central to genome engineering.
Ramsden lab uses diverse approaches, including biochemical analyses and somatic cell genetics. Ramsden lab also work closely with a wide variety of labs with expertise in protein structure determination, biophysics, cell biology, and model organism genetics.