Dr. Zhiqiang Qin, Associate Professor of Pathology, and Dr. Lu Dai, Assistant Professor of Pathology, recently published a paper in PLOS Pathogens that discusses the development of new HDACs/BRD4 dual inhibitors targeting virus-associated lymphomas. Research staff members Dr. Jungang Chen and Dr. Zhengyu Wang made major contributions to both studies. Additional UAMS collaborators included the Dr. Hong-Yu Li, a Professor of Pharmaceutical Sciences in the College of Pharmacy, Dr. Steven Post, Professor of Pathology, and Dr. Samantha Kendrick, Assistant Professor of Biochemistry and Molecular Biology.

Polλ promotes microhomology-mediated end-joining.
Chandramouly G, Jamsen J, Borisonnik N, Tyagi M, Calbert ML, Tredinnick T, Ozdemir AY, Kent T, Demidova EV, Arora S, Wilson SH, Pomerantz RT.
Nat Struct Mol Biol.

Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation.
Meagher M, Myasnikov A, Enemark EJ.
Int J Mol Sci.

Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model.
Garg TK, Garg S, Miousse IR, Wise SY, Carpenter AD, Fatanmi OO, van Rhee F, Singh VK, Hauer-Jensen M.
Int J Mol Sci.

By Marty Trieschmann

LITTLE ROCK — Samantha Kendrick, Ph.D., Assistant Professor in the Department of Biochemistry and Molecular Biology at the University of Arkansas for Medical Sciences (UAMS), has received a $760,000 grant from the U.S. Department of Defense to study a fast-growing type of non-Hodgkin lymphoma common among veterans and military personnel.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive blood cancer that affects B-lymphocytes, a type of white blood cell that makes antibodies to fight infections and are an important part of the lymphatic system. Second only to melanoma, DLBCL is the fastest growing cancer in the world and accounts for 30% of cancer cases worldwide. More than 18,000 people are diagnosed with DLBCL each year.

Funded by the Defense Department’s Congressionally Directed Medical Research Program, Kendrick’s three-year study entitled, “Targeting Unique DNA Structures to Repress Oncogenic Signaling in Lymphoma,” will use sophisticated technology called proteomics to identify proteins that interact with a unique DNA structure called the G-quadruplex (G4) that forms within a regulatory region of a key B-cell receptor gene.

“This grant will allow us to understand the underlying biology of one of the most common B-cell cancers and what is really driving some of the aggressive tumors that are unresponsive to current therapy,” added Kendrick, a cancer researcher at the UAMS Winthrop P. Rockefeller Cancer Institute whose husband is a veteran and lymphoma survivor.

Lymphoma is among one of many cancers that can be connected to a veteran’s military service. Nearly 13,000 veterans with non-Hodgkin’s lymphoma received VA disability compensation in 2021. Lymphoma is often linked to exposure to toxic substances, which is the case for many military service members. Risk for lymphoma is 50% higher for Vietnam veterans.

“Lymphomas are not single diseases but consist of multiple subsets that will require personalized medicine for some patients to survive,” said Kendrick. “It’s very exciting to be part of this foundational research to better understand how these tumors develop.”

“Dr. Kendrick is one of our rising research stars in the UAMS Winthrop P. Rockefeller Cancer Institute,” said Alan Tackett, Ph.D., deputy director of the Cancer Institute. “Her research will shed light on the underlying principles of DLBCL biology that will enable the development of the next generation of therapies to treat this aggressive disease.”

Kendrick has been studying lymphoma for more than a decade, beginning as a doctoral student at the University of Arizona. Originally from Canada, she completed her undergraduate and graduate studies at McMaster University in Ontario.  She is the recipient of a 2013 Lymphoma Research Foundation Postdoctoral Fellowship and is a Leukemia and Lymphoma Society Woman of the Year nominee. She joined UAMS in 2017.

On December 5, 2022, Binyam Belachew successfully defended his dissertation entitled “Biophysical and biochemical methods to determine the ability of hepatitis C virus non-structural protein 3 to unfold viral G-quadruplex RNA structures.” Dr. Belachew was mentored by Dr. Kevin Raney. He has accepted a position as a Specialist for the Biology Instructional Office at the University of Texas at Austin.

Two Distinct Modes of DNA Binding by an MCM Helicase Enable DNA Translocation.
Meagher M, Myasnikov A, Enemark EJ.
Int. J. Mol. Sci.

De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.
Vinson DA, Stephens KE, O’Meally RN, Bhat S, Dancy BCR, Cole RN, Yegnasubramanian S, Taverna SD.
Epigenetics Chromatin.

Enteroviral 2C protein is an RNA-stimulated ATPase and uses a two-step mechanism for binding to RNA and ATP.
Yeager C, Carter G, Gohara DW, Yennawar NH, Enemark EJ, Arnold JJ, Cameron CE.
Nucleic Acids Res.

A randomized phase II trial of bevacizumab vs. bevacizumab and erlotinib as first-line consolidation after carboplatin, paclitaxel, and bevacizumab in newly diagnosed patients with mullerian tumors.
Campos S, Matulonis U, Berlin S, Horowitz N, Liu J, Krasner C, Hang L, Zarwan C, Barry W, Colella T, Whalen C, Shoni M, Lundquist C, Birrer MJ, Penson R.
Int J Clin Oncol.

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model.
Garg S, Garg TK, Miousse IR, Wise SY, Fatanmi OO, Savenka AV, Basnakian AG, Singh VK, Hauer-Jensen M.
Antioxidants (Basel).

Alzheimer’s disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment
Ping-Chung Chen, Xian Han, Timothy I Shaw, Yingxue Fu, Huan Sun, Mingming Niu, Zhen Wang, Yun Jiao, Brett J W Teubner, Donnie Eddins, Lauren N Beloate, Bing Bai, Joseph Mertz, Yuxin Li, Ji-Hoon Cho, Xusheng Wang, Zhiping Wu, Danting Liu, Suresh Poudel, Zuo-Fei Yuan, Ariana Mancieri, Jonathan Low, Hyeong-Min Lee, Mary H Patton, Laurie R Earls, Elizabeth Stewart, Peter Vogel, Yawei Hui, Shibiao Wan, David A Bennett, Geidy E Serrano, Thomas G Beach, Michael A Dyer, Richard J Smeyne, Tudor Moldoveanu, Taosheng Chen, Gang Wu, Stanislav S Zakharenko, Gang Yu, Junmin Peng
Nature Ageing

A phase II evaluation of temsirolimus with carboplatin and paclitaxel followed by temsirolimus consolidation in clear cell ovarian cancer: An NRG oncology trial.
Farley JH, Brady WE, O’Malley D, Fujiwara K, Yonemori K, Bonebrake A, Secord AA, Stephan JM, Walker JL, Nam JH, Birrer MJ, Gershenson DM.
Gynecol Oncol.

Hepatitis C virus non-structural protein NS3 unfolds viral G-quadruplex RNA structures.
Belachew B, Gao J, Byrd AK, Raney KD.
J Biol Chem.

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer.
Urbaniak A, Reed MR, Heflin B, Gaydos J, Piña-Oviedo S, Jędrzejczyk M, Klejborowska G, Stępczyńska N, Chambers TC, Tackett AJ, Rodriguez A, Huczyński A, Eoff RL, MacNicol AM.
Biomed Pharmacother. 2022

Small molecule SJ572946 activates BAK to initiate apoptosis.
Sekar G, Singh G, Qin X, Guibao CD, Schwam B, Inde Z, Grace CR, Zhang W, Slavish PJ, Lin W, Chen T, Lee RE, Rankovic Z, Sarosiek K, Moldoveanu T.
iScience. 2022

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study.
Casablanca Y, Wang G, Lankes HA, Tian C, Bateman NW, Miller CR, Chappell NP, Havrilesky LJ, Wallace AH, Ramirez NC, Miller DS, Oliver J, Mitchell D, Litzi T, Blanton BE, Lowery WJ, Risinger JI, Hamilton CA, Phippen NT, Conrads TP, Mutch D, Moxley K, Lee RB, Backes F, Birrer MJ, Darcy KM, Maxwell GL.
Cancers (Basel).

Doctor of Philosophy students who passed their candidacy exams in the last year received their white coats at the Graduate School Research Induction Ceremony. Students from the Biochemistry and Molecular Biology Department who received their white coats were Clara Stiefel and Jessica Kelliher, both mentored by Justin Leung, Ph.D., Matthew Thompson, mentored by Alicia Byrd, Ph.D., Haven Griffin, mentored by Giulia Baldini, M.D., Ph.D., and Jake Edmonson, mentored by Alan Tackett, Ph.D. and Brian Koss, Ph.D. Congratulations to all!

Similar 5F-APINACA Metabolism between CD-1 Mouse and Human Liver Microsomes Involves Different P450 Cytochromes.
Crosby SV, Ahmed IY, Osborn LR, Wang Z, Schleiff MA, Fantegrossi WE, Nagar S, Prather PL, Boysen G, Miller GP.
Metabolites.

Monitoring helicase-catalyzed unwinding of multiple duplexes simultaneously.
Thompson MD, Malone EG, Byrd AK.
Methods Enzymol.

Alignment of helicases on single-stranded DNA increases activity.
Ozaslan D, Byrd AK, Belachew B, Raney KD.
Methods Enzymol.