Congratulations to Anthonya Cooper who successfully defended her dissertation entitled “Communication between Insulin and Serotonin Signaling Pathways in Placenta”.
Department News
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
Dr. Kendrick to Speak at May 16 Event in Hot Springs Village
April 25, 2019 | LITTLE ROCK – You are invited to learn about the latest advances in cancer research, treatment and prevention at a free event at 11:30 a.m. May 16 in Hot Springs Village featuring a researcher from the University of Arkansas for Medical Sciences (UAMS).
The program will be at Diamante Country Club, 2000 Country Club Drive. Featured speaker will be Samantha Kendrick, Ph.D., assistant professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology. Kendrick’s research focuses on developing new therapies for aggressive forms of non-Hodgkin’s lymphoma that have the potential to reduce drug resistance and lead to better patient outcomes.
There is no charge to attend, and lunch is provided. To make a reservation, email mmgarcia@uams.edu or call (501) 526-6990, Ext. 8157 by May 10.
Kendrick was co-recipient of the UAMS Cancer Institute’s 2019 Seeds of Science grant award, which totaled $50,000 and was funded by proceeds from the Village Walk for Cancer Research. Since 2002, the walk has raised about $500,000 for research programs at the UAMS Cancer Institute. The 2019 walk is scheduled for Sept. 28 at Balboa Pavilion in Hot Springs Village.
This event is presented by the UAMS Winthrop P. Rockefeller Cancer Institute in conjunction with the Hot Springs Village Walk for Cancer Research. It is sponsored by the Envoys, an advocacy group of the Winthrop P. Rockefeller Cancer Institute Foundation.
On the Cover
Congratulations to first author, Kirk West, and other members of Alan Tackett‘s lab on their manuscript, Proteomic characterization of the arsenic response locus in S. cerevisiae, that is featured on the cover of Epigenetics.
Congratulations Dr. Delgado!
Congratulations to Magdalena Delgado who successfully defended her dissertation entitled “Characterization of cell death induced by microtubule targeting agents in primary acute lymphoblastic leukemia cells” on April 24th. Magdalena is a student in Timothy Chamber’s lab.
On the Cover
Congratulations to first author, Jun Gao, and other members of Kevin Raney‘s lab on their manuscript, DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA, that is featured on the cover of Chemical Communications.
March Publications
Generation of a Fully Human scFv that binds Tumor-Specific Glycoforms.
Lu Z, Kamat K, Johnson BP, Yin CC, Scholler N, Abbott KL.
Sci Rep. 2019
Gao J, Byrd AK, Zybailov BL, Marecki JC, Guderyon MJ, Edwards AD, Chib S, West KL, Waldrip ZJ, Mackintosh SG, Gao Z, Putnam AA, Jankowsky E, Raney KD.
Chem Commun (Camb). 2019
Local and Relayed Effects of Deep Brain Stimulation of the Pedunculopontine Nucleus.
Garcia-Rill E, Tackett AJ, Byrum SD, Lan RS, Mackintosh SG, Hyde JR, Bisagno V, Urbano FJ.
Brain Sci. 2019
Chronic Kidney Disease and the Gut Microbiome.
Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM.
Am J Physiol Renal Physiol. 2019
Students in Miller Lab Attend Meeting in Baltimore
Allie Davis and Dustyn Barnette, graduate students in Dr. Grover Paul Miller’s lab attended the Society of Toxicology National Meeting in Baltimore, MD last weekend and presented their research. Allie presented a poster entitled ” Bioactivation of Halogenated Aromatic Drugs as Precursors to Drug-Induced Hepatotoxicity” and Dusty presented a poster entitled “Determining Mechanism of Thiazole Metabolically Activated Toxic Outcome through Experimental and Computational Techniques”.
Cancer Institute Member Spotlight
March 14, 2019
Isabelle Racine Miousse, Ph.D.
Assistant Professor
Department of Biochemistry and Molecular Biology
UAMS College of Medicine
Research Interest Statement
Cancer cells fundamentally differ from healthy cells in the way they metabolize the amino acid and methyl donor methionine. This phenomenon is known as methionine dependence. It manifests as an increased reliance on an exogenous supply of methionine for growth and alterations in DNA and histone methylation patterns.
My work investigates these crucial differences between healthy cells and cancer cells. My expertise covers the absorption, processing and utilization of methyl groups, as well as epigenetic changes associated with cancer. I utilize metastatic melanoma models in vitroand in vivo to investigate the molecular bases of methionine dependence, relate dietary methionine levels to changes in the gut environment, and, finally, leverage this knowledge to improve the response rate in patients with metastatic melanoma receiving immunotherapy. With my work, I aim to improve the outcomes of cancer therapy for patients.
Dr. Miousse’s Grants
Pilot Award, UAMS College of Medicine
$25,000*
01/01/19 – 12/31/19
Methionine and autophagy in metastatic melanoma
*cancer-related annual direct costs
UAMS Collaborators
Alan Tackett, Ph.D. (Biochemistry and Molecular Biology)
Igor Koturbash, M.D., Ph.D. (Environmental and Occupational Health)
Stephanie Byrum, Ph.D. (Director of Bioinformatics Core, Arkansas Children’s Research Institute)
Stepan Melnyk, M.D., Ph.D. (Director of the Core Metabolomics Laboratory, Arkansas Children’s Research Institute)
Laxmi Yeruva, Ph.D. (Pediatrics)
Alicia Byrd, Ph.D. (Biochemistry and Molecular Biology)
External Collaborators
David Rosenblatt, M.D., Ph.D. (McGill University)
Alexandra Noel, Ph.D. (LSU School of Veterinary Medicine)
Opportunities for Collaboration
I welcome collaborations on the topics of DNA and histone modifications, as well as methyl donors such as folic acid and vitamin B12. I also have an interest in nutrition and metabolism.
You Might Not Know That …
I have two passions outside of work. I enjoy cooking, for the creative aspect (anything but desserts!) I also enjoy rock climbing for the problem-solving skills it requires and have done that for 10 years.
Cancer-related Publications
Miousse IR, Ewing LE, Kutanzi KR, Griffin RJ, Koturbash I. DNA Methylation in Radiation-Induced Carcinogenesis: Experimental Evidence and Clinical Perspectives. Crit Rev Oncog. 2018;23(1-2):1-11.
Miousse IR, Tobacyk J, Quick CM, Jamshidi-Parsian A, Skinner CM, Kore R, Melnyk SB, Kutanzi KR, Xia F, Griffin RJ, Koturbash I. Modulation of dietary methionine intake elicits potent, yet distinct, anticancer effects on primary versus metastatic tumors. Carcinogenesis. 2018 Sep 21;39(9):1117-1126.
Miousse IR, Pathak R, Garg S, Skinner CM, Melnyk S, Pavliv O, Hendrickson H, Landes RD, Lumen A, Tackett AJ, Deutz NEP, Hauer-Jensen M, Koturbash I. Short-term dietary methionine supplementation affects one-carbon metabolism and DNA methylation in the mouse gut and leads to altered microbiome profiles, barrier function, gene expression and histomorphology. Genes Nutr. 2017 Sep 6;12:22.
Miousse IR, Chang J, Shao L, Pathak R, Nzabarushimana É, Kutanzi KR, Landes RD, Tackett AJ, Hauer-Jensen M, Zhou D, Koturbash I. Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation. Int J Mol Sci. 2017 Jul 4;18(7). pii: E1430.
Miousse IR, Tobacyk J, Melnyk S, James SJ, Cheema AK, Boerma M, Hauer-Jensen M, Koturbash I. One-carbon metabolism and ionizing radiation: a multifaceted interaction. Biomol Concepts. 2017 May 24;8(2):83-92.
Miousse IR, Kutanzi KR, Koturbash I. Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications. Int J Radiat Biol. 2017 May;93(5):457-469.
Student Research Day 2019
Students and postdocs from across campus participated in the 2019 Student Research Day poster presentations on March 12th. Numerous award winners are affiliated with the Biochemistry and Molecular Biology department. The Bhuvan Award is given to the project which makes the best use of biochemistry. Andrea Edwards (Raney lab), Duah Alkam (Ussery and Smeltzer labs) and Joseph Rom (Smeltzer lab) were the winners. Zach Waldrip (Burdine lab) and Alicja Urbaniak (Chambers lab) earned the top two prizes in the post-doctoral category and Zach also won the best poster overall. Congratulations to all!
Andrea Edwards, 1st place Bhuvan Award
Duah Alkam, 2nd place Bhuvan Award
Joseph Rom, 3rd place Bhuvan Award
Dr. Zach Waldrip, 1st place postdoctoral category and 1st place overall
Dr. Alicja Urbaniak, 2nd place post-doctoral category