Dr. Francesca Cole
The University of Texas MD Anderson Cancer Center
Department of Molecular Carcinogenesis
The Virginia Harris Cockrell Cancer Research Center
My laboratory is located in Smithville, Texas, at UT Science Park
- DNA repair
- Homologous recombination
- Gene conversion
- Mouse genetics
Compromised DNA repair is a common feature of cancers and contributes to loss of genome integrity and tumorigenesis. A critical mechanism to faithfully repair DNA lesions, especially double-strand breaks, is homologous recombination. While many homologous recombination pathway components have been identified, their in vivo roles, especially within mammalian genomic contexts are poorly understood. Research in my laboratory uses genetic and molecular techniques to determine how homologous recombination pathways collaborate, compete, and compensate for one another. In particular, we use newly developed assay systems that take advantage of meiotic recombination in mouse spermatocytes to comprehensively dissect at high-resolution recombination outcomes. We plan to leverage this approach to (1) define the in vivo molecular characteristics of independent DNA repair pathways (2) discover new components of these pathways (3) provide a means of testing chemotherapeutic agents to specifically perturb individual pathways with a hope to improve cancer therapies.
Current studies in my laboratory focus on the patterns and distribution of recombination in both wild type and mutant mice at specific “hotspots” in the mouse genome using PCR based assays. Further, we are developing methods to analyze recombination genome-wide using the latest deep sequencing technology. These studies will inform us about the basic mechanisms of homologous recombination within an in vivo genomic context, but also about the impact of meiotic recombination upon genome diversity and evolution.
A tutorial with us would provide experience in mouse dissection, flow cytometry, immunofluorescence and cytology, single-cell PCR, and recombination analysis.
Cole F, Kauppi L, Lange J, Roig I, Wang R, Keeney S, Jasin M. 2012. Homeostatic control of recombination is implemented progressively in mouse meiosis. Nature Cell Biology, 14: 424-430.
Lange J, Pan J, Cole F, Thelen MP, Jasin M, Keeney S. 2011. ATM controls meiotic double-strand break formation. Nature, 479: 237-40.
Shakya R, Reid LJ, Reczek CR, Cole F, Egli D, Lin CS, deRooij DG, Hirsch S, Kandasamy R, Hicks JB, Szabolcs M, Jasin M, Baer R, Ludwig T. 2011. BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science, 334: 525-528
Cole F, Keeney S, Jasin M. 2010. Comprehensive, fine-scale dissection of homologous recombination outcomes at a hotspot in mouse meiosis. Molecular Cell 39: 700-710.