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April 25, 2019

Cancer Institute Member Spotlight

April 25, 2019

Robert Eoff, Ph.D.

Associate Professor
Department of Biochemistry & Molecular Biology
College of Medicine
Biochemistry Track Leader for the Graduate Program in Interdisciplinary Biomedical Sciences

Research Interest Statement

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, such as proteomics. 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.

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 standard-of-care drugs like Temodar.

Dr. Eoff’s Grants

National Cancer Institute
Translesion DNA polymerase kappa activity in gliomas
04/04/2014 – 02/28/2020*
$207,500*

UAMS Foundation/Medical Research Endowment
DNA polymerase kappa inhibitors
01/01/2019 – 12/31/2019
$15,000*

UAMS Seeds of Science
DNA polymerase kappa inhibitors
02/01/2019 – 1/31/2020
$15,000*

UAMS Arkansas Breast Cancer Research Program
Investigating Mechanisms of Treatment Resistance in Breast Cancer Stem Cells
02/01/2019 – 1/31/2020
$248,699*

UAMS COM Barton Bridging Grant
DNA polymerase kappa regulation and activity in gliomas
01/01/2019 – 1/01/2020
$45,000*
*cancer-related annual direct costs

Dr. Eoff’s UAMS Collaborators

Analiz Rodriguez, M.D., Ph.D.

Justin Leung, Ph.D.

Kevin Raney, Ph.D.

Alan Tackett, Ph.D.

Peter Crooks, M.Sc., Ph.D., D.Sc.

Michael Borrelli, Ph.D.

Grover P. Miller, Ph.D.

Dr. Eoff’s External Collaborators

Michelle Hamm, Ph.D. (University of Richmond)

Julie Gunderson, Ph.D. (Hendrix College)

Shana Sturla, Ph.D. (ETH, Zürich, Switzerland)

Jeong-Yun Choi, M.D., Ph.D. (Sungkyunkwan University School of Medicine, South Korea)

 

Opportunities for Collaboration

My group has expertise in structural enzymology and molecular biology. While we are primarily interested in genomic maintenance, I’m curious about many scientific areas and welcome conversations about collaborating on a wide range of topics.

You Might Not Know That …

I’ve been a volunteer youth soccer coach for over a decade. I enjoy mixed martial arts training, and I like to combine my love of science with my passion for illustration. Also, one of my favorite ways to relax is by spending time with my family in the great outdoors.

Cancer-related Publications

LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. West KL, Kelliher JL, Xu Z, An L, Reed MR, Eoff RL, Wang J, Huen MSY, Leung JWC. Nucleic Acids Res. 2019 Apr 15. pii: gkz263. doi: 10.1093/nar/gkz263. [Epub ahead of print] PMID:30982887

A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells. Zafar MK, Maddukuri L, Ketkar A, Penthala NR, Reed MR, Eddy S, Crooks PA, Eoff RL. Biochemistry. 2018 Feb 20;57(7):1262-1273. doi: 10.1021/acs.biochem.7b01176. Epub 2018 Jan 30. PMID:29345908

Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities. Zafar MK, Eoff RL. Chem Res Toxicol. 2017 Nov 20;30(11):1942-1955. doi: 10.1021/acs.chemrestox.7b00157. Epub 2017 Sep 28. Review. PMID:28841374

Synthesis and Evaluation of 2-Naphthaleno trans-Stilbenes and Cyanostilbenes as Anticancer Agents. Madadi NR, Penthala NR, Ketkar A, Eoff RL, Trujullo-Alonso V, Guzman ML, Crooks PA. Anticancer Agents Med Chem. 2018;18(4):556-564. doi: 10.2174/1871521409666170412115703. PMID:28403783.

Kynurenine signaling increases DNA polymerase kappa expression and promotes genomic instability in glioblastoma cells. Bostian, AC, Maddukuri L, Reed MR, Savenka T, Hartman JH, Davis L, Pouncey DL, Miller GP, Eoff RL. Chem Res. Toxicol. 2016 Jan 19;29(1):101-8. doi: 10.1021/acs.chemrestox.5b00452. PMID: 26651356