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Inflammation in the Alzheimer Disease Brain; Neuron-Specific Gene Transcription

Steven W. Barger, PhD
Departments of Geriatrics, Neurobiology & Developmental Sciences, and Internal Medicine
University of Arkansas for Medical Sciences

The Barger laboratory studies basic elements of cellular neurobiology, particularly as it relates to the development of Alzheimer's disease. Using cultures established from human and rodent brain tissue, Dr. Barger and coworkers examine the ways in which the Alzheimer amyloid protein influences the activation of events related to tissue inflammation. A separate but related project is analyzing the ways that genes are expressed by mechanisms unique to CNS neurons.

Pre-requisite courses:  No

Bioinformatics students:  Yes

Cell death endonucleases in tissue injury
Alexei G. Basnakian, MD, PhD
Departments of Internal Medicine, Division of Nephrology, University of Arkansas for Medical Science

Cell death is commonly associated with the enzymatic fragmentation of DNA. This includes a limited number of premortem DNA breaks (leading to cell death) and a huge number of postmortem DNA breaks (resulting from cell death). Cells have excessive DNA-degrading power provided by the recently recognized group of cell death DNases/endonucleases which includes: deoxyribonuclease I, deoxyribonuclease II, caspase-activated DNase, endonuclease G, DNase gamma and some other enzymes. Sometimes these enzymes are called “apoptotic endonucleases”, however they participate in necrosis as well. Other roles of cell death endonucleases include clean-up after cell death, removal of foreign DNA inside the cell, and cleavage of DNA circulating in plasma and other body fluids. Normally, host DNA is protected against these DNases. However, during cell injury or disease, genomic DNA becomes accessible to cell death endonucleases. Our group tries to identify endonucleases which participate in premortem DNA fragmentation in kidney tubular epithelium during ischemic or toxic acute renal failure, breast cancer or prostate cancer cells during drug-induced apoptosis. Our studies strongly indicate that the inhibition or inactivation of some endonucleases are protective against cell death in different models.
Pre-requisite courses: cell biology or molecular biology or biochemistry; or prior research experience
Bioinformatics students: Yes

Animal Models to Study Development and Aging in Multicellular Organisms
Helen Beneš, PhD
Departments of Neurobiology & Developmental Sciences, and Biochemistry & Molecular Biology
University of Arkansas for Medical Sciences

Three research projects in the Beneš laboratory currently utilize different animal models to understand development and aging in multicellular organisms: 1) sex-specific gene activity during mosquito development; 2) the role of glutathione S-transferases (GSTs) in preventing oxidative damage in muscle; and 3) the role of glutathione S-transferase S1 in the fruitfly, Drosophila melanogaster. More recently we have expanded a collaboration with the Zimniak laboratory at UAMS to examine the effects of lipid peroxidation in mammalian cardiotoxicity. We are using a Gsta4 null (“knock-out”) mouse to determine the role of electrophilic aldehydes, derived from lipid peroxidation, in signaling cell death in the heart. All projects involve techniques and approaches integrating biochemistry, molecular biology and genetics.
Pre-requisite courses: cell biology, general and organic chemistry
Bioinformatics students: Yes

Dynamics of regulation and function of diverse subsets of anterior pituitary cells.
Gwen V. Childs, PhD
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences

Classical studies of the anterior pituitary have shown 6 major cell types with unique neuropeptide releasing hormones as regulators from the brain. However, sensitive molecular assays show that pituitary cells are much more diverse than previously believed. Currently the funded projects in Childs laboratory focus on two examples of this diversity. The first study focuses on the significance and regulation of leptin by specific pituitary cells. Leptin is an appetite regulatory peptide normally produced by adipose cells. However, it might also be a cytokine in the pituitary, working locally to regulate pituitary cells. One project even looks at the possibility that it might be an endocrine factor, produced by gonadotropes to help regulate the reproductive system. The second study focuses on how pituitary cells integrate responses so that a cocktail of hormones is released to meet the needs of a particular physiologic state. Co-expression of multiple neuropeptide receptors is one of the ways the cells can meet these needs and this is regulated by gonadal steroids. The studies use molecular cytochemistry and cytophysiology with a focus on the analysis of individual cells.

Pre-requisite courses:  Cell biology

Bioinformatics students:  No

C. elegans as a model organism to study RNA interference (RNAi) as anti-viral defense mechanism.
Marie Chow, PhD & Khaled Machaca PhD
Departments of Microbiology and Physiology, University of Arkansas for Medical Sciences

This project is a collaboration between the Machaca and Chow laboratories. Although RNA interference (RNAi) has rapidly become a very experimentally useful tool to study gene expression and function, its true physiological functions are only just beginning to be understood. C. elegans offers a simple, genetically tractable organism to study mammalian viral infections and we have previously shown that C. elegans cells can be infected with a mammalian virus, Vesicular Stomatitis Virus (VSV). Using this system, we have recently shown that RNAi is an anti-viral defense mechanism in Caenorhabditis elegans. Infection of C. elegans cells with VSV is greatly enhanced in worm mutants that are RNAi deficient and reduced in worms displaying an enhanced RNAi phenotype. We are presently studying the molecular mechanisms mediating this anti-viral RNAi effect.
Pre-requisite courses: cell biology or molecular biology or biochemistry; or prior research experience
Bioinformatics students: Yes
 

Poliovirus entry into frog oocytes.
Marie Chow, PhD & Khaled Machaca PhD
Departments of Microbiology and Physiology, University of Arkansas for Medical Sciences

This project is a collaboration between the Machaca and Chow laboratories. Upon binding to a receptor on the surface of cells, viruses must be able to insert their viral genomes into the cytoplasm in order to initiate infection of a cell. We are using poliovirus (a mammalian virus) as a model virus to understand this entry mechanism, that is how the virus consistently and reproducibly is able to transport a highly negatively charged RNA genome across the hydrophobic lipid membrane of a cell. Last summer, a Brin summer student constructed an expression plasmid and showed that frog oocytes when microinjected with a RNA encoding the poliovirus receptor (PVR), successfully expressed PVR on the cell surface. We are presently asking whether poliovirus can infect these cells and whether specific cellular factors are required for successful infection.
Pre-requisite courses: cell biology or molecular biology or biochemistry; or prior research experience
Bioinformatics students: No

Regulation of β₂-Adrenergic Receptor Function in the Lung
Larry Cornett, PhD
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The Cornett laboratory studies regulation of β₂-adrenergic receptor gene expression in the lung. Adrenergic receptors mediate the effects of epinephrine and norepinephrine. We are interested in elucidating the molecular events involved in the regulation of β₂-adrenergic receptor gene expression by glucocorticoids, an action that is clinically useful in the treatment of asthma. We have identified a glucocorticoid response element (GRE) and have obtained evidence that other regulatory elements upstream of the promoter may play key roles in regulating β₂-adrenergic receptor gene transcription in airway epithelial cells. Ongoing projects include developing novel approaches to increasing β₂-adrenergic responsiveness in asthmatic airways and investigating intracellular trafficking of the β₂-adrenergic receptor following agonist exposure.

Pre-requisite courses: None

Bioinformatics students:  Yes

Reproductive Peptide Regulation of Bone and Cartilage Metabolism
Dana Gaddy, PhD
Departments of Physiology and Biophysics and Orthopedic Surgery
University of Arkansas for Medical Sciences

Research in the Gaddy laboratory focuses on reproductive peptide (Inhibin and Activin) regulation of bone and cartilage cell differentiation and bone metabolism. Signal transduction pathways of Inhibins and Activin are being studied. In addition, other projects include the mechanistic basis of the effects of microgravity and its countermeasures on the skeleton across age.

Pre-requisite courses: physiology or cell biology

Bioinformatics students:  Yes

The Reticular Activating System in Human Stress-Related Disease
Edgar Garcia-Rill, PhD

Department of Neurobiology and Developmental Sciences Director of Research, Arkansas Center for Neuroscience, University of Arkansas for Medical Sciences

The Garcia-Rill laboratory studies the function of the Reticular Activating System (RAS) of the brain in a number of different contexts. In field of central modulation of rhythms (such as sleep/wake and posture/locomoction), the laboratory focuses on functional aspects of the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, in particular in relation to etiologies of different disorders (schizophrenia, panic attacks, bipolar disorder, and depression). RAS output is measured by the evoked P50 potential, which may be moduated, by electroacupuncture (EA), a technique with potential clinical applications in disorders involving RAS output dysregulation. In another project, the Garcia-Rill laboratory is studying arousal and sensory gating in Alzheimer's disease, using monitoring of P50 potential amplitude. In collaboration with Dr. R. Skinner (UAMS), the laboratory is also studying locomotion and spinal cord circuits after spinal cord injury (SCI). Parallel animal and human studies should provide new understanding of the physiological changes occurring after SCI and on strategies that may modify spasticity, hyperreflexia, muscle atrophy, and locomotor performance in SCI patients. In collaboration with Dr. Anand (UAMS), the laboratory is also examining permanent brain stem and spinal cord circuitry changes following early exposure to repetitive pain or maternal separation, commonly found in premature babies. These studies examine physiology and behavior changes in both rats and humans. In conjunction with Dr. J. Dornhoffer, Dr. Garcia-Rill’s laboratory is monitoring pre-attentional and cognitive performance in association with motion sickness.

Pre-requisite courses: None

Bioinformatics students:  No

Clinical Research

Development of bioanalytical methodologies: Tools for the discovery of new medications.

Howard Hendrickson, PhD

Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences

The Hendrickson lab uses a variety of analytical tools to solve problems related to the quantitation of compounds in complex biological samples. We have particular interest in compounds that have shown promise in vitro and in animal models toward the treatment of diseases such as cancer and drug abuse. Due to the nature of our work, we are able to collaborate with several groups at UAMS. Currently we are investigating 1) the clinical relevance herbal-based medications with Dr. Bill Gurley and 2) the preclinical assessment of a novel chemotherapeutic agent for the treatment of cancer with Dr. Brendan Stack. LC-MS, GC-MS, and LC-EC are among the modern technologies at our disposal to solve complex analytical problems. We are also interested in developing secure databases for our clinical and preclinical studies.

Pre-requisite courses: Freshman Chemistry II

Bioinformatics students: Yes

Cellular and Molecular Mechanisms of Coupled Anion Transport
Michael L. Jennings, PhD
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The Jennings laboratory studies the structure, function, and regulation of ion transporters. Yeast (S. cerevisiae) and cultured human chondrocytic and osteoblastic cell lines are  currently used as experimental systems to study sulfate transporters that are involved in human genetic disorders.

Pre-requisite courses:  None

Bioinformatics students:  Yes

Regulation and Trafficking of b2-Adrenergic Receptors in Airway Cells
Stacie M. Jones, MD

Departments of Pediatrics, Physiology, and Biophysics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital

Laboratory interest is focused on mechanisms of b2-adrenergic receptor regulation and membrane trafficking in airway epithelium as it relates to therapeutic responsiveness in patients with asthma and respiratory disease. Additional emphasis is on the role of epidermal growth factor receptor in airway injury and repair.

Pre-requisite courses: None

Bioinformatics students:  No

Cellular and Molecular Mechanisms of Alcohol Toxicity in the Nervous System
Cynthia J. M. Kane, PhD
Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences

The Kane laboratory has made the new discovery that microglial cells are involved in the pathology of Fetal Alcohol Syndrome in the developing brain of a fetus exposed to alcohol during gestation. Using cell cultures and a rodent model of fetal alcohol exposure, the cellular and molecular mechanisms of alcohol toxicity in neurons and microglia are being identified. The goal of these studies is to design strategies to prevent alcohol damage to the developing fetus. Dr. Kane is not accepting students for the summer of 2008.

Pre-requisite courses: None

Bioinformatics students:  Yes

IEGF Receptors in Wound Healing
Richard C. Kurten, PhD
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The Kurten lab works to understand how EGF receptors are regulated during epithelial cell damage and the role the EGF receptor plays in the wound healing process. For these studies, bronchial and renal epithelial cells and several injury models are used. A major focus is to define the role vesicular trafficking plays in regulating receptor expression in lung and kidney injury.

Pre-requisite courses: Biochemistry, Cell Biology

Bioinformatics students:  Yes 

Ethanol-Induced Purkinje Cell Apoptosis in Neonatal Rats
Kim Edward Light, PhD

Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences

Current research interests involve the mechanism of ethanol-induced Purkinje cell death when delivered to rat pups during a specific vulnerable period shortly after birth. Ethanol is known to induce a concentration-dependent permanent loss of Purkinje cells; the Light laboratory has recently demonstrated that the cells die by apoptotic mechanisms. Current studies utilize confocal microscopy and image analysis with 3D reconstruction to identify and quantitate alterations in the morphological and phenotypical development of the Purkinje neurons subsequent to ethanol exposure during the vulnerable period.

Pre-requisite courses: None

Bioinformatics students: Yes

Cellular Mechanisms of Cell Survival and Death
S. Jesse Liu, PhD

Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences

Alterations in membrane transporters and metabolisms tilt the balance in cellular mechanisms for cell survival and for cell death during endogenous and exogenous stimuli (e.g., hormonal changes during aging and oxidative stress). Using multidisciplinary approaches and cultured cells, identification signaling pathways that could improve the survival of heart cells and those that could enhance specifically the death of cancer cells would enhance understandings of drug actions and drug development from natural products.
Prerequisites:  biology and chemistry

Bioinformatics:  Yes

Regulation of the Intracellular Membrane Trafficking
Vladimir Lupashin, PhD

Departments of Physiology and Biophysics, University of Arkansas for Medical Sciences

The Lupashin laboratory is interested in understanding the molecular mechanisms responsible for the generation and maintenance of intra-cellular membrane-bounded compartments. Specifically, we study the mechanisms and machinery that maintain the high degree of specificity inherent in transport vesicle docking in the secretory pathway. We are also interested in the mechanism of retention and retrieval of integral membrane proteins in different sub-compartments of the Golgi apparatus. We apply a wide range of biochemical, cell biological and genetic techniques to address these questions.

Pre-requisite courses: Biochemistry and/or Molecular Biology

Bioinformatics students:  Yes

Molecular Mechanisms Underlying Hormone Stimulation of Adrenocorticotropin Release

Marina V. Mikhailova, PhD

Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The overall goal of ongoing research project is determine the relative roles of the hypothalamic hormones arginine vasotocin and corticotrophin releasing hormone in causing signal transduction events and release of adrenocorticotropin (ACTH) from the anterior pituitary gland.  The experimental approaches used in laboratory include molecular cloning and expression of receptors in cell culture, and fluorescent resonance energy transfer (FRET) techniques to detect dimerization between G-protein coupled receptors.

Pre-requisite courses:  None

Bioinformatics students: No

Nitroanisole Detoxification by CYP2E1
Grover Paul Miller, PhD
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences

Nitroanisoles are environmental pollutants whose toxic potential depends on the efficiency of biological processes.  CYP2E1 likely plays an important role in nitroanisoles metabolism, but the efficiency of the process is unknown.  Kinetic profiling of CYP2E1 activity has been an important tool for assessing the activation and detoxification of many small molecular weight compounds.  Unlike traditional enzymes, CYP2E1 catalysis may involve multiple binding sites that alter the metabolism of compounds.  Recently, we explained unusual non-hyperbolic kinetics for 4-nitrophenol oxidation through the presence of an effector site, which when occupied, suppressed the reaction.  Lack of knowledge of this mechanism could lead to under- or over-estimations of the clearance of compounds from the body.  In the proposed project, we will test the hypothesis that the contribution of P450 enzyme, CYP2E1, to nitroanisole detoxification depends on the occupancy of an effector site by nitroanisoles or the corresponding metabolites.  Through a collaboration between UAMS and Ouachita Baptist University, we will: (1) determine the kinetic mechanisms for nitroanisole metabolism; (2) construct computer models for CYP2E1 complexes with substrates and effectors to predict non-hyperbolic reaction kinetics (Ouachita Baptist University), (3) identify binding site residues for monocyclic molecules through photoaffinity labeling; and (4) confirm functional role for effector site residues through site-directed mutagenesis.  Collectively, these findings will generate models to interpret and predict the efficiency of detoxification of nitroanisoles as well as provide tools for future toxicological studies.  In addition, the combination of biophysical and computational techniques provides an excellent opportunity to cross-train undergraduates and graduate students for successful careers in science. 

Development and modulation of neonatal and postnatal immune system by nutrients in infant formula
Shanmugam Nagarajan, PhD

Department of Microbiology and Immunology University of Arkansas for Medical Sciences, ACH Nutrition Center

Research in the Nagarajan’s laboratory is focused on understanding the molecular mechanisms of immune modulation by dietary factors.  Specifically, we are interested in studying how dietary factors prevent chronic inflammatory diseases such as breast and colon cancers, and atherosclerosis by affecting immune gene expression, and long-lasting effects on immune cells. In another related area, in utero and early post-natal exposure of nutrients present in infant formula on the neonatal immune development is studied, with emphasis on genes that help determine innate and adaptive immune response during fetal and postnatal development. This research utilizes rat and gene knockout mice models, and human inflammatory and endothelial and cancer cells.  In all these projects we employ a diverse array of immunological, biochemical, molecular, and cell biological techniques.  

Pre-requisite courses: Biology and Chemistry
Bioinformatics students: Yes
 

Functional Role of TRPC Channels in Astrocytic Response to Injury

Kevin D. Phelan, PhD

Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences

Astrocytes respond to injuries as diverse as ischemia, trauma and neurodegeneration through a common process called “activation”. The activation of astrocytes includes a well-described sequence of events including: hypertrophy, hyperplasia, migration to sites of injury, and the production and release of proinflammatory molecules such as nitric oxide, cytokines, and chemokines. Unfortunately, our understanding of the signal transduction pathways involved in regulating astrocytic activation is incomplete. The family of canonical transient receptor potential (TRPC) channel proteins channels represent a group of calcium-sensing channels that includes both store-operated and receptor-operated channels. Dr. Phelan’s laboratory is currently investigating the novel hypothesis that TRPC channels are key molecular players in the regulation of astrocytic activation. In vivo and in vitro activation protocols are being used to assess and compare the morphological and functional changes associated with astrocytic response to injury in wildtype and various TRPC family member knockout mice (e.g., TRPC1-/-, TRPC3-/- and TRPC6-/- mice). The results may provide the rationale basis for targeting TRPC channels in therapeutic treatments designed to alleviate neuronal dysfunction following CNS injury.
Pre-requisite courses: None

Bioinformatics students:  No

Transcription factor NF-kappa B in Immune senescence

Usha Ponnappan, PhD
Departments of Microbiology and Immunology and Geriatrics, University of Arkansas for Medical Sciences

Research studies in the Ponnappan laboratory are directed at understanding the biochemical and molecular mechanisms regulating transcription in Immune dysfunction, as it relates to human aging. Current focus of the research is directed at evaluating the role of the 26S proteasome, the non-lysosomal protease complex in the regulation of transcription factor NF kappa B mediated signaling in the immune system, including ubiquitination and deubiquitination processes in immune regulation.
Prerequisites: Chemistry and biology
Bioinformatics students: Yes

UGTs and Nuclear Receptor Activity in Biotransformation of Toxic Compounds
Anna Radominska-Pandya, PhD

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences

The Radominska-Pandya laboratory is investigating the mechanism of biotransformation of toxic compounds, including carcinogens, in humans and the involvement of drug detoxification enzymes and nuclear receptors in this process.  The ultimate goal of their studies is the identification and design of new drugs, nuclear receptors ligands and regulators of crucial cellular proteins and their application to the prevention of hepatic and intestinal diseases, including cancer.  Specifically they are working to: a) understand how UGTs are regulated on the gene level, b) define the substrate specificity and molecular mechanisms of drug metabolizing enzymes on the protein level,  c) identify and characterize direct interactions of UGTs and nuclear receptors (PXR, FXR, AhR) with their ligands, and d) develop and test new inhibitors and/or activators of the UGTs and nuclear receptors.  

Pre-requisite courses:  None

Bioinformatics students:  Yes

Mechanisms of Action of DNA and RNA Helicases
Kevin D. Raney, PhD
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences

The Raney laboratory is studying the mechanisms of action of DNA and RNA helicases in work that is funded by the National Institutes of Health. These enzymes manipulate DNA and RNA and enable replication of genomes. One enzyme being studied is from the Hepatitis C Virus, and is an important target for development of new drugs for treatment of liver diseases caused by this virus. Biochemical and molecular biological techniques are used to study the enzymes in vitro. 

Prerequisites: General chemistry, organic chemistry

Bioinformatics student: Yes

Genetic and metabolomic predictors of longevity and age-associated diseases.

Robert J. S. Reis, DPhil

Depts. of Geriatrics and Biochemistry & Molecular Biology at UAMS and the McClellan Veterans Medical Center (CAVHS), University of Arkansas for Medical Sciences

We have an NIH Program Project grant to quantitate metabolite levels and measures of metabolic activity and damage, as well as the status of antioxidant defenses.  We will use these to formulate robust predictors of future longevity in young adults, for a variety of model systems in which life span can be extended markedly by genetic or dietary means.  We will then seek common “fingerprints” indicative of future survival that may extrapolate to humans.  A database will be developed and a variety of means of data mining will be employed to interrogate it.  In the near future, we also plan to develop databases comprising a panel of measures (both those of known clinical prognostic value, and some of the novel markers developed in our model systems), monitored in healthy human subjects.  We can thus look for new markers that correlate well with established biomarkers, and evaluate the application of these metabolic profiles to predicting susceptibility to common diseases and conditions associated with reduced fitness (e.g., obesity, diabetes/impaired glucose tolerance, cancer, high blood pressure, and cardiovascular impairment). 

Pre-requisite courses: None.  Prior courses and/or experience with databases and/or data mining are desirable but not essential.

Bioinformatics students:  Yes

Cellular Mechanisms in Renal Failure
Robert Safirstein, MD.
College of Medicine, University of Arkansas for Medical Sciences

Research in the Safirstein laboratory focuses on the cellular mechanisms responsible for renal failure. The role of signal transduction and molecular pathways in the response to ischemic and nephrotoxin-induced acute and chronic renal failure are being explored. Of particular interest is the role of the mitogen activated protein kinases and their downstream targets as the lab has shown that these kinases are important to epithelial cell survival. Both animal studies as well as in vitro cell models of renal epithelial cell injury are used. Ultimately pathways of cell survival could be augmented to ameliorate the syndromes of acute and chronic renal failure. 

Pre-requisite courses: None

Bioinformatics students:  Yes

Molecular Biology of Gut Development and Colon Cancer
Frank A. Simmen, PhD
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, and the Arkansas Children’s Nutrition Center

There are three related research areas ongoing in the Simmen laboratory. In the first area, we are studying the molecular mechanisms by which the uterus and embryo communicate (embryo-maternal cross-talk). This involves studies of growth factors and transcription factors and their molecular mechanisms of action. In the second area of research, we are studying molecular aspects of gut development and are particularly interested in genes that help determine intestinal cell growth & phenotype and tissue morphogenesis during fetal and postnatal development. In the third area, we are studying how nutritional factors affect gene expression and with long-lasting effects on cell phenotype and pre-disposition to intestinal tumorigenesis. Experimental models and approaches used include experimental and large animal models, in vitro tissue and cell models, molecular and cell biology, and genomics.

Pre-requisite courses: None

Bioinformatics students:  Yes

Molecular Mechanisms of Uterine and Mammary Epithelial Cell Growth Regulation
Rosalia C. M. Simmen, PhD  
Department of Physiology and Biophysics
University of Arkansas for Medical Sciences, Arkansas Children's Nutrition Center

Studies in the Simmen’s laboratory are focused on two major research areas: 1) elucidation of the molecular mechanisms important for the control of uterine growth and differentiation and its implications on pregnancy and cancer; and 2) the biological consequences of nutrient/gene interactions that might underlie normal development of the mammary gland and initiation and progression of breast cancer in adult life. This research utilizes animal models (rat and mice) as well as human uterine endometrial and mammary carcinoma cell lines and employs a diverse array of molecular, physiological, and cell biological techniques.

Pre-requisite courses: Biology, Inorganic and Organic Chemistry

Bioinformatics students: No

Stress-Induced Alterations in the Brain and Activity-induced Alterations in the Spinal Cord After Spinal Cord Injury: Human and Animal Studies
Robert D. Skinner, PhD
Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences

The Skinner laboratory studies stress-induced alterations in the human brain using the P50 mid-latency auditory evoked potential to test reticular activating system (RAS) function in psychiatric diseases such as depression and Post Traumatic Stress Disorder (PTSD). The effects of antidepressant drugs such as SSRIs are being examined. In a second study, the mid-latency auditory evoked potential P13 (rat equivalent of the human P50) is used to identify the neurotransmitters and pathways important for RAS function.  A third project examines use-dependent alterations in spinal cord function following spinal cord injury (SCI) in humans.  This project, in conjunction with Dr. Kiser in the Dept. of Physical Medicine and Rehabilitation, uses passive bicycle-like exercise.  Similar studies of experimental SCI in animals are in progress. In both of these SCI studies changes in spinal cord circuitry are being measured.  These are good projects for engineering students to learn neuroscience.

Pre-requisite courses: None

Bioinformatics students:  Yes

Molecular Pathogenesis of Staphylococcus Aureus Musculoskeletal Infection
Mark S. Smeltzer, PhD
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences

Research in the Smeltzer laboratory focuses on Staphylococcus aureus as a musculoskeletal pathogen. We are particularly interested in the surface-exposed adhesions that allow S. aureus to efficiently colonize host tissues and indwelling medical devices. We are also interested in the regulatory events controlling expression of S. aureus virulence factors and, given its role in musculoskeletal disease, the nature of the adaptive response to growth within a biofilm.

Pre-requisite courses: Microbiology lab

Bioinformatics students:  Yes

Skeletal consequences of disease
Larry J. Suva, PhD

Departments of Orthopedic Surgery, Physiology and Biophysics
Director, Center for Orthopedic Research, University of Arkansas for Medical Sciences

The Suva laboratory is focused on understanding the cellular mechanism of the skeleton. Mechanisms involved in the stimulation of osteolysis in cancer (including breast and myeloma) as well as orthopaedic interventions are being investigated. In addition, we have extensive experience in the discovery and validation of protein biomarkers of bone diseases, including osteoporosis and osteoarthritis, as well as myeloma and metastatic breast cancer. The Center for Orthopaedic Research also has on-going research efforts utilizing 21^st century musculoskeletal imaging techniques, finite element analysis and mechanical testing.

Pre-requisite courses: None

Bioinformatics students:  Yes

Clinical and Bench Research

Mouse models of cardiovascular disease

Jerry Ware, PhD
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The Ware laboratory studies fundamental aspects of platelet biology to elucidate their role of in hemostasis, thrombosis and in the development of cardiovascular disease. Since platelets are anucleate fragments of cytoplasm, in vivo models are used based on the hypothesis that the unique cellular characteristics of megakaryocytes and platelets require the correct in vivo environment for meaningful assessment of biological properties. Currently, we are characterizing variants of the human glycoprotein Ib receptor expressed on the surface of circulating mouse platelets. Methodologies include the generation of transgenic and gene-targeted deletions in the mouse genome. These studies are defining the molecular mechanisms controlling normal platelet generation and the role of specific platelet receptors in disease.

Pre-requisite courses: None

Bioinformatics students:  Yes

Molecular Neurobiology - Regulation of Plp Gene Expression
Patricia Wight, PhD

Department of Physiology and Biophysics, University of Arkansas for Medical Sciences

The general interest of our laboratory is molecular neurobiology. Currently we are studying the regulation of the myelin proteolipid protein (Plp) gene, which encodes the most abundant protein found in CNS myelin. Through studies, utilizing both transgenic mice and deletion-transfection analysis, we have localized an important cis-acting element to a site within the 1st intron that we believe functions as an enhanceosome. We are in the process of characterizing the multiprotein complex that forms on this site to ultimately decipher the mechanism by which Plp gene expression is so potently activated in oligodendrocytes. Other projects in the laboratory are focused on the role that chromatin remodeling plays on oligodendrocyte differentiation.  NOTE:  Dr. Wight is not accepting students for the summer of 2008.

Prerequisites: None

Bioinformatics: Yes

Allosteric regulation of NMDA receptor function

Fang Zheng, PhD

Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences

The Zheng laboratory studies the allosteric regulation of N-methyl-D-aspartate receptors,  a subtype of glutamate receptors that is critical for learning and memory and neural development.  NMDA receptors are also implicated in many neurological diseases such as stroke and epilepsy, and psychiatric disorders such as schizophrenia.  A multidisciplinary approach that combines molecular biology, electrophysiology and structural modeling is used to investigate the interactions between allosteric regulators of the NMDA receptor function. 

Pre-requisite courses: None

Bioinformatics students:  Yes

Information for Mentors

Mentors at University of Arkansas, Fayetteville

Mentors at University of Arkansas at Little Rock