SPaT Faculty

I am a practicing nephrologist with a strong interest in acute kidney disease and have been using proteomic technologies for discovery and validation of biomarkers for over 15 years. We use targeted analysis of candidate markers by multiplexed bead array, ELISA and mass spectrometry and proteomic discovery analyses by liquid chromatography/mass spectrometry to identify and qualify biomarkers.

As a researcher, my primary interest is the effects of environmental toxins, such as lead and PCBs, on oxidative stress and the effects of mitochondrial dysfunction and oxidative stress on radiation-induced normal tissue damage. I am currently funded by NIEHS to assess the role of sirtuin 3 in regulating PCB-induced mitochondrial injury through AREA Grant mechanism, which is instrumental for exposing students to research.

My projects focus on links between glucose and insulin metabolism in processes leading to the development of Alzheimer’s disease. This age-related neurodegenerative disease is the most common cause of dementia and seems to depend on the accumulation of a peptide termed “amyloid-β.” Our studies utilize experiments conducted in cultured cells and models developed in mice, particularly mice genetically altered for amyloid-β along with diet-induced obesity. These studies may provide key insights into the cause(s) and treatment of both Alzheimer’s disease and perhaps even diabetes.

I am mostly interested in apoptotic endonucleases, the key enzymes regulating irreversible cell death after cell injury and during diseases. The nine known endonucleases seem to act by fragmenting DNA independently from each other. Our latest studies show the crosstalk between the endonucleases through several mechanisms. When necessary, tissues can protect themselves by inactivating endonucleases, while in other cases, the endonucleases activate each other and cooperate. By learning the mechanisms of this regulation, we hope to find universal cures of many human diseases including organ failures and cancers.

My focus is in vivo pharmacology of psychedelics and entactogens. We use a variety of rodent models to characterize the pharmacological effects of these compounds. We hope to understand the biobehavioral mechanisms by which these substances produce their therapeutic effects in clinical populations.

Research in my laboratory focuses on defining mechanisms of viral pathogenesis using mammalian orthoreovirus (reovirus) as a model system. Reoviruses are enteric pathogens that enter the bloodstream to disseminate to the central nervous system where they cause encephalitis. We work to define host and viral determinants that govern (i) the establishment of viral bloodstream infections and (ii) development of viral encephalitic disease.

Radiation-induced heart disease is a late occurring and sometimes severe side effect of radiotherapy of cancers in the thorax. To better understand how radiation causes heart disease, our lab uses preclinical in vivo models to study the effects of radiation on cardiac function, structure and molecular changes.

My interest is understanding the interplay between chemical exposure and nutritional or lifestyle habits, (diet selection and physical activity). We utilize small metabolomic biomarkers to characterize disease phenotypes.

My lab focuses on drug abuse during pregnancy and its effects on exposed offspring; specifically, we study neonatal opioid withdrawal syndrome (NOWS) following chronic opioid use in pregnancy. Our overall goal is to develop effective therapies for opioid use disorder during pregnancy that improve maternal-child health by diminishing NOWS severity.

My research is focused on the design and discovery of treatments for cancer and drug addiction, as well as aspects of prodrug and codrug design, drug metabolism studies, and the pharmacokinetic evaluation of potential clinical candidates.

Research in our laboratory focuses on the role of neuroinflammation in neurodegenerative disorders including Fetal Alcohol Spectrum Disorders (FASD) and Multiple Sclerosis (MS). Our work focuses on the mechanisms that regulate these disorders at the molecular and cellular levels, and in rodent models. Our overarching goal is to define novel therapies for FASD and MS.

My research focuses on the behavioral pharmacology of emerging drugs of abuse, including designer psychostimulants (“bath salts”), cannabinoids (“K2 / Spice” products), and hallucinogens. We employ a variety of in vivo assays to study drug actions, including biotelemetry, intravenous drug self-administration, conditioned place preference, drug discrimination, operant behavior, antinociception, and drug-elicited behaviors.

My research is centered around understanding how environmental exposures reprogram disease risk. My laboratory uses a multi-omics approach to understand how environmental chemicals dysregulate gene expression in normal tissues leading to various disease risk, including reproductive disorders and cancer. My laboratory has had a long-standing interest in studying the role of environmental and endocrine active agents including bisphenol A, phthalates, metal ions, and polycyclic aromatic hydrocarbons as disease causing toxicants and investigating their underlying epigenetic mechanisms.

I have clinical and translational research programs in acetaminophen toxicity that are funded by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). My research focuses on the development of biomarkers of acetaminophen toxicity using systems biology approaches involving genomics, metabolomics, and proteomics. I am also developing a new diagnostic assay for acetaminophen toxicity.

My research focuses on the use of brain imaging approaches to explore the impact of drugs of abuse and medications on human functional brain organization. Additionally, research in the BIRC also focuses on development of reliable and accurate biomarkers of risk, diagnosis, and treatment outcome for mental illness.

Research in my laboratory is focused on understanding the fundamental mechanisms T cells utilize to adapt to environmental stress. My laboratory is currently developing and applying cutting-edge proteomic approaches to elucidate how proteome turnover dynamics influence the ability of a T cell to persist in solid tumors. To translate these findings, my laboratory seeks to establish new immune monitoring methodologies and to engineer CAR T-cell therapies with superior persistence in the heterogeneous solid tumor environment.

The focus of my research interests is in understanding of the epigenetic effects and mechanisms of normal and cancerous tissue response to cancer therapy, and how the modification over the epigenetic profile may modulate tissue response to therapy. I have a broad background in molecular and radiation biology, with specific training in epigenetic mechanisms of response to radiation exposure in both in vitro and in vivo systems.

My research focus is in the field of hormone regulation of cancer and on the developmental origin of cancer risk and the impact of environmental estrogens/endocrine disruption on epigenetics reprogramming.

My lab has a long-term interest in oxidant generation and mitochondrial damage during renal ischemia/reperfusion as it relates to renal transplantation injury. In addition, the lab is examining the therapeutic potential of several agents to block mitochondrial and renal injury during warm and cold ischemia using animal models of ischemia, as well as sepsis.

My research focuses on using biomarkers of responses to toxicity and pathology across species to inform the use of modeling in vitro and in vivo systems for human safety assessment.

Our laboratory studies the fundamental mechanisms of liver injury and repair, particularly drug-induced liver injury. Our major goals are to identify and characterize 1) new drug targets to treat liver disease patients, 2) new biomarkers for prognosis in acute liver failure and 3) new methods for pre-clinical prediction of drug hepatotoxicity. We heavily rely on the murine model of acetaminophen overdose to accomplish those goals, though other models are also available in our laboratory. Additional interests include the pathophysiology of fatty liver diseases, and extrahepatic toxicity of acetaminophen.

The goals of my research are to assess and interpret the biological significance of metabolic activation and clearance of molecules especially in relation to pharmacological and toxicological effects on humans. In practice, my group leverages powerful analytical and biochemical tools to identify and quantitate small molecules including drugs, pollutants, and food additives as they undergo transformations through metabolic pathways and then correlate findings to biological activity and in vivo outcomes. Individual projects aim to (1) determine metabolic mechanisms and efficiencies for the activation and elimination of potentially toxic molecules, (2) phenotype enzymes responsible for metabolic pathways that account for variation in the population and confound the identification of toxicological mechanisms, (3) profile metabolites in humans and animal models to correlate in vitro findings to in vivo outcomes and potentially identify diagnostic biomarkers, and (4) develop computational models for metabolic activation and clearance of drugs contributing to adverse drug events to improve their safety for patients.

My research involves the detection and mechanisms of drugs of abuse, environmental toxicants, endogenous molecules and other xenobiotics. The analytical platforms developed are often used to support forensic, public health, and environmental laboratories.

The primary interest of my research has been focusing on the pathogenesis of hypertension in renal salt-reabsorption and the systemic vasculature. The long-term goal of our laboratory is to understand the mechanism of the development of hypertension and to translate our basic scientific discovery to clinics to contribute to a final cure for hypertension. Our most recent project is investigating the role and molecular mechanisms of immunity in stimulating salt/volume retention in the kidney, which contributes to the pathogenesis of salt-sensitive hypertension. We have acquired techniques and research experience involved in most areas of physiology, molecular biology, genetics, epigenetics, histology and vascular biology that are needed to pursue our goal of translational medicine.

Our research focuses on the cellular and molecular mechanisms that control bone remodeling and lead to osteoporosis. We have generated several novel genetically-modified mouse models. Trainees in my lab benefit from access to state-of-the-art techniques to modify the mouse genome and my experience in using these techniques to generate informative models of bone disease.

My laboratory is interested in investigating novel mechanisms by which cold storage induces injury in the kidney transplants leading to the identification of novel therapeutic targets that could lead to improved outcome after transplantation. Specifically, my laboratory is investigating the roles of proteasome, heat shock protein, and complement pathways during kidney transplantation. We have established a rat kidney transplantation model, which will be fundamental in studying mechanisms of kidney injury during transplantation, and applying therapeutics to improve outcome after transplantation.

My laboratory is focused on developing strategies to better direct skeletal tissue repair or prevent tissue degeneration. Currently we are pursuing two directions of research: one aimed at improving the intra-articular delivery of therapeutics within synovial joints to prevent osteoarthritis; the other at overcoming key bottlenecks to stimulating chondrogenesis within skeletal defects. At present, these projects use mouse, rat, and rabbit models of bone and joint injury to help address specific research goals.

The goal of our research is to understand the key role that macrophages play in the development and progression of chronic inflammatory diseases. In particular, our studies seek to provide mechanistic details regarding the ability of macrophage scavenger receptors to regulate the inflammatory response associated with cardiovascular disease and cancer.

My research interests involve understanding the neurobiological mechanisms underlying the addictive states produced by drugs of abuse. Specifically, I investigate the cellular and molecular mechanisms of signal transduction mediated by G-protein coupled receptors (GPCRs) with which drugs of abuse interact. I have recently shown that active phase I hydroxylated metabolites of synthetic cannabinoids present in K2/Spice may contribute to the rather unique toxicity profile associated with use of these drugs. As such, my laboratory provides students with the opportunity to employ cellular and molecular techniques to characterize the pharmacological and toxicological properties of novel drugs of abuse.

The overall goal of my research is to elucidate the cellular and molecular mechanisms responsible for skeletal aging. We employ genetically modified mouse models, pharmacological and cell culture approaches to unravel the molecular pathways that mediate the effects of sex steroid deficiency and old age on bone. Particular emphasis is given to the contribution of common aging mechanisms such as oxidative stress and cellular senescence.

My research interest is focused on learning the techniques and approaches for basic and translational cardiovascular/lymphatic pharmacology research. The primary focus is the mechanisms of damage to the lymphatic system during cancer chemotherapy and hypertension and to develop therapeutic strategies to reduce this damage. The laboratory uses techniques such as tissue microdissection, enzymatic cell isolation, flow cytometry, isolated vessel functional studies (ex: vessel contractility and calcium imaging), and gene and protein expression assays. The laboratory also employs surgical techniques to measure lymph flow in vivo using high-speed optical imaging.

My laboratory is interested in the enzymology and chemistry of nucleic acid enzymes. Helicases are enzymes that manipulate DNA and RNA in all aspects of nucleic acid metabolism. We are studying the mechanism(s) of helicases as well as protein-protein that govern activity. We have identified novel compounds that inhibit NS3 helicase from the Hepatitis C virus. In a separate project, we have discovered a signaling mechanism by which cells respond to DNA damage.

The goal of my laboratory is to discover abnormalities of ion channel expression and composition that contribute to systemic and pulmonary hypertension, and identify channel-based therapies to treat these diseases. We employ a multi-faceted approach of patch-clamp, molecular, cellular and in vivo techniques to accomplish this goal.

My research is on the detection, treatment, and pathogenesis of Staphylococcus aureus infection with a specific emphasis on infections involving bone and indwelling medical devices. I am the recipient of the New Investigator Award from the Orthopaedic Research Society and the Randall Award as the Outstanding Young Investigator from the South Central Branch of the American Society for Microbiology (ASM). I am currently an ASM Distinguished Lecturer and was recognized as the 2013 recipient of the UAMS Distinguished Faculty Scholar Award.

I am a practicing otolaryngologist with a primary interest in the treatment of vascular anomalies. My research focuses on how microRNAs drive abnormal endothelial cell growth in these lesions with the goals of targeting aberrant microRNA expression as a means of reducing the need for surgery or other invasive procedures, and of discovering novel microRNA biomarkers of vascular disease.

My research focuses on histone epigenetic mechanisms that regulate gene transcription and that are coupled to melanoma progression. We utilize a suite of techniques including proteomics of human biopsies, immunohistochemistry, cell culture, tumorigenicity assays, ChIPseq, biochemical and proteomic approaches for analyses of protein complexes, and cutting-edge mass spectrometry for the analysis of histone post-translational modifications. We also develop new technologies for epigenetic studies such as tools for detection of in vivo protein interactions and quantitative assays for histone-modifying proteins.

My primary research interest is to understand how endocrine status, diet and environment contribute to urological diseases encompassing prostate cancer, benign prostatic hyperplasia and lower urinary tract dysfunctions, with a focus on the role of physiological/dietary/environmental estrogens in uropathology.

My research focusses on high-throughput comparative genomics, developing tools to compare millions of genomes in a few seconds. We are developing methodologies where we can take a clinical isolate like blood or a fecal sample, and determine the microbial composition, including possible toxins and antibiotic resistance, in less than an hour. Our goal is to model microbial ecosystems within healthy and diseased people. Students in my group work both in the lab as well as using high performance computing for bioinformatic analysis.

Our lab focuses on the pathogenesis of cutaneous leishmaniasis. The goal of our lab is to define the factors that control both lesion development and resolution during infection caused by the protozoan parasite Leishmania. Specifically, we use a mouse model to manipulate the cells and pathways, such as VEGF-A/VEGFR2 signaling, that lead to the formation of new lymphatic vessels which promote disease resolution.