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

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

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.

• First place:  Walter Saul Aragon-Ramirez, working in the lab of Dr. Vladimir Lupashin
• Second place:  Baku Acharya, working in the lab of Dr. Brendan Frett
• Third place:   Matthew Thompson, working in the lab of Dr. Alicia Byrd

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.

• Preeti Nagar, Ph.D., won the award for the best cancer research presentation for her poster, “Targeting RNA Processing Defects in Splicing Factor-Mutated Cancer” from the Winthrop P. Rockefeller Cancer Institute in the postdoctoral fellow, medical house staff, and fellows category. Dr. Nagar is a postdoctoral fellow in Dr. Mohammad Rahman’s lab.
• Matthew Thompson won first place for the best cancer research presentation for his poster, “HELB prevents excessive ssDNA formation following replication stress”, from the Winthrop P. Rockefeller Cancer Institute in the graduate student category. Matthew is a Ph.D. student in Dr. Alicia Byrd’s lab.
• Vy Nguyen won second place for the best cancer research presentation for her poster, “Rnd3 Drives Lung Cancer Metastatic Potential Through a ROCK1-Independent Mechanism”, from the Winthrop P. Rockefeller Cancer Institute in the graduate student category. Vy is a Ph.D. student in Dr. Katie Ryan’s lab.
• Matthew Thompson won third place in the Bhuvan Award for excellence in biochemistry research by a graduate student for his poster, “HELB prevents excessive ssDNA formation following replication stress”. Matthew is a Ph.D. student in Dr. Alicia Byrd’s lab.

Biochemistry and Molecular Biology graduate students Emory Malone and Reham Sewilam shared their artwork at Art for the Heart on April 15, 2025. Emory won the People’s Choice Award for her cross-stitch called Reflection. Congratulations Emory! Reham shared two two acrylic paintings titled Eclipse and Queen Cleopatra.

Art from the Heart partners with the Paulette and Jay Mehta Creative Writing Awards and the Department of Medical Humanities and Bioethics in the College of Medicine. This collaboration highlights the artistic talent across various disciplines and recognizes UAMS community members with the presentation of awards at the Art from the Heart reception. The event showcased over 40 creative works in a variety of art forms. This year’s works were submitted by UAMS staff, faculty, students, and their immediate family members.

Congratulations to Arkansas School for Mathematics, Sciences, and the Arts (ASMSA) senior Meera Patel and her UAMS graduate student mentors, Reham Sewilam and Bethany Paxton. Meera won multiple prestigious awards for her research exploring novel ways to battle cancer risks. Meera earned first place in the Medicine and Health Sciences division and was a finalist for the overall awards at the West Central Regional Science and Engineering Fair, which was held at ASMSA on February 27^th-28^th, 2025. Meera subsequently won first place in the Medicine and Health Sciences category at the 71^st annual Arkansas State Science and Engineering Fair, which was held at the University of Central Arkansas on April 4^th and 5^th. Additionally, Meera was awarded the Naval Science Award from the Office of the Navy for excellent student research. Meera also placed 5^th in the Arkansas Junior Science and Humanities Symposium and qualified for the National Symposium, which is a STEM competition for high school students sponsored by the Department of Defense.

Meera conducted her award-winning research in the laboratory of Dr. Robert Eoff in the Department of Biochemistry and Molecular Biology at UAMS. This research and training opportunity was supported by award 2341253 (to R.L.E.) from the National Science Foundation.