Associate Professor

Robert Eoff

Member Winthrop P. Rockefeller Cancer Institute

Ph.D., University of Arkansas for Medical Sciences
B.S., Henderson State University

E-mailrleoff@uams.edu
Office:  (501)686-8343 – Biomedical Research Center 1 B421E
Lab:  (501)603-1004 – Biomedical Research Center 1 B416
FAX:  (501)686-8169

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.

Selected Publications

Eoff, R.L., McGrath, C.E., Maddukuri, L., Salamanca-Pinzon, G.S., Marquez, V.E., Marnett, L.J., Guengerich, F.P., and Egli, M. (2010) “Selective modulation of DNA polymerase activity by fixed conformation nucleoside analogues” Angew. Chem. Int. Ed. Engl. 49, 7481-7485

Eoff, R.L., Choi, J-Y., and Guengerich, F.P. (2010) “Mechanistic studies with DNA polymerases reveal complex outcomes following bypass of DNA damage” J. Nucleic Acids 2010

Maddukuri, L., Eoff, R.L., Choi, J-Y., Rizzo, C.J., Guengerich, F.P., and Marnett, L.J. (2010) “In vitro bypass of the major malondialdehyde- and basepropenal-derived DNA adduct by human DNA Y-family polymerases kappa, iota, and Rev1” Biochemistry 49, 8415-8424.

Eoff, R.L., and Raney, K.D. (2010) “Kinetic mechanism for DNA unwinding by multiple molecules of Dda helicase aligned on DNA” Biochemistry 49, 4543-4553.

Eoff, R.L., Ponce-Sanchez, R., and Guengerich, F.P. (2009) “Conformational changes during nucleotide selection by Sulfolobus solfataricus DNA polymerase Dpo4” J. Biol. Chem. 284, 21090-21099.

Irimia, A.*, Eoff, R.L.*, Guengerich, F.P., and Egli, M. (2009) “Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase – opposite the 7,8-Dihydro-8-oxo-2′-deoxyguanosine adduct” J. Biol. Chem. 284, 22467-22480