Dale A Ramsden
University of North Carolina at Chapel Hill, NC·Biochemistry
Cells constantly repair breaks that cut both strands of their DNA. How they do it decides whether the genome stays intact, and it also shapes how well cancer treatments work.
- Fields
Biochemistry
Genetics
Pharmacology
- Topics
DNA repair
DNA polymerase theta
Pol θ
- Grants
- 3 known grants, through Jun 2030
What they work on
- Determine how Pol θ's interactions with the DNA-copying machinery, including the polymerase Pol δ and the DNA clamp PCNA, affect cells' need for Pol θ-mediated end joining.
- Investigate how cellular regulation of Pol θ activity changes cells' dependence on it, focusing on changes relevant to cancer therapy and the DNA damage response.
- Identify the molecular factors that make Pol θ necessary for cells to resist topoisomerase 1 inhibitors, chemotherapy drugs that cause stress during DNA copying.
- Investigate how NHEJ repairs the second strand of a DNA break and replaces the RNA that polymerases add to the first strand when starting repair.
- Test a candidate mechanism for removing the 11–15 nucleotide RNA primer that steers DNA break repair toward NHEJ, a step that preliminary data indicate repair requires.
- Compare how drug inhibition and genetic loss of one or both end-joining pathways affect genome stability, including when NHEJ polymerases cannot add RNA.
More about the research
Radiation and many chemotherapy drugs kill tumor cells by breaking DNA, so the repair pathways cells use can make these treatments more or less effective. This research asks how two break-repair pathways work at the molecular level. The first is DNA polymerase theta (Pol θ), an enzyme that drives a backup repair pathway many cancers depend on. The second is nonhomologous end joining (NHEJ), the main pathway that glues broken DNA ends back together.
Why it matters
Pol θ inhibitors are already in clinical trials for patients with BRCA-deficient breast and ovarian cancer. Identifying which cancers depend most on Pol θ could help match these drugs to the patients most likely to benefit. Understanding how NHEJ repairs radiation damage, and how clinical NHEJ inhibitors act in cells, could help make radiation therapy more effective, including for hereditary breast cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Joseph J. Loparo
Harvard University, MA·Biochemistry
Determine how core and accessory non-homologous end joining factors cooperate to tether broken DNA ends, using single-molecule imaging of the synaptic complex in a physiological cell-free system.
Zhiyuan Shen
Rutgers University-New Brunswick, NJ·Biochemistry
Reveal how chromatin context, shaped by methylation, sumoylation and ubiquitination tags, controls the recruitment and function of the BRCA1-PALB2-BRCA2 repair complex and regulators such as 53BP1, RNF4 and BARD1.
Francesca Storici
Georgia Institute of Technology, GA·Genetics
Build matched human kidney (HEK293T) and diploid retinal pigment epithelial (RPE-1) cell lines expressing spliced or non-spliced RNA from the same AAVS1 safe-harbor insertion site, and measure how each transcript changes end-joining repair of CRISPR/Cas9 breaks using deep sequencing.
The school
University of North Carolina at Chapel Hill: 72 labs on PI Pages, $1.6B a year on research, 523 research doctorates a year.
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