Ramsden Lab
Principal Investigator: Dale A Ramsden
Institution: University of North Carolina at Chapel Hill (Chapel Hill, NC)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Accepting PhD Students ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY: OVERALL DNA Polymerase theta (Pol θ) in mammalian cells confers resistance to chemotherapeutic drugs like topoisomerase inhibitors and crosslinking agents. It is excessively engaged in cells deficient in a wide variety of other DNA damage response (DDR) genes, including those associated with hereditary breast cancer (BRCA1/2). Thus, while Pol θ inhibition or deficiency is generally tolerated in normal cells, it is lethal in BRCA-deficient cancers (synthetic lethality). Accordingly, inhibitors of Pol θ have been employed in clinical trials as therapy for patients with BRCA-deficient breast or ovarian cancer. We propose here to clarify the mechanism of Pol θ mediated repair and identify cellular contexts most likely to emphasize cancer-specific vulnerability to Pol θ inhibitors Our multidisciplinary program is founded on an interest in molecular mechanism, and address how molecular structure dictates its function using in vitro models. In the context of cellular repair we will address how it functions in its conventional role in repair of chromosomal double strand breaks caused by exogenous agents, like ionizing radiation. We will compare this mechanism to Pol θ func…
Active NIH Awards
- 5P01CA247773-07: Polymerase theta, genome instability, and cancer (2026)
- 5R01CA097096-23: DNA Polymerases in Nonhomologous End Joining (2026)
- 5P01CA247773-07: Core A: Administrative Core (2026)
- 5P01CA247773-07: Project 1: Cellular requirements for Pol theta (2026)
- 2P01CA247773-06: Project 1: Cellular requirements for Pol theta (2025)
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