I am a Professor of Neurosurgery, Biochemistry & Structural Biology. My laboratory research is focused on the responses of mammalian cells to DNA double-strand breaks (DSBs), collectively called the DNA damage response (DDR). We are involved in studying DDR events triggered by ionizing radiation and their carcinogenic and cancer therapeutic implications. We are particularly interested in 1) understanding DSB signaling and repair mechanisms with a focus on the regulation of DNA end resection, 2) the genetic basis of radioresistance and recurrence of glioblastoma (GBM), with the translational objective of targeting DNA repair pathways for GBM therapy, and 3) genetic changes underlying glioma genesis triggered by ionizing radiation, the only known risk factor for the development of GBM. A more mechanistic understanding of DDR events has emerged from our studies, providing important insights into how GBM is triggered and leading to the development of better therapeutic approaches for GBM. Our research has been supported by extra-mural funding from the NIH, NASA, DOD, and CPRIT. To date, I have published over 90 research articles in peer-reviewed journals. In addition, I have played a leading role in course direction, teaching, and mentoring undergraduate, graduate, and medical students at the University of Texas. I have also been involved in mentoring junior faculty by serving on their career development committees. I serve on the editorial boards of several journals and routinely review grants for various NIH, DOD, and NASA study sections. Our laboratory has a long-standing interest in mechanisms underlying repair pathway choice, especially the blockade to EXO1 and other nucleases posed by 53BP1 and associated proteins. Our expertise lies in the use of cell biological approaches to these problems. We have a long-standing collaboration with Dr. Patrick Sung (PI of the Program Project and Senior Investigator of Project 2), whose laboratory uses biochemical approaches to investigate DNA end resection and homology-directed DNA repair. Our collaboration was recently cemented by our move to UT Health San Antonio from UT Southwestern Medical Center and Yale University, respectively. Our two laboratories, with complementary cell biological and biochemical expertise, work together seamlessly on multiple projects including the restriction of DNA end resection, the focus of the proposed project. My laboratory has effectively bridged basic research on DNA repair and translational research on cancer therapy, and I will draw upon this expertise and our synergy with the Sung laboratory for the successful completion of the proposed project. Extensive collaborations with the laboratories of Weixing Zhao, Alexander Mazin, Robert Hromas, Dipanjan Chowdhury, and Eric Greene, who are all senior investigators in our Program Project, further enhance the productivity and impact of our undertakings.