2018 Appointments

Caitlin CapertonCaitlin Caperton

B.A., University of Arkansas at Little Rock, 2015
Mentor: Aime Franco, Ph.D.

Research Project: Immune Microenvironment and Stromal Remodeling Associated with Follicular Thyroid Cancer

Thyroid cancer is one of the most rapidly increasing cancers in the US and is predicted to become the 4th most commonly diagnosed malignancy by 2030. Thyroid cancer and related pathologies are often associated with activating mutations in effectors of the MAPK pathway. These mutations are linked to changes in the tumor microenvironment, including migration of non-malignant cells and alternations in the extracellular matrix, that are believed to promote thyroid cancer and eventual progression to poorly differentiated disease. My project seeks to identify how Hras mutations associated with follicular thyroid carcinoma lead to changes in the tumor microenvironment and recruitment of immune cells that allow for tumor growth and progression. Later work will determine whether treatment with Mek or PI3K inhibitors can prevent the recruitment of the cells that we believe drive tumor development.

Melissa ClemensMelissa Clemens

B.S., University of Central Arkansas, 2004
MPH, University of Arkansas for Medical Sciences, 2016
Mentor: Mitchell McGill, Ph.D.

Research Project: Mechanisms and biomarkers of liver regeneration after APAP-induced hepatotoxicity.

Acetaminophen (APAP) overdose is the major cause of acute liver failure (ALF) and ALF-related deaths in the US.  The standard-of-care treatment for APAP hepatotoxicity is N-acetylcysteine (NAC).  However, NAC loses efficacy ≥16h after overdose and nearly half of all APAP overdose patients present later when the only option is liver transplant.  Interestingly, the liver has the ability to regenerate as much as 80% of its functional mass after injury and regeneration is critical for survival of ALF patients. Therefore, enhancement of regeneration is a promising treatment approach for APAP overdose patients. Unfortunately, the mechanisms of regeneration after APAP-induced hepatotoxicity are poorly understood.  Our lab recently demonstrated that the lipid phosphatidic acid (PA) is increased in the liver after APAP overdose and enhances regeneration signaling.  We further determined that the increased PA is due to suppression of lipin enzymes, which metabolize PA. Building on this knowledge, we plan to determine the mechanisms by which PA is regulated and promotes liver regeneration with hopes of identifying new drug targets.

Allie DavisAllie Davis

B.S., Henderson State University, 2017
Mentor: G. Paul Miller, Ph.D.

Research Project: Structure activity relationships in the bioactivation of halogen-containing drugs and its role in drug-induced hepatotoxicity.

The goal of this project will utilize both clinical data and experimental approaches to assess how inclusion of halogens in established drugs, investigational drugs, and new molecular entities affects metabolic generation of quinones and subsequent drug-induced liver injury (DILI).  Through a collaboration with the National Center for Toxicological Research, we have gained access to a comprehensive library of pharmaceutical and clinical data that reports prevalence and severity of adverse drug reactions.  We will use this information to identify halogenated compounds known to have varying degrees of DILI risk, halogenated compounds known not to cause DILI, and halogenated compounds whose risk of DILI is unknown.  We will conduct experiments to assess the relevance of quinone-producing pathways in vitro and compare our findings to reported clinical data to evaluate how quinone concentrations extrapolate to likelihood and severity of DILI.  Similarly, we will study pharmaceutical derivatives with different halogenated and nonhalogenated substituents to determine how steric, electronic, and chemical effects influence specificity and affinity of metabolizing enzymes and how those modifications direct bioactivation and detoxification pathways in the liver.  This information can be used to identify which families and classes of halogenated pharmaceuticals are most problematic to proper liver function and, in turn, contribute to minimization of DILI risk.

2017 Appointments

Lucas DeyoungLucas Deyoung

B.S., John Brown University, 2015
Mentor: Kevin Raney, Ph.D.

Research Project: DNA quadruplexes as inhibitors of Parp-1

G-quadruplexes are four stranded structures, which can occur in DNA and have been linked to stalled DNA replication, gross chromosomal rearrangements, regulation of transcription of proto-oncogenes, and many other cellular processes. These structures have been proposed as targets for anti-cancer treatments. My project will test the importance of G-quadruplex structures through modification of the genomic DNA sequence in cellular and mouse models.

Laura EwingLaura Ewing

B.S., University of Arkansas at Little Rock, 2005
M.S., University of Oklahoma, 2007
Mentor: Igor Koturbash, Ph.D. & Annie Lumen, Ph.D. (NCTR)

Research Project: Influence of dietary methionine an dradiation on normal tissue toxicity

The focus of my project is to investigate the modulatory effects of dietary methionine (Met) on health outcomes during radiotherapy (RT) through both animal experimentation and physiologically-based pharmacokinetic (PBPK) modeling. Met, like other methyl donors, can reverse the loss of DNA methylation induced by ionizing radiation (IR) and decrease its oxidative potential. Our preliminary data shows that higher Met intake, comparable to a Western diet, in combination with RT, results in altered gut physiology, reduced function of tight junction proteins, a shift in the intestinal microbiota from commensal to pathogenic flora, and decreased concentrations of Met and its metabolites in enterocytes. These results imply that, although Met is an essential amino acid, toxic effects are observed with Met overload that are exacerbated with exposure to IR. To investigate the changes in intestinal integrity, I will combine animal models of IR exposure and Met with physiologically-base pharmocokinetic modeling to track Met throughout the body. I will also analyze tissue samples from the mice to measure protein synthesis, including production of metabolites of Met, gene expression in intestinal epithelium, and DNA methylation after varying combination doses of IR and Met.

Brian KossBrian Koss

B.A., Hendrix College, 2008
Mentor: Alan Tackett, Ph.D.

Research Project: Eliminating effects of EZH2 inhibition on melanoma infiltrating lymphocytes

Unleashing antitumor lymphocytes through checkpoint inhibition and adoptive cell therapies are incredibly promising strategies to fight melanoma. It is known that the extreme conditions of the tumor environment greatly reduce the immune response and function of infiltrating cells. New approaches to combat the tumor suppression of an immune response in solid tumors are needed to overcome this barrier. The histone methyltransferase EZH2 (Enhancer of zeste homolog 2) has been shown to mediate survival signaling in tumors and hematopoietic cells, making them resistant to environmental stress. Small molecule inhibitors are currently in clinical trials for treatment of various malignancies. Combination of EZH2 inhibitors with immunotherapies are promising, but limited, due to the requirement for EZH2 in lymphocyte activation and function. The goal of my work is to use a systems biology approach to identify changes in lymphocyte survival pathways during EZH2 inhibition. The findings will be used to develop strategies to eliminate the off-target effects of EZH2 inhibition on lymphocytes in a model of mouse melanoma.

2016 Appointments

Dolapo AdejumobiDolapo Adejumobi

B.S., University of Arkansas at Little Rock; B.A., University of Arkansas at Little Rock, 2014
Mentor: Richard Kurten, Ph.D.

Research Project: Mucosal barrier function in human esophageal mucosa

Eosinophilic Esophagitis (EoE) is an inflammatory disease triggered by food antigens. It is thought that enhanced permeability of the esophageal mucosal barrier leads to submucosal penetration of food antigens and thereby contributes to disease pathogenesis. To evaluate this hypothesis, we are evaluating the permeability of human esophageal mucosa ex vivo using fluorescent tracers. We aim to identify disease relevant inflammatory mediators enhancing mucosal permeability and to understand the corresponding structural alterations in epithelial cell adhesion and tight junctions. We think that understanding how esophageal mucosal barrier function is suppressed in disease could contribute to the development of new therapeutic options for EoE patients. Supported by T32 GM106999

Brittney GarnerBrittney Garner

B.S., East Texas Baptist University, 2015
Mentor: Nancy Rusch, Ph.D.

Research Project: Ion channel abnormalities in lymphatic smooth muscle cells during experimental lymphedema.

Cancer-related lymphedema is an accumulation of fluid in the interstitial tissue that may result from radiation and/or surgery. Lymph vessels (LVs) play a vital role in maintaining fluid homeostasis by returning extracellular fluid from tissues back to the venous circulation. The distal-to-proximal flow of lymph fluid is accomplished by rhythmic contractions of LVs mediated by finely tuned Ca2+ signaling pathways in the lymphatic smooth muscle cells. Disruption or cessation of LV rhythmic contractions can result in excess fluid in the tissues, which is evident as lymphedema. Although it is known that L-type Ca2+ channels play an important role in LV contractions, the functions of other ioni channels in the lymphatic vasculature are poorly understood, especially during the pathological state of lymphedema. My research project will use an in vivo approach to characterize functional abnormalities of ion channels using a model of surgical lymphedema to help identify a potential therapeutic target to restore normal fluid homeostasis. Supported by T32 GM106999

Ryan MacLeodRyan MacLeod

B.S., University of Arkansas at Fayetteville, 2014
Mentor: Charles O’Brien, Ph.D.

Research Project: Develop a novel approach to suppress bone resorption through the inhibition of RANKL by utilizing the CRISPR-Cas9 system.

Osteoporosis is a pathological imbalance in the osteoclastic and osteoblastic remodeling of the skeletal trabeculae. It is caused by an increased stimulation of osteoclast formation and subsequent bone resorption by these excess osteoclasts. They cytokine responsible for stimulating osteoclast formation is receptor activator of nuclear factor kappa-B ligand (RANKL), and its increased expression in pathological bone loss has been demonstrated in the past. Existing osteoporosis therapies, such as bisphosphonates, have many adverse side effects. Therefore, new ways to suppress osteoclast formation are needed to improve patient care and the overall outcome of treatment.The goal of my project is to develop a novel approach to suppress bone resorption through the inhibition of RANKL by utilizing the CRISPR-Cas9 system. Once we determine the correct single guide RNA to utilize for the RANKL gene, we will develop a new transgenic mouse model that will express the sgRNA and the Cas9-KRAB selectively in osteocytes. The final stage of my project will be to determine fi the transgene blocks pathological bone resorption using an ovariectomy mouse model to simulate post-menopausal estrogen loss. Supported by the UAMS Translational Research Institute and College of Medicine

Samantha McClenahanSamantha McClenahan

B.A., Vassar College, 2013
Mentor: Mike Owens, Ph.D.

Research Project: To discover and test high affinity monoclonal antibodies against two toxic cathinones (MDPV/αPVP) for use in treating cathinone use disorders.

Synthetic cathinones are medically dangerous psychoactive drugs of abuse commonly known as bath salts. While their desired stimulant effects are in some ways similar to cocaine and amphetamines, synthetic cathinone abuse can lead to cardiovascular toxicity and severe adverse effects including hallucinations, psychosis, and suicidal actions. The goal of my research is to discover and test high affinity monoclonal antibodies against two toxic cathinones (MDPV/αPVP) for use in treating cathinone use disorders.Our studies are focused on evaluating the pharmacokinetics and cardiovascular effects of MDPV and the potential therapeutic use of anti-MDPV antibodies. Supported by T32 GM106999


2015 Appointments

Bill HyattBill Hyatt

B.A., Hendrix College, 2012
Mentor: William Fantegrossi, Ph.D.

Research Project: Abuse-related and persistent behavioral effects of synthetic cathinone 3,4-methylenediooxypyrovalerone and its enantiomers in rodents

In recent years, a surge of new designer drugs have become widely available in the US, and world, markets. Among those often found in the news is the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). MDPV has emerged as a deadly psychostimulant-like drug of abuse commonly found in commercial ‘bath salt’ preparations. We intend to determine the abuse-related behavioral profiles of racemic (RS), (R) and (S) isomers of MDPV, as well as investigate any persistent behavioral effects. Characterization of behavioral effects of MDPV, paired with pharmacokinetic and toxicity profiles, are crucial in establishing preclinical criteria for development and testing of novel therapy efficacy. Supported by the UAMS Translational Research Institute and College of Medicine.


Stephen ShrumStephen Shrum

B.A., Hendrix College, 2014
Co-Mentors: Lee Ann MacMillan-Crow, Ph.D./Nancy Rusch, Ph.D.

Research Project: Activating the mitochondrial calcium-activated large conductance potassium channel as a targeted therapy for reducing ischemia-reperfusion injury in renal transplantation

Donor kidneys having undergone cold storage and transplantation (CS/Tx) sustain ischemia-reperfusion (I/R) injury, leading to extensive morphological renal damage, impaired kidney function, mitochondrial damage, and ultimately less successful grafts. Activation of the mitochondrial isoform of the calcium-activated large conductance potassium (mBK) channel was recently shown to have a preconditioning cytoprotective role in I/R injury. However, the mBK channel is uncharacterized in the context of renal CS/Tx. Using an in-vivo rat model, my project investigates novel activity abnormalities of the mitochondrial calcium-activated large conductance potassium channel (mBK channel) that occur during cold storage and renal transplantation. The overarching goal of this project is to develop a mBK channel-targeted therapy for improving renal function following transplant. Supported by American Heart Association Predoctoral Fellowship Award

Julia TobacykJulia Tobacyk

B.S., Louisiana Tech University, 2014
Mentor: Lee Ann MacMillan-Crow, Ph.D.

Research Project: Implications of mitochondrial dynamics in renal cold storage following transplantation

Long-term graft viability continues to be problematic after transplantation, especially in kidneys that require cold storage (CS). Studies show that renal CS leads to increased mitochondrial injury in kidneys following transplantation. Mitochondria are dynamic organelles, which continually undergo morphological changes, including fission and fusion. In many diseased states, there is a clear imbalance in mitochondrial dynamics. The scientific premise of my project is to identify pathways involved in mitochondrial fission and fusion using in vitro and in vivo rat renal cold storage and transplant models. Supported by T32 GM106999

2014 Appointments

ChuckChuck Hay

B.S.S., Cornell College, 2010
M.S., University of Nebraska Medical Center, 2012
Co-Mentors: Eric C. Peterson, Ph.D./Michael Owens, Ph.D.

Research Project: Using adeno-associated viruses to express monoclonal antibody fragments to treat methamphetamine and amphetamine addictions

Methamphetamine (METH) abuse often leads to serious addiction, yet there are currently no FDA-approved treatments to treat this addiction. For my project, I will be using adeno-associated viruses (AAV) to induce long-term but transient expression of monoclonal antibody fragments (AAV-scFvs), which recognize METH and its active metabolite, amphetamine (AMP). We envision that these AAV-scFV will reduce or block physiological and behavioral effects of METH and AMP in rat models of acute and chronic METH abuse. Supported by T32 GM106999 (2014-2016).

Lascelles Lyn-CookLascelles Lyn-Cook

B.S., University of Arkansas at Little Rock, 2009
M.S., University of Arkansas for Medical Sciences, 2012
Co-Mentors: Alison Harrill, Ph.D./Philip Mayeux, Ph.D.

Research Project: Diversity outbred mice may improve preclinical screening for drug-induced liver injury (DILI)

Drug toxicity is the major adverse event leading to drug attrition during development and withdrawal from the marketplace. Unfortunately, liver toxicity is often difficult to predict with current preclinical models. One reason for poor prediction may be that conventional models lack genetic diversity. The Diversity Outbred (DO) mice comprise a genetically diverse population with genetic variability that is actually greater than the human population. We hypothesized that the DO mice, when used in preclinical drug screening, would accurately predict human relevant liver toxicities that conventional models missed. We have selected one drug –­ zileuton – for mechanistic assessment. We will perform metabolomics and transcriptomics analysis in the liver of sensitive and resistant DO mice to ascertain molecular changes that occur in susceptible individuals. Supported by T32 GM106999 (2014-2016)

Daniel MeekerDaniel Meeker

B.S., Harding University, 2012
Mentor: Mark Smeltzer, Ph.D.

Research Project: Developing a targeted nanotherapeutic approach to the treatment of biofilm-associated Staphylococcus aureus infections

The ability of Staphylococcus aureus to form a biofilm presents a serious clinical problem, often complicating treatment beyond the use of systemic antibiotics alone. This project focuses on the use of novel nanocages, the incorporation of antibiotics into the nanocages, and the conjugation of nanocages to antibodies specific to S. aureus. The goal is to develop a targeted therapy that allows for highly localized concentration of antibiotic and couples it with a photothermal effect of irradiated nanocages. Further, the potential toxicity of this nanotherapeutic approach will be evaluated to determine the therapeutic viability of our model. Supported by T32 GM106999 (2014-2015)

2013 Appointments

Alex AlundAlex Alund

B.S., University of New Haven 2012
Mentor: Martin Ronis, Ph.D.

Research Project: The role of NADPH oxidase 4 and oxidative stress in alcohol-induced bone loss

Chronic alcohol consumption and binge drinking are two major risk factors for osteoporosis and low bone mass. Alcohol-induced bone loss is driven by an increase in intracellular levels of reactive oxygen species (ROS) through induction of NADPH oxidases (NOX). We are specifically studying the role of NOX4, hypothesizing that it is at the head of a cascade that produces NOX-derived ROS as a result of alcohol metabolism in osteoblasts. Our studies are also looking at the potential of dietary antioxidants as a therapeutic intervention for alcohol-induced bone loss. Supported by T32 GM106999 (2013-2015)

Emily HolthoffEmily Holthoff

B.S., Ouachita Baptist University, 2011
Mentor: Steve Post, Ph.D.

Research Project: Perineural invasion as an indicator of clinical outcome in vulvar squamous cell carcinoma

Vulvar squamous cell carcinoma (vSCC) is a disfiguring malignancy of the female genital tract with a particularly high incidence in the state of Arkansas. We are investigating the role of perineural invasion as a potential indicator of tumor aggressiveness and prognosis for clinical pathologists confronted with cases of vSCC. We are also exploring the molecular interactions between tumor cells, nerve cells, and inflammatory infiltrates in these tumors to determine the mechanism by which perineural invasion occurs. Supported by the UAMS Translational Research Institute (2013-2014)

Clark SimsClark Sims

B.A., Hendrix College, 2012
Mentor: Philip Mayeux, Ph.D.

Research Project: Targeting renal perfusion and mitochondrial oxidants in a model of infant sepsis

Sepsis is the 8th leading cause of infant mortality in the U.S. and also is prevalent worldwide. Sepsis-induced acute kidney injury is a frequent complication of infant sepsis and increases the mortality rate from 25% to nearly 45%. Currently, there are no effective therapies to treat sepsis in infants and clinicians must rely only on supportive care usually initiated only after the presence of symptoms. Clark will be evaluating two new therapeutic targets in an animal model of pediatric sepsis. Clark was supported by T32 GM106999 (2013-2014) and is currently supported by an NRSA F31 award from NIDDK.