Dr. Miousse to present for CTSA Grand Rounds
News
Dr. Byrd receives Hornick Endowment Grant
Congratulations to Dr. Alicia Byrd on receiving research funding of $25,000 from the Hornick Endowment Grant Program. This award is for one (1) calendar year and will fund additional research related to Dr. Byrd’s grant entitled “The effect of rs75770066, a stroke associated single nucleotide polymorphism, on enzyme activity”.
Dr. Alicja Urbaniak receives Barton Pilot Grant
Congratulations to Dr. Alijca Urbaniak, Instructor in the Department of Biochemistry and Molecular Biology, on receiving research funding of $25,000 from the Barton Pilot Grant Program. This award is for one (1) calendar year to fund additional research related to Dr. Urbaniak’s grant entitled “Novel Monensin Analogs for the Treatment of Metastatic Breast Cancer”.
Oleg Karaduta & Mari Davidson invited as Guest Editors
Dr. Oleg Karaduta and Dr. Mari Davidson invite contributions to a special issue of applied sciences on the Evolution of Modern Molecular Biology Applications.
Forty years ago, when relatively powerful microprocessors first became available, many young entrepreneurs were inspired to create companies, platforms, and programming tools that helped make computing available to everyone. This in turn helped spark the information revolution. Today, thanks to the increasing sophistication, speed, and power of computer modeling and other new tools, we are on the brink of another revolution — this time in bioscience.
The aim of this Special Issue, therefore, is to offer a platform for scientists working on the different aspects of Molecular Biology; fusion of classical methods with novel approaches drives human progress, and it is this belief that fuels our optimism in that direction.
We invite you to submit manuscripts addressing novel uses of classical techniques in molecular biology and possible applications of these methods in future medical and life science research for a compilation of our current knowledge into a comprehensive issue.
Congratulations Dr. Taylor!
Congratulations to Erin Taylor who successfully defended her Ph.D. dissertation entitled “Immune Modulation Response to Checkpoint Inhibition in Metastatic Melanoma” on December 1st. Erin was a student in the laboratory of Dr. Alan Tackett.
November publications
Toxicol Lett.
Drug Metab Dispos.
Identifying RNA Helicase Inhibitors Using Duplex Unwinding Assays.
Methods Mol Biol.
Urbaniak A, Piña-Oviedo S, Yuan Y, Huczyński A, Chambers TC.
European Journal of Pharmacology
Congratulations Dr. Koss!
Congratulations to Brian Koss who successfully defended his Ph.D. dissertation entitled “Epigenetic control of Cdkn2a.Arf protects tumor-infiltrating lymphocytes from exhaustion” on November 18th. Brian was a student in the laboratory of Dr. Alan Tackett and is now a post-doctoral fellow in the Center for Translational Pediatric Research as part of the Proteomics Technology Development Shared Resource under the direction of Dr. Rick Edmondson. A summary of his research is below.
T cell exhaustion in cancer is linked to poor clinical outcomes and evidence suggests T cell metabolic changes precede functional exhaustion. Direct competition between tumor-infiltrating lymphocytes (TILs) and cancer cells for metabolic resources often renders T cells dysfunctional. Here, we report an epigenetic mechanism contributing to the development of metabolic exhaustion in TILs. Environmental stress produces epigenome remodeling events within tumor-infiltrating lymphocytes resulting from loss of the histone methyltransferase EZH2. Using a multi-omics approach, we have defined an ARF-mediated, p53-independent mechanism by which EZH2 inhibition leads to mitochondrial dysfunction and the resultant exhaustion. Reprogramming T cells to express a gain-of-function EZH2 mutant resulted in an enhanced ability of T cells to inhibit tumor growth. Our data suggest manipulation of T cell EZH2 within the context of cellular therapies may yield lymphocytes which are able to withstand harsh tumor metabolic environments and collateral pharmacologic insults.
Grad School Informational Webinar
Thinking about graduate school in the biomedical sciences?
Join us on Thursday November 9, 2020 for a free online event where our current students will share their experiences in the UAMS Graduate Program in Interdisciplinary Sciences (GPIBS) Biochemistry Track.
Programmatic details & the application process will also be discussed.
Mary “Allie” Schleiff Student Highlight
Allie is a GPIBS Ph.D. student in the Biochemistry and Molecular Biology track. She is a fourth year student in the laboratory of Dr. Grover Paul Miller.
She graduated from Henderson State University in 2017 with an Honors Bachelor of Science degree in Biochemistry and a minor in Biology, and she received a regulatory sciences certification from the UAMS Department of Environmental and Occupational Health in Spring 2020.
Research Interest Statement
My research focuses on a subset of structurally similar non-steroidal anti-inflammatory drugs (NSAIDs) known as diphenylamine NSAIDs. Diphenylamine NSAIDs are taken more than 15 million times each year in the United States, but roughly 15% of all people administered diphenylamine NSAIDs have a clinically observable case of hepatotoxicity from the compounds. Previous studies identified that diphenylamine hepatotoxicity is dependent upon metabolic bioactivation and varied depending upon minor structural modifications to the diphenylamine structural scaffold, but little work exists to identify the specific mechanisms by which diphenylamines cause hepatotoxicity. I used computational tools to identify potential diphenylamine metabolic bioactivations in seven marketed or withdrawn diphenylamine drugs and experimentally validate these computational results. Thus far, I have discovered that diphenylamine NSAIDs are preferentially bioactivated into quinone-species metabolites in variable amounts and by a variety of cytochrome P450 enzymes dependent upon minor structural modifications to the diphenylamine scaffold. I hope that results from this work can help direct future development of diphenylamine-containing drugs in the future and help identify and stratify patients at-risk following diphenylamine NSAID dosage to promote more personalized patient care.
Something Notable About Time as a Graduate Student
I am so grateful that I was trained as a fresh graduate student by Dr. Dusty Barnette. I was always dropping things, breaking things, and having the same information repeated to me over and over again and Dusty never batted an eye, scolded me, or made me feel like a burden. Specifically, I’m appreciative to him for always getting the tall things off the high shelves for me!
Career Goals
My dream job would be in a contract research organization conducting preclinical and clinical studies for pharmaceutical clients. Once I obtain my PhD, I intend to take a post-doctoral position through the Center for Drug Evaluation and Research (CDER) to enhance my regulatory experience and make myself more marketable!
Experiment or Technique You Would Most Like to Do
Nuclear magnetic resonance is a major technique used frequently in regulatory science and in the pharmaceutical industry, but my only exposure to it was for a week or so as an undergraduate in my Analytical Chemistry course. I was overwhelmed and scared of it then and I still am, though I want to change that!
Fun Fact
Cleaning is legitimately one of my favorite hobbies, so most laboratories stress me out a bit – ha. If I wasn’t working in science, I would want to be a professional home organizer.
Publications
- Schleiff, M., Payakachat, S., Schleiff, B., Pinson, A., Flynn, N., Province, D., Boysen, G., Swamidass, S. J., Miller, G. P. “Significance of Multiple Bioactivation Pathways for Meclofenamate as Revealed through Modeling and Reaction Kinetics.”
- Publication – Accepted, Drug Metabolism and Disposition.
- Barnette, D., Schleiff, M., Datta, A., Flynn, N., Swamidass, S. J., Miller, G. P. “Meloxicam Methyl Group Determines Enzyme Specificity for Thiazole Bioactivation Compared to Sudoxicam.”
- Publication – Accepted, Toxicology Letters.
- Pinson, A., Pouncey, D., Schleiff, M., Fantegrossi, W., Prather, P., Radominska-Pandya, A., Boysen, G., Miller, G. P. “Significance of Competing Metabolic Pathways for Synthetic Cannabinoid 5F-APINACA as Revealed through Novel Reaction Kinetics.”
- Publication – Published, Molecules. DOI: 3390/molecules25204820
- Schleiff, M., Russell, L., Gonzalez, E., Bart, A., Broccatelli, F., Humphreys, G., Scott, E., Segall, M., Prasad, B., Hartman, J., Lauschke, V., Nwabufo, C., Takahashi, R., Durmus, S., Nichols, C., Martin, I., and Taub, M., Sodhi, J. “Advances in the Study of Drug Metabolism – Symposium Report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX).”
- Publication – May 2020, Drug Metabolism Reviews. DOI: 1080/03602532.2020.1765793
Grants
I am partially supported by a training grant through the Pharmacology, Toxicology, and Experimental Therapeutics Department in the UAMS Graduate School entitled, “Systems Pharmacology and Toxicology” (T32GM106999).
Awards
- 2020 Third Place Bhuvan Award for Excellence in Biochemistry Graduate Research – University of Arkansas for Medical Sciences Student Research Day
- 2020 Top 30 Finalist with Honorarium – Sternfels Prize in Drug Safety Discoveries
- 2020 Pfizer Society of Toxicology National Conference Student Travel Award – Society of Toxicology Computational Toxicology Specialty Section
- 2019 First Place Oral Presentation – University of Arkansas for Medical Sciences Graduate Student Association Research Symposium
- 2019 South Central Chapter Society of Toxicology Regional Conference Travel Award
- Graduate Student Achievement Award for Selection to the Drug Metabolism Reviews Editorial Board – University of Arkansas for Medical Sciences Fall Research Award Ceremony
- Graduate Student Achievement Award for Selection to the International Society for the Study of Xenobiotics New Investigator Group – University of Arkansas for Medical Sciences Fall Research Award Ceremony
- 2019 Outstanding Graduate Student Poster Presentation – Drug Discovery and Development Colloquium
- 2019 Invited Speaker with Honorarium – Drug Metabolism and Pharmacokinetics Symposium hosted by Genentech
- 2018 MC-Bios Computational Biology Conference Travel Award – Midsouth Computational Biology and Bioinformatics Society
Alicja Urbaniak appointed to JBMT editorial board
Congratulations to Dr. Alicja Urbaniak who has been appointed to the Editorial Advisory Board of the Journal of Biochemical and Molecular Toxicology (JBMT).