Robert Eoff, Ph.D.
DNA replication is a complex and perilous undertaking for the cell because the risk of incurring insults to the genome is greatest when the double-helix is unwound for copying. My research team studies what happens when DNA damage is not repaired in a timely manner and ends up blocking the replication machinery. In other words, we study how cells “tolerate” damage for a time in order for the genome to be copied faithfully. These events shape evolutionary processes, influence the emergence of antibiotic resistance in bacteria, promote treatment resistance in cancer patients, and mutations in DNA damage tolerance-related genes underlie a wide range of human diseases.
A long-term goal of my research program is to uncover new mechanistic features of replication stress and DNA damage tolerance by studying these processes at the atomic, molecular and cellular level using a variety of techniques, including biochemical and biophysical approaches, methods related to cellular and molecular biology, and systems level approaches. We also seek to deepen our understanding of how DNA damage tolerance impacts genome stability, patient response to treatment and tumor recurrence in certain cancers.
The major ongoing projects in my lab can be divided into two areas: (1) studying the molecular mechanisms of proteins and enzymes that promote bypass of endogenous barriers to replication, such as G-quadruplexes, and (2) investigating the relationship between DNA polymerase kappa and replication stress, especially as it pertains to cancer stem cells. Additionally, by partnering with Peter Crooks, M.Sc., Ph.D., D.Sc., (Pharmaceutical Sciences, UAMS) and Analiz Rodriguez, M.D., Ph.D., (Neurosurgery, UAMS), we are working to develop small-molecules targeting key elements of the aberrant replication stress response in gliomas and other types of cancer so that we might potentiate the therapeutic effects of treatments like temozolomide and radiation that function by inducing DNA damage.
Biochemistry and Molecular Biology Track
Dr. Eoff and his student, Megan Reed, discussing their research and the graduate program at UAMS.