Jeremy Stark, Ph.D.
- Associate Professor, Department of Cancer Genetics and Epigenetics
Jeremy Stark, Ph.D.
- Cancer Biology
- Cancer Genetics and Epigenetics
The long-term goal of our laboratory research program is to understand the factors and pathways that influence mammalian genome stability. Such studies provide important insights into the etiology of cancer, as well as the mechanisms of cancer cell resistance to clastogenic therapeutics. In one of our central projects, we are seeking to define the factors that limit chromosomal rearrangements during the double strand break (DSB) repair pathway end joining, and thereby develop therapeutic targets for tumor radiosensitization. To advance this goal, we developed a unique assays to quantify the use of correct versus incorrect ends during end joining (EJ) of multiple DSBs, as well as the mechanism of a mutagenic sub-pathway called Alternative-EJ. Using this approach, we are currently focused on defining the role of the several DNA repair factors these aspects of EJ that is poorly understood, yet is critical to limit genome rearrangements, and is likely important for radioresistance.
Other projects in the lab are focused on characterizing the homologous recombination (HR) DNA repair pathway, particularly a mutagenic sub-pathway called Single Stranded Annealing (SSA). For example, we are seeking to define genes that affect the requirement for the tumor suppressor BRCA1 during HR. Inherited mutations in BRCA1 result in defects in the HR pathway of DNA repair, which likely causes an accumulative loss of genetic information that contributes to increased risk of breast and ovarian cancer. We seek to identify genes that influence the requirement for BRCA1 during HR, and hence affect the probability that loss of BRCA1 will cause an increase in cancer risk. These studies are part of an overall effort do identify the genetic regulation of HR that favors conservative repair that is relatively restorative to the genome, versus HR events that are prone to genetic loss (such as SSA).
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