Congratulations to Megan Reed who successfully defended her Ph.D. dissertation entitled “Mechanisms of DNA damage tolerance in glioblastoma” on April 28. Megan was a student in the laboratory of Dr. Robert Eoff and will begin a postdoctoral fellowship in July under the mentorship of Dr. Analiz Rodriguez and Dr. Alan Tackett. Dr. Reed’s postdoctoral studies will be funded by Health Sciences Innovation and Entrepreneurship TL1 program from the Translational Research Institute.
News
UAMS Cancer Researcher Receives $1.1 Million as Part of NIH Grant at University of Arkansas, Fayetteville
A National Institutes of Health (NIH) grant will allow UAMS researcher Isabelle Racine Miousse, Ph.D., to ramp up her study of a nutrient that may have a role in the effectiveness of immunotherapy for cancer patients.
Miousse will receive $220,000 per year for up to five years as one of four project leaders at the Arkansas Integrative Metabolic Research Center, a new NIH-funded Center of Biomedical Research Excellence (COBRE) at the University of Arkansas, Fayetteville. The university announced April 6 that the center will receive $10.8 million over five years.
The funding will support Miousse’s preclinical cancer studies involving methionine, an amino acid important for human growth and derived primarily from consuming meat.
Miousse, an assistant professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology, will test whether reducing dietary methionine can improve results of immunotherapy drugs used to treat melanoma patients.
“This has never been tried in combination with immunotherapy drugs,” Miousse said, noting that immunotherapy alone works remarkably well, but only for 50% of melanoma patients. “So far the results of this research are very encouraging, and I am hopeful that this next phase of study will take us into clinical trials.”
Unlike most cancer treatments, she notes, this one has beneficial side effects.
“Reducing methionine in the diet promotes the metabolism of fats and sugars in animal models,” Miousse said. “Methionine restriction could fight cancer and improve general health at the same time.”
Miousse’s work has been supported by the UAMS Translational Research Institute’s two-year KL2 Mentored Research Career Development Award for promising early career researchers. The KL2 provides salary support, research seed funding of $50,000 and translational research training. The institute is supported by a Clinical and Translational Science Award from the NIH National Center for Advancing Translational Sciences.
Alan Tackett Named Arkansas Research Alliance Fellow
Edward T.H. Yeh, M.D., a cardiologist renowned in the field of onco-cardiology, was named an ARA Scholar, and Alan Tackett, Ph.D., a cancer researcher widely recognized for his work in cancer biomarker discovery, was honored as an ARA Fellow.
Yeh will receive $500,000 and Tackett will receive $75,000 to further their research.
“We are extremely proud to have both a new ARA Scholar and ARA Fellow at UAMS. The leadership demonstrated by Dr. Yeh and Dr. Tackett has made a valuable impact on research programs at UAMS. We are fortunate to have them in Arkansas and look forward to their future successes,” said Cam Patterson, M.D., MBA, UAMS Chancellor and UAMS Health CEO.
The ARA Scholars program helps recruit and support world-class researchers to universities where their work helps strengthen the competitiveness of the state.
The ARA Fellows program recognizes research leaders who are currently working in Arkansas at one of the state’s five research campuses.
“The ARA Scholars program is the cornerstone for our organization and bridges the gap between university research and economic development, while our Fellows program recognizes research leaders who have already made an impact in our state,” said Jerry Adams, ARA president. “We anticipate great things from both Dr. Yeh and Dr. Tackett as they build upon their outstanding research portfolios and explore new paths in the future.”
Yeh joined UAMS in 2020 as chair of the Department of Internal Medicine and the Nolan Family Distinguished Chair in Internal Medicine in the College of Medicine.
From 2000 to 2016, he served as professor and founding chair of the Department of Cardiology at the University of Texas MD Anderson Cancer Center in Houston, where he made seminal contributions to understanding the relationships between cancer, chemotherapy agents and heart disease. In 2012, his laboratory discovered that Topoisomerase 2b is the molecular basis of anthracycline-induced cardiotoxicity, upending decades of belief that toxicity to this chemotherapy drug was due solely to reactive oxygen species (ROS) generation.
Earlier, Yeh made important contributions in biochemistry, including the discovery of two ubiquitin-like proteins, SUMO/Sentrin and NEDD8. Both of these proteins are important in regulation of hypoxia-inducible factor stability, DNA repair, heart and lymphoid development, cancer pathogenesis, and sudden death and seizure disorders.
Tackett’s research involves using advanced technology to discover molecular pathways essential for the development of new therapies and finding new biological markers to assist in developing a personalized treatment for each patient’s specific needs.
He is deputy director of the UAMS Winthrop P. Rockefeller Cancer Institute, professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology and holder of the Scharlau Family Endowed Chair in Cancer Research.
In 2020, Tackett was awarded a $10.6 million grant from the National Institutes of Health (NIH) establishing the IDeA National Resource for Quantitative Proteomics as the first NIH National Resource in Arkansas, which serves biomedical researchers across the nation.
Binyam Belachew student highlight
Binyam is a GPIBS Ph.D. student in the Biochemistry and Molecular Biology track. He is a 5th-year student in the laboratory of Dr. Kevin Raney. He graduated from Wingate University with a Bachelor of Science in Biology.
Research Interest Statement
Hepatitis C is an infectious disease caused by Hepatitis C virus (HCV). Currently, 71 million people in the world are chronically infected with the virus and around 400, 000 people die each year of complications related to the infection. HCV, like Coronavirus, is an RNA virus. The RNA genome of HCV encodes for 10 different viral proteins, one of which is NS3 (non-structural protein 3). NS3 has both a protease and a helicase domain. The helicase domain of NS3 is essential for viral replication, however, its mechanism of action is not well understood. The HCV genome has conserved G-quadruplex (G4) forming sequences. G4 is formed when tandem repeats of Guanine resides interact with each other through Hoogsteen hydrogen bonding. Helicases of the same family as NS3 are reported to unfold G4RNA structures. Therefore, it is possible that NS3 could facilitate HCV replication by unfolding G4 secondary structures found within the HCV genome, and these secondary structures could stall the replication process if it remain folded. My project focuses on understanding the mechanism by which HCV-NS3 interacts with and unfolds HCV-G4RNA. By studying how NS3 regulates HCV-G4RNA, we might find processes or factors that could serve as targets for anti-HCV agents to suppress the replication of various strains of HCV.
Something Notable about Time as a Graduate Student
Over the last four years I have been in Raney’s lab, I have been fortunate to attend several domestic and international academic conferences where I presented my work and learned from the works of others. By going to conferences, I was able to meet professionals and expand my network.
Career Goals
I would like to pursue a career in research and teaching.
Experiment or Technique You Would Most Like to Do
Computational modeling
Fun fact
I like running, hiking, and biking.
Publications
Lakkaniga, N. R., N. Gunaganti, L. Zhang, B. Belachew, B. Frett, Y. K. Leung, and H. Y. Li. 2020. Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation. Eur.J.Med.Chem. 206:112691.
Lakkaniga, N. R., L. Zhang, B. Belachew, N. Gunaganti, B. Frett, and H. Y. Li. 2020. Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression. Eur.J.Med.Chem. 203:112589. doi:S0223-5234(20)30561-4 [pii];10.1016/j.ejmech.2020.112589 [doi].
Dr. Leung presenting for Research Antipasto
Research and Innovation is hosting the next Research Antipasto monthly event (informal online networking, casual mentoring, happy hour-ish get-together) at noon on April 6, 2021. Justin Leung, Ph.D., M.Sc. will host. Justin is an assistant professor in the Department of Radiation Oncology with a secondary appointment in the Department of Biochemistry and Molecular Biology. Justin recently received his 3rd NIH R01. Justin’s research interests include chromatin biology, epigenetics, DNA damage, and more.
On the first Tuesday of each month, Research Antipasto’s host will share career experiences, stories, answer questions, advise, astound, and amaze…for 30 to 60 minutes (or until we all have to catch another meeting). Just log in, have fun, and get to know others in the research community! Hosts are posted on the research calendar.
UAMS’ Justin Leung, Ph.D., Receives $1.47 million Grant from National Cancer Institute to Study DNA Damage Regulation
Leung’s project is a collaboration with Robert Eoff, Ph.D., a professor in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine. Both Leung and Eoff are researchers in the UAMS Winthrop P. Rockefeller Cancer Institute.
“Our work will potentially provide a fundamental understanding of the molecular mechanism of DNA damage regulation in our body and also reveal potential targets for cancer therapeutic development,” said Leung, an assistant professor in the UAMS College of Medicine Department of Radiation Oncology.
Work on the NCI grant, “Mechanistic Characterization of Cell Cycle-Dependent DNA Repair,” focuses on dissecting the molecular mechanism on cell cycle-regulated DNA repair, specifically during early DNA replication. Leung and Eoff hope to identify a key group of proteins known as a histone-mark reader that work together to protect our genetic material from DNA damage.
The NCI grant comes on the heels of Leung receiving a four-year, $792,000 American Cancer Society Research Scholar grant to study DNA repair mechanisms. He will use that grant to investigate how signaling molecules on chromatin interact with proteins that repair broken DNA during replication.
In September 2020, the National Institute of General Medical Sciences awarded Leung a $1.9 million grant in support of the researcher’s roadmap project, “Deciphering the Chromatin-based DNA Damage Response Pathway.”
Explore career options with job simulations
Are you a student or postdoc who is uncertain about your career goals? InterSect has job simulations for a wide variety of Ph.D. level scientific career.
Allie Schleiff highlighted by ASPET for work on meclofenamate bioactivation
Congratulations to graduate student Mary “Allie” Schleiff on her selection as the Drug Metabolism and Disposition Highlighted Trainee Author for February 2021. Allie is a Ph.D. student in the laboratory of Dr. Grover Paul Miller. The Drug Metabolism and Disposition article that earned her selection as a Highlighted Trainee Author is titled “Significance of Multiple Bioactivation Pathways for Meclofenamate as Revealed through Modeling and Reaction Kinetics.”
February publications
Ketkar A, Smith L, Johnson C, Richey A, Berry M, Hartman JH, Maddukuri L, Reed MR, Gunderson JEC, Leung JWC, Eoff RL. Nucleic Acids Res.
Differences in cell death in methionine versus cysteine depletion.
Wallis KF, Morehead LC, Bird JT, Byrum S, Miousse IR. Environ Mol Mutagen.
Frett B, Saha D, Ryan KR, Lakkaniga NR, Smith EL. ChemMedChem.
Bone remineralization of lytic lesions in multiple myeloma – The Arkansas experience.
Mohan M, Kumar M, Samant R, Van Hemert R Jr, Tian E, Desai S, van Rhee F, Thanendrarajan S, Schinke C, Suva LJ, Sharma S, Milad M, Kendrick S, Zangari M. Bone.
Inhibition of Kpnβ1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer.
Chi RA, van der Watt P, Wei W, Birrer MJ, Leaner VD.BMC Cancer.
Tackett Named Deputy Director of UAMS Winthrop P. Rockefeller Cancer Institute
Highly regarded for his research in cancer biomarker discovery, Tackett is a professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology. He previously served as associate director of basic research for the UAMS Cancer Institute and holds the Scharlau Family Endowed Chair in Cancer Research.
Tackett is principal investigator for the National Institutes of Health (NIH) (R24) National Resource for Quantitative Proteomics and the NIH (P20) Center of Biomedical Research Excellence in systems biology. His National Cancer Institute-funded research program focuses on the use of cutting-edge systems approaches to identify biomarkers and novel pathways of resistance to cancer therapies.
Tackett will work directly with Michael Birrer, M.D., Ph.D., Cancer Institute director, to expand the research and clinical missions of the Cancer Institute.
“Dr. Tackett’s expertise and insightfulness will be a huge benefit to the Cancer Institute as we continue to grow and move toward our goal of National Cancer Institute Designation,” Birrer said.