Dr. Alan Tackett, Professor of Biochemistry and Molecular Biology, has been invited to serve as a standing member of the NIH Mechanisms of Cancer Therapeutics-1 (MCT1) Study Section, one of the major review boards for evaluation of cancer research by the Center for Scientific Review. The four-year appointment recognizes Dr. Tackett, who also serves as the Scharlau Family Endowed Chair in Cancer Research at UAMS, as a leader in this field. Congratulations to Dr. Tackett.

Neonatal Diet Impacts Circulatory miRNA Profile in a Porcine Model.

Carr LE, Bowlin AK, Elolimy AA, Byrum SD, Washam CL, Randolph CE, MacLeod SL, Yeruva L.

Front Immunol. 2020

---

Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin.

Dong C, West KL, Tan XY, Li J, Ishibashi T, Yu CH, Sy SMH,Leung JWC, Huen MSY.

Proc Natl Acad Sci 2020

---

Novel advances in biotransformation and bioactivation research-2019 year in review.

Khojasteh SC, Driscoll JP, Jackson KD, Miller GP, Mitra K, Rietjens IMCM, Zhang D.

Drug Metab Rev. 2020

Congratulations to Dr. Grover Miller, Professor of Biochemistry and Molecular Biology, on his appointment to the Xenobiotic and Nutrient Disposition and Action (XNDA) Study Section in the National Institutes of Health’s Center for Scientific Review. Dr. Miller will serve a four-year term on the panel, whose members are selected for their excellence and achievement in their scientific discipline. At UAMS, Dr. Miller and his team develop and apply new and powerful strategies to better assess drug liabilities that cause significant adverse drug events including cardio- and hepato-toxicity.

Congratulations to postdoctoral fellow Maroof Zafar and his co-authors, Lindsey Hazeslip, Zain Chauhan, and Alicia Byrd.  Cover art by Lindsey Hazeslip for their recent article on regulation of expression by non-canonical G-quadruplexes was selected for the cover of the July 2020 issue of Biochemistry.

By Susan Van Dusen

LITTLE ROCK — A research team led by cancer researcher Justin Leung, Ph.D., at the University of Arkansas for Medical Sciences (UAMS) has uncovered the role of the protein RNF168 in DNA damage repair and shown how mutations of the protein affect people with a rare genetic condition.

The study titled “Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination” was published in the May 18 issue of the open-access journal Nature Communications.

“Every day our cells are subjected to environmental sources of DNA damage, such as ultraviolet radiation and toxic chemical exposure. If left unrepaired, these damages can accumulate, leaving mutations in our DNA and ultimately cause cells to become cancerous,” said Leung, assistant professor in the UAMS College of Medicine Department of Radiation Oncology.

In most cases, this damage is detected and repaired by a tightly regulated method involving many proteins. To develop better cancer therapies, researchers such as Leung strive to understand the regulation of DNA damage and repair by sensitizing cells to radiation therapy and chemotherapy drugs that target DNA.

“Our lab studies the repair of double stranded breaks, where both strands of DNA are broken apart completely. When a double strand break occurs, a cascade of protein activity is set off to try to resolve the damage,” Leung said.

Mutations in one of these proteins, RNF168, have been found in patients with RIDDLE syndrome, a rare genetic disorder that increases a person’s predisposition to blood cancer and is characterized by several attributes:

• Susceptibility to DNA damaging agents
• Immunodeficiency, or failure of the immune system to protect the body from infection
• Developmental abnormalities
• Learning disabilities

RNF168 adds a small signaling molecule called ubiquitin onto a subunit of chromatin, where we store our genetic information. The ubiquitin signal brings repair proteins to DNA double strand breaks. However, exactly how RNF168 recognizes the specific target remains unclear.

Using molecular and structural analysis methods, Leung’s team uncovered crucial components of RNF168 and chromatin required for the implementation of repair pathways in response to DNA damage. Their findings suggest that a recognition between RNF168 and chromatin is required to activate the downstream DNA repair processes.

“RNF168 is a central DNA damage response protein. Understanding the precise mechanisms by which it activates its targets is essential for understanding how the DNA damage response goes awry. Our results help demystify the role of RNF168 in proper DNA damage repair and understand the implications of RNF168 mutations such as those seen in RIDDLE syndrome,” Leung said.

UAMS authors for this study included Jessica Kelliher, B.S., research assistant, and Kirk West, Ph.D., postdoctoral fellow.

Alan Diekman, Ph.D., was honored as the 2020 Master Teacher in recognition of his work with first-year medical students. When College of Medicine students are asked about their best teachers, Diekman’s name comes up often. As director of the Molecules to Cells course, Diekman teaches first-year students and works with other faculty to ensure the students gain a firm grasp of biochemistry, cell biology and genetics – including complex concepts that many medical students nationwide struggle to grasp.

“Most importantly, he has convinced students that understanding molecular and cellular mechanisms is an important part of their medical training,” Department of Physiology and Biophysics Chair Michael Jennings, Ph.D., wrote in a letter of support for Diekman, who has served on the faculty since 2002.

“The word ‘outstanding’ may underestimate the quality of Dr. Diekman’s teaching effort, ability and outcomes,” Biochemistry and Molecular Biology Chair Kevin Raney, Ph.D., wrote in his nomination letter. “He is a superb communicator who treats students respectfully, while maintaining high expectations. Dr. Diekman also sets high standards for his colleagues, thereby improving the quality of teaching of those around him.”

James Graham, M.D., executive associate dean for academic affairs in the college, also wrote in support, noting strong performance by UAMS students in areas of the notoriously difficult United States Medical Licensing Exam Step 1 that are covered in Diekman’s course, as well as improved overall performance on the exam in recent years. Diekman has been instrumental in major curriculum revisions that change how first- and second-year medical students prepare for their clinically focused training.

“I am very honored by this recognition from my colleagues, and I thank them for their past support,” said Diekman. “The privilege of educating our medical students in the complex disciplines of biochemistry, cell biology and genetics is both challenging and fulfilling. My goal is to provide our students with a firm foundation in these disciplines, not just for their sake, but also for that of their future patients.”

Genome Maintenance by DNA Helicase B.

Selective Survival of Sim1/MC4R Neurons in Diet-Induced Obesity.

Dual mechanisms suppress meloxicam bioactivation relative to sudoxicam.

 

Advances in the study of drug metabolism – symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX).

The UAMS Graduate School held a virtual hooding ceremony which you can read more about here. The Biochemistry and Molecular Biology Department graduated three students last year. Tresor Mukiza, Ph.D. is now a postdoctoral fellow in Joseph Opferman’s lab at St. Jude Children’s Research Hospital. Tresor’s mentor at UAMS was Wayne Wahls. Eugene Nyamugenda, Ph.D. is now a postdoctoral fellow in Ravi Allada’s lab at Northwestern University in the Department of Neurobiology. Eugene’s mentor at UAMS was Giulia Baldini. Bradley Shields, M.D., Ph.D. is beginning a residence in dermatology at Intermountain Medical Center and the University of Pittsburgh Medical Center. Bradley’s mentor at UAMS was Alan Tackett.

Alan Tackett, a professor in the Department of Biochemistry and Molecular Biology, was featured in a story on KARK this morning about clinical trials at UAMS.