EZH2 loss during metabolic stress drives restoration of MHC class I machinery in melanoma.
Edmondson JL, Reed MR, Fil D, Heflin B, McKinnon A, Bauer MA, Morehead LC, Avaritt NL, Phillips M, Taverna SD, Tackett AJ, Koss B.
iScience. 2025
Congratulations to Matthew Thompson, Ph.D., on his successful defense of his dissertation entitled, “DNA Helicase B (HELB) and DNA secondary structures at the DNA replication fork.” Dr. Thompson was mentored by Alicia Byrd, Ph.D. He will be an Assistant Professor of Chemistry and Lyon College this fall.
We’re excited to share highlights from the recent Graduate Student Association (GSA) Closing Ceremony, where several outstanding graduate students and staff members were honored for their leadership and dedication:
Mrs. Kathy Carlson, Education Coordinator, received the Legacy of Service Award in recognition of her long-standing commitment and unwavering support of the Graduate Student Association (GSA) .
Reham Sewilam, fourth-year Ph.D. student and GSA President, received both the Visionary Leadership Award and the Change Maker Award for her pioneering efforts and exceptional leadership in creating new initiatives to support graduate students at UAMS in both educational and non-educational levels.
Lokesh Akana, third-year Ph.D. student and GSA Treasurer, was honored with the Heart and Hustle Award for his enthusiastic contributions and dedication to the GSA mission.
Sanjay Adhikary, second-year Ph.D. student and GSA Secretary, received the Exemplary Service Award for his growing contributions and active involvement in the GSA mission.
Congratulations to all awardees for their incredible work and commitment to the graduate student community!
Rare SNP in the HELB gene interferes with RPA interaction and cellular function of HELB.
Osei B, May BH, Beard JS, Thompson MD, Alkam D, Zafar MK, Bergstrom E, Byrum SD, Enemark EJ, West KL, Byrd AK.
NAR Mol Med. 2025
Structure of the Saccharolobus solfataricus GINS tetramer.
Shankar S, Enemark EJ.
Acta Crystallogr F Struct Biol Commun. 2025
A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.
Klein M, Das A, Bera SC, Anderson TK, Kocincova D, Lee HW, Wang B, Papini FS, Marecki JC, Arnold JJ, Cameron CE, Raney KD, Artsimovitch I, Götte M, Kirchdoerfer RN, Depken M, Dulin D.
Nucleic Acids Res. 2025
Stress During Lactation: A Hidden Link to Offspring Bone Health.
Chandrashekar R, Mulakala BK, Gurung M, Venna G, Rearick JR, Onyekweli B, Ruebel ML, Dada-Fox J, Zeledon JA, Talatala R, Rodriguez K, Osborn LR, Bishop MG, Smith B, Stephens KE, Lucas EA, Yeruva L.
Calcif Tissue Int. 2025
Biomolecular condensates control and are defined by RNA-RNA interactions that arise in viral replication.
Aierken D, Zhang V, Sealfon R, Marecki JC, Raney KD, Gladfelter AS, Joseph JA, Roden CA.
Res Sq [Preprint]. 2025
Congratulations to Thomas Williams for winning the award for the best graduate student poster at the Winthrop P. Rockefeller Cancer Institute Retreat. Thomas’ poster was entitled, “Defining the role for PCK2 i T-cell metabolic plasticity in the solid tumor microenvironment” Thomas is a first year graduate student in the lab of Brian Koss, Ph.D.
Congratulations to Jake Edmondson, Ph.D., on his successful defense of his dissertation entitled, “Enhancing the cancer immunotherapy response through mechanisms of epigenetic control and endoplasmic reticulum stress.” Dr. Edmondson was mentored by Alan Tackett, Ph.D., and Brian Koss, Ph.D. He is an M.D./Ph.D. student who will return to medical school this summer.
GLP-1 receptor agonists in the context of cancer: the road ahead.
Miousse IR.
Am J Physiol Cell Physiol. 2025
Structural basis of BAK sequestration by MCL-1 in apoptosis.
Srivastava S, Sekar G, Ojoawo A, Aggarwal A, Ferreira E, Uchikawa E, Yang M, Grace CR, Dey R, Lin YL, Guibao CD, Jayaraman S, Mukherjee S, Kossiakoff AA, Dong B, Myasnikov A, Moldoveanu T.
Mol Cell. 2025
By Marty Trieschmann
April 22, 2025 | Molecular Cell publishes UAMS comprehensive structural biology study of MCL-1:BAK complex found in most cancers
A research team led by UAMS Winthrop P. Rockefeller Cancer Institute scientist, Tudor Moldoveanu, Ph.D., has uncovered novel insights into one of the body’s most fundamental processes impacting the development of cancer. Known as apoptosis, the research on the process of programmed cell death was published April 4 in the high-impact journal Molecular Cell.
“At a high level, our research tackles a central mechanism of cell death known as apoptosis,” said Moldoveanu, an associate professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology and co-leader of the Cancer Institute’s Cancer Therapeutics Research Program.
“Apoptosis is a fundamental biological process that supports our health,” he said. “Our bodies need to get rid of cells that are too old or damaged to work properly. If those cells keep hanging around, they can harm us and lead to cancer and other conditions.”
Moldoveanu’s study focuses on the protein complex MCL-1:BAK which blocks apoptosis when formed and is a common target for drug makers.
“There are four other known proteins similar to MCL-1 that inhibit apoptotic cell death that we know of, and MCL-1 is one of the worst that shows up in a lot of cancers,” Moldoveanu said. “It’s one of the most upregulated proteins in cancer that makes it harder for cell death to happen and is a proven recipe for growing tumors in cancer.”
In multiple myeloma, MCL-1 is responsible for more than 40% of new cases and more than 70% of relapsed, refractory cases. BAK is a pro-death protein that initiates apoptosis when activated by cancer therapies and often interacts with MCL-1 blocking its pro-apoptotic role.
For the first time, drug makers now have an atomic level view of the MCL-1:BAK protein complex. Moldoveanu’s team used an integrated structural biology approach with nuclear magnetic resonance (NMR) spectroscopy, cryo-electron microscopy (cryo-EM) and X-ray crystallography, to provide the most detailed characterization of the molecular structure of the complex to date.
After testing select highly potent drugs designed to inhibit MCL-1 in a reconstituted MCL-1:BAK complex in the lab, the results surprised even Moldoveanu.
“One of the most surprising findings is that MCL-1 inhibitors are not very good in neutralizing the MCL-1:BAK complex, requiring high doses to initiate cell death. Our study underscores the need to design superior MCL-1 inhibitors.”
Moldoveanu is the lead author of the study between his lab in the UAMS Department of Biochemistry and Molecular Biology and collaborators at St. Jude Children’s Research Hospital, the University of Chicago, the University of Arkansas in Fayetteville and École Polytechnique Fédérale de Lausanne.
“Among the cancer therapies available to us, we have very few inhibitors to regulate cell death in patients with cancer,” Moldoveanu said.
“The problem is that current inhibitors targeting MCL-1 also impact organs and tissues, such the heart and cells that line the blood vessels,” he added. “These cells are highly susceptible to toxicity from cancer chemotherapy in general, so the issue is how to administer MCL-1 inhibitors to initiate cell death safely and in a more targeted way that doesn’t go everywhere in the body.
“Now that we have a better view of how this complex looks and forms and that these drugs are not as effective as we imagined, we can move forward with designing future therapies to have better potency and bioavailability in neutralizing this pathway,” said Moldoveanu.
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.
Lokesh Akana, a Biochemistry and Molecular Biology Ph.D. student in Dr. Adam Wolfe’s lab, won first place in the 3 Minute Thesis competition for his presentation on SETD2 as a Horcrux in radiation resistant rectal cancer.
Several Biochemistry and Molecular Biology Department trainees won awards for their poster presentations.
