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College of Medicine: Department of Biochemistry and Molecular Biology

Student Highlights

Xiuqi Wang

Xiuqi Wang

I just started my sixth year in Biochemistry and Molecular Biology Ph.D. program and will graduate in October.

Education

China Pharmaceutical University, B.S. in Pharmacy (Basic Pharmacy).

Research

I have two research interests: 1) Discovery and optimization of novel inhibitors of clinically relevant targets 2) PROTAC and its applications. I have been working on multiple research projects within these research scopes.

I’m currently working on my dissertation thesis based on one of the projects, titled: Identification of Imidazo[1,2 a]pyridine pyridine derivatives as FLT3 kinase inhibitors for potential treatments of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematologic cancer characterized by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML, found in approximately 30% of newly diagnosed cases, most commonly consisting of internal tandem duplication (ITD) mutations in the juxtamembrane region. Recently, several FLT3 inhibitors have demonstrated clinical activity and three are currently approved – midostaurin, quizartinib, and gilteritinib. However, their clinical efficacies are limited in part due to the emergence of secondary clinical resistance, caused by multiple mechanism including on-target FLT3 secondary mutations – FLT3-ITD/D835Y and FLT3-ITD/F691L being the most common, as well as the off-target activation of alternative pathways including the BCR-ABL pathway. Therefore, in order to overcome drug resistance and further improve outcomes, new compounds targeting FLT3-ITD with secondary mutants are urgently needed. In my works, three compounds were identified with potent anti-leukemic effects, and may be further developed for treatment of AML.

Notable about his time as a Graduate

Throughout my Ph.D. periods, I got to know that research is never a solitary work. It requires frequent communication and close collaboration to get the work done.

Career Goals

I will seek postdoc training after my Ph.D. I have already accepted the postdoc offer at Dana-Farber Cancer Institute, Harvard Medical School, working with Dr. Jun Qi. My vision for my future career is to take on the academic path and be an independent principal investigator after the postdoc training.  

Experiment or technique you would most like to do (could be something you enjoy doing or something you have never done but would like to get the opportunity to do)

I like the design and synthesis of new compounds because there is a sense of satisfaction in creating something new.

Fun Fact about Xiuqi

I like hiking and exploring nature.

Katherine “Katie” Bronson

Katie Bronson

Katie is a fifth year student in the Biochemistry and Molecular Biology Ph.D program.

She attended Liberty University where she completed a Bachelor of Science degree in biology with a minor in chemistry

Research Interest

My research focus is on the conserved RNA-binding protein Musashi, the proteins it associates with, and the effect those associations have on regulating translation. Musashi is a biomarker for stem cells, regulating asymmetrical differentiation and maintaining a stem cell population. Originally studied as a translational repressor, the MacNicol lab has found that Musashi is required for the translational activation of specific transcripts. However, while Musashi uses its two N-terminal RNA-recognition motifs to bind to RNA, its C-terminus is disordered and contains no enzymatic or catalytic domains. Therefore, Musashi must require protein interactions in complexes to regulate translation, the composition of which could regulate Musashi-dependent translational effects. One of those proteins is Lsm14B. We are one of the first labs to identify Lsm14B as a translational activator, and the first group to identify the Musashi:Lsm14B interaction to be necessary to translate Mos and Cyclin B5 proteins in Xenopus oocytes to re-initiation of the cell cycle as well as translating the pituitary development-specific transcription factor Prop1. I have also discovered over 200 proteins that likely associate with Musashi independent of RNA in the mouse anterior pituitary through immunoprecipitations and mass spectrometry. My research will lay the groundwork for future investigations into the regulation of Musashi-bound RNA transcripts due to Musashi-protein interactions.

Notable about her time as a graduate student

Being a Ph.D. student is already a unique experience – a global pandemic in the middle of your Ph.D. truly makes it even more unique. The amount of personal growth I have experienced not only through the usual Ph.D. experience but also through these universally trying times has affected my approach to science and my research goals, highlighting the need for good science and excellent communication.

Her career goals

I will be expanding my research training and experience through a post-doctoral research position here at UAMS.

Experiment or technique she would most like to do

I would love to learn how to conduct bioinformatics analyses.

Fun fact about Katie

I joke that I’m preparing my retirement hobbies – I love gardening, crochet, reading, and tennis. A goal of mine is to have a library of books I’ve already read.

Mason McCrury awarded NSF-GRFP

Mason McCrury and Samantha Kendrick
Mason McCrury and Samantha Kendrick, Ph.D.

Congratulations to Mason McCrury, a Ph.D. student in the lab of Dr. Samantha Kendrick, for receiving a NSF-GRFP. The Graduate Research Fellowship Program supports outstanding graduate students who have demonstrated the potential to be high achieving scientists and engineers. Mason’s project is entitled “Investigating DNA Secondary Structure Formation and Mutagenesis.”

Lauren Clai Morehead

women in a mustard yellow with white daisy shirt smiling
Clai Morehead

Clai is a 6th year MD/Ph.D student in her 4th year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Alan Tackett and Dr. Isabelle Racine Miousse

She has a BS in Chemistry from Southern Arkansas University

Research Interest Statement

Immune checkpoint inhibitor therapy has drastically improved outcomes in treating cancer, particularly in melanoma. However, half of melanoma patients are resistant to treatment. One mechanism used by tumor cells to evade immune attack is to down-regulate major histocompatibility complex (MHC) class I molecules, which are required for cytotoxic CD8+ T-cells to eliminate cancer cells. To increase immunotherapeutic efficacy, it is critical to identify how to restore MHC-I expression on cancer cells so that tumor antigens are presented. We found that resveratrol elevated MHC-I expression, thereby improving CD8+ T-cell killing. Through proteomic interrogation, we identified the STING pathway as a potential mechanism of action. Further studies indicated that resveratrol-mediated STING signaling induced MHC-I expression through both interferon-independent and dependent pathways. Our results have uncovered the ability of STING to induce MHC-I expression independent of interferon signaling, broadening the potential of STING activation as a tool to improve immune checkpoint blockade.

Something Notable about Time as a Graduate Student

On my desk I have two quotes, one is from Joan Didion from The Year of Magical Thinking (“Read, learn, work it up, go to the literature. Information is control) and the other is from Merlin Sheldrake from Entangled Life (“What’s astonishing is the gulf between what we expect to find and what we find when we actually look”). Over the course of my studies, I’ve learned that being a scientist is an interplay between empowering yourself to ask good questions through information and expecting that the answers could be far away from what you imagined. I’m taking Didion’s quote a bit out of context for my purposes, but I relate to it in context as well.

Career Goals

As an MD/PhD student, my immediate tasks proceeding my PhD are returning to medical school to finish my medical education and then moving on to medical residency. My goal is to match into a dermatology residency program. I would like to continue contributing to research throughout the rest of my medical training. Post-residency, I plan on seeking an academic position and splitting my time between clinic and research. I would like to focus on inflammatory skin diseases and clarify targetable pathways for treatment. Health equity is also important to me. Currently I’m reading Health Communism by Artie Vierkant and Beatrice Adler-Bolton, and it really forces me to reconcile to the negative social processes that my fields help enable. When I become a physician-scientist, using my insight on both fields and how they serve as a source of knowledge and beneficence but also of capital, I plan on being involved in work progressing social justice initiatives to reach better health for all.

Experiment or Technique You would Most Like to Do

Honestly, I’m less interested in the performance of the experiments themselves, I’m more so into developing questions and plans to answer them. So, I’d like to do whatever answers the question.

Fun Fact

I like kpop; I can list all 22 members of NCT in age-order! I implore you to listen to “Sticker” by NCT 127.

Publications

The evolving clinical landscape for dendritic cell vaccines and cancer immunotherapy MJ Cannon, MS Block, LC Morehead, KL Knutson Immunotherapy 11 (2), 75-79

Further clinical advancement of dendritic cell vaccination against ovarian cancer LC Morehead, MJ Cannon Annals of research hospitals 2

Differences in cell death in methionine versus cysteine depletion KF Wallis, LC Morehead, JT Bird, SD Byrum, IR Miousse Environmental and molecular mutagenesis 62 (3), 216-226

Awards

Best Talk – 35th National MD/PhD Conference Diversity Award – 35th and 37th National MD/PhD Conference Melanoma Research Foundational Medical Student Award

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].

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.”

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

  1. 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.
  2. 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.
  3. 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
  4. 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

  1. 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).
  2. 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).
  3. Taylor, E.; Koss, B.; Davis L. E.; Tackett, A. J. Histone Modifications as Biomarkers for Immunotherapy. Methods in Molecular Biology 2055:213-228 (2019).
  4. 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).
  5. 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).
  6. 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).
  7. 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).
  8. 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).
  9. 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). 
  10. 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).
  11. 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).
  12. 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).
  13. 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).
  14. 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).
  15. 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).
  16. 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).
  17. 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.

Megan Reed Student Highlight

Megan is a Ph.D. student in her 5th year in the Biochemistry and Molecular Biology Department. She joined the laboratory of Dr. Robert Eoff for her research studies.

She has a B.S. in Biology with a dual minor in Chemistry and Psychology from Henderson State University.

Research Interest Statement

My project involves elucidating various mechanisms that glioblastoma brain tumors use to tolerate, repair and ultimately survive chemotherapeutic intervention. We are most interested in investigating the alternate functions of the DNA damage tolerance polymerase kappa (hpol k) and how these responses aid in tumor survival. Overexpression of this polymerase has been linked to tumor recurrence and resistance to standard-of-care chemotherapeutics. Understanding the possible ways that hpol k promotes these outcomes could help develop more effective treatments for glioblastoma patients.

Something Notable about Time as a Graduate Student

A fun fact about the Eoff lab is we are all left handed. We have this running joke that a requirement to join the lab is you must be left handed.

In all seriousness though I would say I have really enjoyed being part of the Biochemistry Department. I have built life-long friendships and have received tremendous support not only from my primary advisor but from many of the labs in this department. I like to joke that I am the department’s graduate student as I have pretty much gone to every lab at one time or another asking for experimental advice or to borrow reagents. My graduate school experience wouldn’t have been as successful if it was not for the faculty, postdocs and students that make up the Biochemistry Department.

Career Goals

Once I am finished with my PhD, I plan to pursue post-doctoral research in a lab focused on developing 3D tumor model systems. My long term goal is to conduct research using these model systems to help predict patient drug response, thereby opening up access to personalized chemotherapeutic treatments that are currently unavailable to most cancer patients.

Experiment or Technique You Would Most Like to Do

I really enjoy immunofluorescence microscopy. I don’t think I will ever get tired of taking beautifully colored fluorescent images.

Fun fact

I enjoy spending time with family, friends and hiking with my dog Brain.

Publications

Bostian, A. C., Maddukuri, L. M., Reed, M. R., Savenka, T., Hartman, J. H., Davis, L., Pouncey, D.L., Miller, G.P., and Eoff, R. L. Kynurenine signaling increases DNA polymerase kappa and promotes genomic instability in glioblastoma cells. Chem. Res. Toxicol. 2016, 29(1): 101-8.

Byrd, A. K., Zybailov, B. L., Maddukuri, L., GAO, J., Marecki, J. C., Jaiswal, M., Bell, M. R., Griffin, W.C., Reed, M. R., Chib, S., Mackintosh, S. G., MacNicol, A. M., Baldini, G., Eoff, R. L., and Raney, K. D. Evidence that G-quadruplex DNA accumulates in the cytoplasm and participates in stress granule assembly in response to oxidative stress. J. Biol. Chem. 2016, 24(3): 432-36.

Zafar, M. K., Maddukuri, L., Ketkar, A., Penthala, N.R., Reed, M. R., Eddy, S., Crooks, P. A., and Eoff, R. L. A small-molecule inhibitor of human DNA polymerase h potentiates the effects of cisplatin in tumor cells. Biochemistry. 2018, 57(7): 1262-73.

West, K. L., Kelliher, J. L., Xu, Z., An, L., Reed, M. R., Eoff, R. L., Wang, J., Huen, M. S. Y., and Leung, J. W. C.  LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic Acids Res. 2019, 47(12): 6236-6249.

Ketkar, A., Maddukuri, L., Penthala, N. R., Reed, M. R., Zafar, M. K., Crooks, P. A., and Eoff, R. L. Inhibition of human DNA polymerases eta and kappa by indole-derived molecules occurs through distinct mechanisms. ACS Chem Biol. 2019, 14(6): 1337-1351.

Reed, M. R., Maddukuri, L., Ketkar, A., Byrum, S. D., Zafar, M. K., Bostian, A. C. L., Tackett, A. J., and Eoff, R. L. Inhibition of tryptophan-2,3-deoxygenate impairs DNA damage tolerance and repair in glioma cells. (In preparation)

Patents

U.S. Provisional Patent Application No.: 62/792,226

Title: Naphthoyl, napthalenylmethyl, and naphthalenysulfonyl indole aminoguanidine analogs as DNA polymerase kappa inhibitors targeting glioblastoma.

Inventors: Robert L. Eoff, Peter Crooks, Narsimha Penthala, Amit Ketkar, Leena Maddukuri, and Megan Reed

BV Reference No.: 2019-09

Awards

2017: First place overall, for poster presentation at UAMS Student Research Day

2017: First place, Bhuvan award for excellence in biochemistry

2020: First place overall, for poster presentation at UAMS Student Research Day

2020: Second place, Bhuvan award for excellence in biochemistry