By Tamara Robinson

Aug. 1, 2025 | Sydnye Shuttleworth, a student in the University of Arkansas for Medical Sciences (UAMS) College of Medicine and an affiliate trainee member of the Winthrop P. Rockefeller Cancer Institute, has been awarded a prestigious fellowship award for aspiring physician-scientists from the National Institutes of Health (NIH) National Cancer Institute (NCI).

Shuttleworth, who is pursuing a doctoral degree in the UAMS Graduate School in addition to a medical degree, is the first M.D./Ph.D. student at UAMS to receive the highly competitive Ruth L. Kirschstein National Research Service Award (NRSA) from the NCI. She joins an elite group across the country and a small group from UAMS who have received NRSA awards from one of the NIH institutes.

The $189,128 award, referred to as an F30 NRSA fellowship, provides four years of funding for Shuttleworth’s tuition, a stipend and an institutional allowance to support her research training.

“Ms. Shuttleworth’s NRSA fellowship is focused on the rapidly expanding field of engineering immune cells to be more effective and efficient at eliminating cancer cells, particularly those in solid tumors,” said Alan Tackett, Ph.D., deputy director of the UAMS Winthrop P. Rockefeller Cancer Institute and executive associate dean for basic research in the UAMS College of Medicine. “This specific area of research has the potential to transform how we utilize immunotherapies to treat patients with cancer.”

“Sydnye is one of those trainees who just doesn’t let up — in the best way,” said Shuttleworth’s mentor, Brian Koss, Ph.D., an assistant professor in the Department of Biochemistry and Molecular Biology. “She is driven, deeply committed, and always thinking about how her work can make a real impact. That kind of focus is exactly what you want in a future physician-scientist, and it’s no surprise she has already earned competitive funding to support her research. She raises the bar for everyone around her, including me.”

Read more about Sydnye.

Untargeted CUT&Tag reads are enriched at accessible chromatin and restrict identification of potential G4-forming sequences in G4-targeted CUT&Tag experiments.
Thompson MD, Byrd AK.
Nucleic Acids Res. 2025

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G-quadruplex and i-motif DNA structures form in the promoter of the key innate immune adaptor MYD88.
Brown S, Swafford K, McCrury M, Nasrin F, Gragg CQ, Chavan A, Roy Choudhury S, Dickerhoff J, Yang D, Kendrick S.
Cell Rep Phys Sci. 2025

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Monensin and Its Analogs Exhibit Activity Against Breast Cancer Stem-Like Cells in an Organoid Model.
Urbaniak A, Heflin B, Siegel E, Reed MR, Nix JS, Yee EU, Jędrzejczyk M, Klejborowska G, Stępczyńska N, Huczyński A, Nagalo MB, Chambers TC, Post S, Eoff RL, MacNicol MC, Tiwari AK, Kelly T, Tackett AJ, MacNicol AM.
bioRxiv [Preprint]. 2025

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The XPO1 Inhibitor Eltanexor Modulates the Wnt/β-Catenin Signaling Pathway to Reduce Colorectal Cancer Tumorigenesis.
Evans AE, Afroz S, Magstadt A, Kasi A, Dixon DA.
Cancer Res Commun. 2025

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 at Lyon College this fall.

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

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Structure of the Saccharolobus solfataricus GINS tetramer.
Shankar S, Enemark EJ.
Acta Crystallogr F Struct Biol Commun. 2025

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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

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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

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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

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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.