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.”
iBioDS Highlights
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 I used computational tools to identify potential diphenylamine metabolic bioactivations in seven marketed or withdrawn diphenylamine drugs and experimentally validate these computational results.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
Duah Alkam Student Highlight
Duah is a GPIBS Ph.D. student in the Biochemistry and Molecular Biology track. She is starting her 5th year in the laboratories of Dr. Mark Smeltzer and Dr. David Ussery.
She has a B.S. in Pharmaceutical Sciences and a M.S. in Pharmacology from The Hebrew University of Jerusalem.
Research Interest Statement
Osteomyelitis, or bone infection, is a devastating disease with limited treatment options. My dissertation explores the molecular pathways involved in the pathogenicity of the major cause of osteomyelitis, the bacterial agent Staphylococcus aureus. We draw on genome sequencing technologies coupled with comprehensive bioinformatic analyses to define the genetic landscape of the bacterium during in vivo osteomyelitis. These studies revealed strategies the bacterium employs to survive within the bone while fending off attacks by the host. Targeting these pathways may aid in the development of therapeutics to combat S. aureus infections.
Something Notable about Time as a Graduate Student
There is a pervasive positivity across the UAMS graduate school that I’ve been fortunate to experience through interactions that spanned three departments. My co-mentors exemplified this spirit through their collaboration and commitment to guiding me on topics ranging from the intricate details of Staphylococcus aureus biology to the value of comparative genomics. Equally crucial were the bioinformaticians on our team who taught me how to critically evaluate big data. These interactions have been the highlight of the past four years.
Career Goals
I plan to remain in the genomics/bioinformatics field.
Experiment or Technique You Would Most Like to Do
Anything involving genomic engineering, particularly with CRISPR/Cas9, is always fun.
Fun fact
My husband, Ziad, and I are on a quest to visit every major National Park in the United States – our favorite so far is the Grand Canyon.
Publications
Alkam D, Jenjaroenpun P, Wongsurawat T, Udaondo Z, Patumcharoenpol P, Robeson M, et al. Genomic characterization of mumps viruses from a large-scale mumps outbreak in Arkansas, 2016. Infect Genet Evol. 2019;75:103965
Alkam D, Wongsurawat T, Jenjaroenpun P, Connor S, Hobbs C, Wassenaar TM, et al. Three Complete Genome Sequences of Genotype G Mumps Virus from the 2016 Outbreak in Arkansas, USA. Genome Announc. 2017;5(32)
Brian Koss student highlight
Brian is a Ph.D. student starting his fifth year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Alan Tackett.
He has a B.A. in Biochemistry and Molecular Biology from Hendrix College.
Research Interest Statement
My doctoral work focuses on the dynamic interplay between the epigenetic and metabolic pathways used by T cells to sense and respond to environmental pressures. Specifically, I focused on the loss of the histone methyltransferase EZH2 (H3K27me3) in CD8+ T cells, which occurs during solid tumor infiltration and renders T cells dysfunctional. My work revealed loss of H3K27me3 leads to mitochondrial dysfunction and metabolic exhaustion, through a Cdkn2a.ARF-mediated, p53-independent mechanism. Reprogramming T cells to express a gain-of-function EZH2 mutant enhanced inhibition of tumor growth in a model of adoptive T cell therapy. My data suggest manipulation of EZH2 in T cells represents a potential strategy to protect tumor-specific T cells, which is currently unaccounted for in the clinical development of EZH2 inhibitors.
Career Goals
Once I am finished with my PhD, I plan to continue my current work and pursue early independence opportunities.
Experiment or Technique You Would Most Like to Do
This changes from time to time. However, I currently enjoy using proteomic approaches to interrogate protein turnover rates at a proteome level. I believe this approach will give us novel insights into how a cell prepares its proteome for rapid adaptation to environmental conditions.
Fun fact
My wife, Cary, and I have two boys, Bennett (5 years) and Parker (3 years).
Publications
- Koss, B.; Shields, B. D; Taylor, E. M.; Storey, A. J.; Byrum, S. D.; et. al. Epigenetic control of Cdkn2a.Arf protects tumor-infiltrating lymphocytes from metabolic-exhaustion. Cancer Research, (accepted).
- Trentzsch, M.; Nyamugenda, E.; Miles, T. K.; Griffin, H.; Russell, S.; Koss, B.; Cooney, K. A.; Phelan, K. D.; Tackett A. J., Iyer, S.; Boysen, G.; Baldini, G. Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum. Cell Death Discovery 6:8 (2020).
- Taylor, E.; Koss, B.; Davis L. E.; Tackett, A. J. Histone Modifications as Biomarkers for Immunotherapy. Methods in Molecular Biology 2055:213-228 (2019).
- Chiang, T.; Koss, B.; Su, L. J.; Washam, C. L.; Byrum, S. D.; Storey, A.; Tackett, A. J. Effect of sulforaphane and 5-aza-2’-deoxycytidine on melanoma cell growth. Medicines 6, 71 (2019).
- Lee, T.; Christov, P. P.; Shaw, S.; Tarr, J. C.; Zhao, B.; Veerasamy, N.; Jeon, K. O.; Mills, J. J.; Bian, Z.; Sensintaffar, J. L.; al. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. Journal of medicinal chemistry 62, 3971–3988 (2019).
- Shields, B. D.; Koss, B.; Taylor, E. M.; Storey, A. J.; West, K. L.; Byrum, S. D.; Mackintosh, S. G.; Edmondson, R.; Mahmoud, F.; Shalin, S. C.; Tackett, A. J. Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma. Cancer Research 79, 1113–1123 (2019).
- Ren, Z.; Ahn, J. H.; Liu, H.; Tsai, Y.-H.; Bhanu, N. V; Koss, B.; Allison, D. F.; Ma, A.; Storey, A. J.; Wang, P. PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation. Blood blood-2019000578 (2019).
- Shields, B. D.; Mahmoud, F.; Taylor, E. M.; Byrum, S. D.; Sengupta, D.; Koss, B.; Baldini, G.; Ransom, S.; Cline, K.; Mackintosh, S. G. Indicators of responsiveness to immune checkpoint inhibitors. Scientific Reports 7, 807 (2017).
- Lee, T.; Bian, Z.; Zhao, B.; Hogdal, L. J.; Sensintaffar, J. L.; Goodwin, C. M.; Belmar, J.; Shaw, S.; Tarr, J. C.; Veerasamy, N.; Matulis, S. M.; Koss, B.; Fischer, M. A.; Arnold, A. L.; Camper, D. V.; Browning, C. F.; Rossanese, O. W.; Budhraja, A.; Opferman, J.; Boise, L. H.; Savona, M. R.; Letai, A.; Olejniczak, E. T.; Fesik, S. W. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Letters 591, 240–251 (2017).
- Koss, B.; Ryan, J.; Budhraja, A.; Szarama, K.; Yang, X.; Bathina, M.; Cardone, M. H.; Nikolovska-Coleska, Z.; Letai, A.; Opferman, J. T. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget 7, (2016).
- Haverkamp, J. M.; Smith, A. M.; Weinlich, R.; Dillon, C. P.; Qualls, J. E.; Neale, G.; Koss, B.; Kim, Y.; Bronte, V.; Herold, M. J.; Green, D. R.; Opferman, J. T.; Murray, P. J. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity 41, 947–959 (2014).
- Koss, B.; Morrison, J.; Perciavalle, R. M.; Singh, H.; Rehg, J. E.; Williams, R. T.; Opferman, J. T. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 122, 1587–1598 (2013).
- Tripathi, P.; Koss, B.; Opferman, J. T.; Hildeman, D. A. Mcl-1 antagonizes Bax/Bak to promote effector CD4(+) and CD8(+) T-cell responses. Cell death and differentiation 20, 998–1007 (2013).
- Wang, X.; Bathina, M.; Lynch, J.; Koss, B.; Calabrese, C.; Frase, S.; Schuetz, J. D.; Rehg, J. E.; Opferman, J. T. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes and Development 27, 1351–1364 (2013).
- Cohen, N. A.; Stewart, M. L.; Gavathiotis, E.; Tepper, J. L.; Bruekner, S. R.; Koss, B.; Opferman, J. T.; Walensky, L. D. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chemistry and Biology 19, 1175–1186 (2012).
- Perciavalle, R. M.; Stewart, D. P.; Koss, B.; Lynch, J.; Milasta, S.; Bathina, M.; Temirov, J.; Cleland, M. M.; Pelletier, S.; Schuetz, J. D.; Youle, R. J.; Green, D. R.; Opferman, J. T. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature Cell Biology 14, 575–583 (2012).
- Stewart, D. P.; Koss, B.; Bathina, M.; Perciavalle, R. M.; Bisanz, K.; Opferman, J. T. Ubiquitin-independent degradation of antiapoptotic MCL-1. Molecular and cellular biology 30, 3099–3110 (2010).
Complete List of Published Work:
https://www.ncbi.nlm.nih.gov/myncbi/1pihpxbtPQJQh/bibliography/public/
Grants
- 2019-present NIH/NCI F31 predoctoral fellowship. Epigenetic regulation of metabolic stress pathways in melanoma infiltrating lymphocytes (F31CA232464). 7th percentile. $124,851
- 2019 Department of Defense Horizon Award. Epigenetic regulation of metabolic stress pathways in melanoma infiltrating lymphocytes. Recommended for funding as alternate.
- 2017-2018 Systems Pharmacology and Toxicology Graduate Fellowship, a T32 program; University of Arkansas for Medical Sciences.
Awards
- 2020 Sanofi Scholar-in-Training Award. American Association for Cancer Research (AACR), San Diego, CA
- 2020 Keystone Symposia Scholarship. Emerging Cellular Therapies: Cancer and Beyond. Banff, AB Canada
- 2019 Cancer Institute Member Spotlight. University of Arkansas for Medical Sciences, Little Rock AR.
- 2019 Graduate School Outstanding Achievement Award. University of Arkansas for Medical Sciences, Little Rock AR.
- 2018 Immuno-Oncology Innovation Award, Miltenyi Biotec. Fully paid travel to AACR 2018 and $2500 for research.
Dustyn Barnette Student Highlight
Dustyn is a Ph.D. Student in his 5th year in the Biochemistry and Molecular Biology Department. He joined the laboratory of Dr. Grover P. Miller for his research studies.
He has a B.S. in Biology from Ouachita Baptist University with minors in chemistry and art.
Research Interest Statement
A major obstacle in drug development is the occurrence of drug-induced liver injury (DILI). DILI can cause drugs to be rejected for market approval, or it can be idiosyncratic, meaning that it may not be discovered until after market approval.
The focus of my graduate research is to study metabolic activation of drugs to form toxic metabolites, which is one of the possible causes of idiosyncratic DILI. I am interested in the development and use of in vitro systems and computational models to serve as alternatives to in vivo trials for predicting and investigating mechanisms of drug induced hepatotoxicity. I have conducted thorough analyses of metabolic pathways of three marketed drugs (warfarin, terbinafine, and meloxicam) with special focus on pathways that contribute to bioactivation or detoxification. Through these efforts, I am working to establish the mechanisms that explain the idiosyncratic DILI observed for some drugs. The clinical application of this mechanistic knowledge is to be able to predict which patients will be vulnerable to DILI based on factors that affect metabolism such as genetics, environmental exposures, and drug-drug interactions.
Something Notable about Time as a Graduate Student
Last spring, I got to go to Baltimore to present my research at the annual Society of Toxicology meeting. Of course, the very first thing I did when I got there is take the metro train from the airport to the convention center. When the train got to my final stop, I walked over to the door ready to get off. I had no idea that this station was closed for construction, and the train was only stopping there because it had to wait on a crossing. No worries though, I found this all out very quickly after the train suddenly lurched ahead again, sending my unsuspecting self toppling like a flailing rag doll straight onto the lap of some random guy sitting next to the door. Sometimes, to only way to learn things is the hard way.
Career Goals
Once I get my Ph.D. I want to enroll in a post-doctoral position in a government research lab. Long term, I want my career to facilitate the development, improvement, and use of in vitro systems and computational models as alternatives to in vivo for predicting and investigating mechanisms of drug induced hepatotoxicity.
Experiment or Technique You Would Most Like to Do
I always enjoy when I get to use fluorescent compounds to chemically label the metabolites that I’m studying. There is something very fulfilling about working with brightly colored samples.
Fun fact
I like to hike. One of my favorite trails in Arkansas is the Lost Valley Trail near Ponca. At the hike’s end there’s a big cave with a waterfall in it, but my favorite part is actually around the halfway point. There’s a little cave located a couple hundred feet off the main trail that my cousins and I just stumbled upon by chance one time. You have to crawl to get into it, but once you’re in, you get to see dozens of little aquatic invertebrate fossils all over the walls and ceiling. It looks very cool!
Publications
Comprehensive kinetic and modeling analyses revealed CYP2C9 and 3A4 determine terbinafine metabolic clearance and bioactivation. Dustyn A. Barnette, Mary A. Davis, Noah Flynn, Anirudh S. Pidugu, S. Joshua Swamidass, and Grover P. Miller. Biochemical Pharmacology. October 9, 2019. doi: 10.1016/j.bcp.2019.113661, PMID: 31605674.
CYP2C19 and 3A4 dominate metabolic clearance and bioactivation of terbinafine based on computational and experimental approaches. Mary A. Davis, Dustyn A. Barnette, Noah R. Flynn, Anirudh S. Pidugu, S. Joshua Swamidass, Gunnar Boysen, Grover P. Miller. Chemical Research in Toxicolgoy. 2019 Apr 10. doi: 10.1021/acs.chemrestox.9b00006, PMID: 30925039.
Lamisil (terbinafine) toxicity: Determining pathways to bioactivation through computational and experimental approaches. Dustyn A. Barnette, Mary A. Davis, Na L. Dang, Anirudh S. Pidugu, Tyler Hughes, S. Joshua Swamidass, Gunnar Boysen, Grover P. Miller. Biochemical Pharmacology. August 2018, 156, 10-21. doi: https://doi.org/10.1016/j.bcp.2018.07.043, PMID: 30076845.
Stereospecific Metabolism of R- and S-Warfarin by Human Hepatic Cytosolic Reductases. Dustyn A. Barnette, Bryce P. Johnson, Dakota L. Pouncey, Robert Nshimiyimana, Linda Desrochers, Thomas E. Goodwin, Grover P. Miller. Drug Metabolism and Disposition. September 2017, 45 (9) 1000-1007. doi: https://doi.org/10.1124/dmd.117.075929, PMID: 28646078.
Exposure cessation during adulthood did not prevent immunotoxicity caused by developmental exposure to low-level trichloroethylene in drinking water. Kathleen M. Gilbert, Shasha Bai, Dustyn Barnette, and Sarah J. Blossom. Toxicological Sciences. March 2017, 157 (2): 429-437. doi:10.1093/toxsci/kfx061, PMID: 28369519.
Evaluation of virulence and antimicrobial resistance in Salmonella enterica serovar Enteritidis isolates from humans and chicken- and egg-associated sources. Jing Han, Kuppan Gokulan, Dustyn Barnette, Sangeeta Khare, Anthony W. Rooney, Joanna Deck, Rajesh Nayak, Rossina Stefanova, Mark E. Hart, and Steven L. Foley. Foodborne Pathogens and Disease. December 2013, 10 (12): 1008-1015. doi:10.1089/fpd.2013.1518, PMID: 24102082.
Awards
UAMS Graduate Student Association Research Symposium – Third Place for Poster Presentations (Fall 2019)
Arkansas Academy of Sciences Conference – Third Place for Biochemistry/Chemistry Oral Presentation (Spring 2016)
Graduate Student Explores Potential of Handheld DNA/RNA Sequencers in Outbreaks
By Amy Widner
Imagine there’s an outbreak of an infectious disease. Could health officials on the ground harness the power of new handheld DNA and RNA sequencers to monitor outbreaks in real-time and quickly contain them?
This question lies at the heart of research published in the journal Infection, Genetics and Evolution by UAMS Biochemistry and Molecular Biology track graduate student Duah Alkam. She and her advisers from the College of Medicine Department of Biomedical Informatics and the Department of Microbiology and Immunology collaborated with the Arkansas Department of Health to look at specimens collected during a 2016 mumps outbreak in Northwest Arkansas.
It took the Human Genome Project 13 years to complete the first sequence of a human genome in 2003. As sequencers became available for purchase, they were large, expensive and slow.
That has changed. Alkam used a device called the Oxford Nanopore Technologies MinION to sequence each sample in a matter of hours. To offload the data, she simply connected the MinION through a USB port to a laptop.
“You see results on your computer in real time,” Alkam said. “It’s fast, affordable and simple. The idea is that something like this might be useful during an outbreak, especially in a rural setting. If you can quickly identify a strain, you’re that much closer to understanding the origin of the outbreak, which may help contain it and protect the at-risk population.”
The new challenge for scientists is how to interpret the massive amount of data produced by these powerful sequencers. That is where the relatively new field of biomedical informatics comes in.
“Biomedical informatics allows us to look at genomes within a matter of hours and compare them, pinpointing connections and what might be important about these datasets,” Alkam said. “In this way, biomedical informatics is sort of the bridge between raw data and relevant information.”
In this case, Alkam was able to determine the unique characteristics of the specific variation of the mumps virus that was behind the 2016 outbreak. They used a computational technique called immunoinformatics to plot a “family tree” of sorts for the virus.
“We found that it was very similar to a strain that started an outbreak in Massachusetts around the same time in 2016, and it was also related to another strain that spread in Washington state, which may suggest that all three outbreaks originated from the same strain.”
While Alkam’s experiment was not conducted during an active outbreak, she and her advisers believe the results demonstrate great promise for the technique to be applied in the real world. Earlier in 2019, other scientists in the Department of Bioinformatics collaborated with researchers around the world for the first demonstration that the MinION could be used for the rapid genetic sequencing of multiple human viruses.
“The possibility of infectious disease outbreaks in health care settings and communities is something that unites us across the globe. We’re all vulnerable,” said Se-Ran Jun, Ph.D., Alkam’s adviser for the project and an assistant professor in biomedical informatics. “So at UAMS, it’s exciting each time we demonstrate how we can harness the power of new sequencing technology, big data science and analytics, and high performance computing in biomedical informatics to offer solutions.”
The project was funded with a grant to Jun from the UAMS for Translational Research Institute.
Alkam is a student in the UAMS Graduate School’s Graduate Program in Interdisciplinary Biomedical Sciences (GPIBS). Her other advisers are David Ussery, Ph.D., a professor in the Department of Biomedical Informatics; and Mark Smeltzer, Ph.D., a professor in the Department of Microbiology and Immunology.
Brian Koss Receives Prestigious NCI Fellowship
March 6, 2019 | A prestigious fellowship from the National Cancer Institute (NCI) will allow UAMS Graduate School student Brian Koss to advance his melanoma research.
The Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows (F31) will provide Koss with a three-year award of $124,851 to fund his research focusing on the protection of tumor-infiltrating immune cells in melanoma patients.
Koss, a third-year student in the UAMS Graduate Program in Interdisciplinary Biomedical Sciences, is now one of a select few scientists at UAMS ever to receive an F31 fellowship from the NCI.
“Becoming a National Cancer Institute-funded fellow has positioned Mr. Koss for immediate success during his graduate training, and also has primed him to become a nationally competitive cancer researcher in the future. These awards are highly competitive, so receiving this fellowship is a testament of Mr. Koss’s hard work, innovation and desire to help cancer patients in Arkansas and across our nation,” said Alan Tackett, Ph.D., associate director for basic research in the UAMS Winthrop P. Rockefeller Cancer Institute.
Koss is in his third year as a member of Tackett’s lab team at the UAMS Cancer Institute.
“Melanoma tumors apply many repressive factors on immune cells, which can prevent the success of standard immunotherapies,” Koss said.
Immunotherapy is a type of treatment that stimulates a person’s own immune system to recognize and destroy cancer cells. It has been found to be a very successful method of treatment for many, but not all, patients with melanoma, the deadliest form of skin cancer, and is now considered standard of care for the disease.
Koss’ research has revealed a method to protect immune cells in the harsh melanoma microenvironment which is known to prevent successful outcomes for some patients. His fellowship award will allow him to further define his findings and apply them to preclinical models of melanoma.
“This fellowship is impactful not only for Mr. Koss, but also for UAMS, as it highlights the innovative cancer research at the Winthrop P. Rockefeller Cancer Institute and supports our ongoing mission to become a National Cancer Institute-Designated Cancer Center,” Tackett said.