News

Bhuvan Award

Congratulations to the winners of the Bhuvan Award for Excellence in Biochemistry Research at Student Research Day 2023.

1^st place – Jessica Kelliher – Department of Biochemistry and Molecular Biology

2^nd place – Farhana Sumya – Department of Physiology and Cell Biology

3^rd place – Matthew Thompson – Department of Biochemistry and Molecular Biology

The Bhuvan Award for Excellence in Biochemistry Graduate Research was established by colleagues in the Colleges of Medicine and Pharmacy in memory of Dr. Bhuvaneswaran who was a member of the faculty in the Department of Biochemistry and Molecular Biology. Dr. Bhuvan, as students and colleagues alike affectionately knew him, was a superb experimentalist and the laboratory provided the stimulation for continued learning throughout his life. Because his culture revered the teacher/mentor most of all, his highest aspiration was to gain respect as a teacher. In addition to his formal contributions to graduate and medical student education, fostering an interest and love of science in young scientists was an important aspect of Dr. Bhuvan’s life. All graduate students that use some aspect of Biochemistry in their research are eligible for the award.

February 2023 Publications

Nonsense-Mediated mRNA Decay as a Mediator of Tumorigenesis.
Nagar P, Islam MR, Rahman MA.
Genes (Basel).

Alicja Urbaniak, Alan Tackett, and Billie Heflin

The mycelium of the Trametes versicolor synn. Coriolus versicolor (Turkey tail mushroom) exhibit anti-melanoma activity in vitro.
Lowenthal R, Taylor M, Gidden JA, Heflin B, Lay JO Jr, Avaritt N, Tackett AJ, Urbaniak A.
Biomed Pharmacother.

Lauren Clai Morehead

women in a mustard yellow with white daisy shirt smiling — Clai Morehead

Clai is a 6th year MD/Ph.D student in her 4th year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Alan Tackett and Dr. Isabelle Racine Miousse

She has a BS in Chemistry from Southern Arkansas University

Research Interest Statement

Immune checkpoint inhibitor therapy has drastically improved outcomes in treating cancer, particularly in melanoma. However, half of melanoma patients are resistant to treatment. One mechanism used by tumor cells to evade immune attack is to down-regulate major histocompatibility complex (MHC) class I molecules, which are required for cytotoxic CD8⁺ T-cells to eliminate cancer cells. To increase immunotherapeutic efficacy, it is critical to identify how to restore MHC-I expression on cancer cells so that tumor antigens are presented. We found that resveratrol elevated MHC-I expression, thereby improving CD8⁺ T-cell killing. Through proteomic interrogation, we identified the STING pathway as a potential mechanism of action. Further studies indicated that resveratrol-mediated STING signaling induced MHC-I expression through both interferon-independent and dependent pathways. Our results have uncovered the ability of STING to induce MHC-I expression independent of interferon signaling, broadening the potential of STING activation as a tool to improve immune checkpoint blockade.

Something Notable about Time as a Graduate Student

On my desk I have two quotes, one is from Joan Didion from The Year of Magical Thinking (“Read, learn, work it up, go to the literature. Information is control) and the other is from Merlin Sheldrake from Entangled Life (“What’s astonishing is the gulf between what we expect to find and what we find when we actually look”). Over the course of my studies, I’ve learned that being a scientist is an interplay between empowering yourself to ask good questions through information and expecting that the answers could be far away from what you imagined. I’m taking Didion’s quote a bit out of context for my purposes, but I relate to it in context as well.

Career Goals

As an MD/PhD student, my immediate tasks proceeding my PhD are returning to medical school to finish my medical education and then moving on to medical residency. My goal is to match into a dermatology residency program. I would like to continue contributing to research throughout the rest of my medical training. Post-residency, I plan on seeking an academic position and splitting my time between clinic and research. I would like to focus on inflammatory skin diseases and clarify targetable pathways for treatment. Health equity is also important to me. Currently I’m reading Health Communism by Artie Vierkant and Beatrice Adler-Bolton, and it really forces me to reconcile to the negative social processes that my fields help enable. When I become a physician-scientist, using my insight on both fields and how they serve as a source of knowledge and beneficence but also of capital, I plan on being involved in work progressing social justice initiatives to reach better health for all.

Experiment or Technique You would Most Like to Do

Honestly, I’m less interested in the performance of the experiments themselves, I’m more so into developing questions and plans to answer them. So, I’d like to do whatever answers the question.

Fun Fact

I like kpop; I can list all 22 members of NCT in age-order! I implore you to listen to “Sticker” by NCT 127.

Publications

The evolving clinical landscape for dendritic cell vaccines and cancer immunotherapy MJ Cannon, MS Block, LC Morehead, KL Knutson Immunotherapy 11 (2), 75-79

Further clinical advancement of dendritic cell vaccination against ovarian cancer LC Morehead, MJ Cannon Annals of research hospitals 2

Differences in cell death in methionine versus cysteine depletion KF Wallis, LC Morehead, JT Bird, SD Byrum, IR Miousse Environmental and molecular mutagenesis 62 (3), 216-226

Awards

Best Talk – 35^th National MD/PhD Conference Diversity Award – 35^th and 37^th National MD/PhD Conference Melanoma Research Foundational Medical Student Award

January 2023 Publications

Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis.
Griffin H, Sullivan SC, Barger SW, Phelan KD, Baldini G.
Int J Mol Sci.

Alzheimer’s disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment.
Chen PC, Han X, Shaw TI, Fu Y, Sun H, Niu M, Wang Z, Jiao Y, Teubner BJW, Eddins D, Beloate LN, Bai B, Mertz J, Li Y, Cho JH, Wang X, Wu Z, Liu D, Poudel S, Yuan ZF, Mancieri A, Low J, Lee HM, Patton MH, Earls LR, Stewart E, Vogel P, Hui Y, Wan S, Bennett DA, Serrano GE, Beach TG, Dyer MA, Smeyne RJ, Moldoveanu T, Chen T, Wu G, Zakharenko SS, Yu G, Peng J.
Nat Aging.

Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.
Moldoveanu T.
Bioessays.

Oncolytic strategy using new bifunctional HDACs/BRD4 inhibitors against virus-associated lymphomas.
Chen J, Wang Z, Phuc T, Xu Z, Yang D, Chen Z, Lin Z, Kendrick S, Dai L, Li HY, Qin Z.
PLoS Pathog.

Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer.
Penson RT, Ambrosio AJ, Whalen CA, Krasner CN, Konstantinopoulos PA, Bradley C, Matulonis UA, Birrer MJ.
Oncologist.

LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma.
Sato S, Gillette M, de Santiago PR, Kuhn E, Burgess M, Doucette K, Feng Y, Mendez-Dorantes C, Ippoliti PJ, Hobday S, Mitchell MA, Doberstein K, Gysler SM, Hirsch MS, Schwartz L, Birrer MJ, Skates SJ, Burns KH, Carr SA, Drapkin R.
Sci Rep.

Biochemistry Collaborations

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.

December 2022 publications

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.

U.S. Defense Department Awards UAMS Cancer Researcher $760,000 to Study Aggressive Type of Lymphoma

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.

Congratulations Dr. Belachew

Dr. Belachew with his committee — Dr. Belachew with members of his advisory committee. Craig Forrest, Ph.D., Binyam Belachew, Ph.D., Kevin Raney, Ph.D., Robert Eoff, Ph.D., Tim Chambers, Ph.D., and Mari Davidson, Ph.D.

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.

November 2022 Publications

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.

October 2022 Publications

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.