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SPaT Trainees

2016 Appointments

spat-dolapoDolapo 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

spat-ryanRyan 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

spat-samSamantha 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

 

spat-brittneyBrittney 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

2015 Appointments

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: Alison Harrill, Ph.D.

Research Project: The role of genetic background on adverse health effects due to prenatal exposure to environmental obesogen tributyltin

Tributyltin (TBT) is an environmental contaminant used widely in industrial processes and agriculture. TBT is used as a catalyst in the manufacture of glass coatings, plastics, and it is widely used as a biocide in paints for maritime use. A common source of human exposure to TBT is from drinking water owing to widespread groundwater contamination. Recent studies show that prenatal and early post-natal exposures to TBT may contribute to epigenetic reprogramming that promotes adipogenesis and hepatic steatosis at susceptible life stages. The goal is to determine strain-specific differences in bone and adipose tissue formation as well as liver effects in mice exposed prenatally to TBT. Further, we will explore the genetic alterations and gene expression induced by prenatal TBT exposure.  Supported by T32 GM106999

Bill Hyatt 1Bill 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.

2014 Appointments

ChuckChuck Hay

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

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).

LascellesLascelles Lyn-Cook

BS, University of Arkansas at Little Rock, 2009
MS, 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)

Meeker2014Daniel 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)

Clark Lab 2014Clark 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.

Emily SPaT 2014Emily Holthoff

BS, 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)