Virginia Commonwealth University Academics
 

FACULTY RESEARCH and PROJECT DESCRIPTIONS (in alphabetic order)

Suzanne E. Barbour, Ph.D.

Research Description: Regulation of cell phospholipid metabolism by phospholipase A2, lipid metabolism in resting and activated macrophages.

Undergraduate Projects: To be Determined


Harry D. Bear, M.D., Ph.D. Research Description: Cancer immunology and immunotherapy, and T lymphocyte biology

Undergraduate Projects: To be Determined


Patrick M. Beardsley, Ph.D. Research description: The pharmacology (preclinical) of the drugs of abuse.

Undergraduate Projects: To Be Determined

W.C. Broaddus, M.D., Ph.D.

Research Description: Molecular biology of and gene-based therapies for brain tumors.

Undergraduate Projects: To be Determined


Francine Cabral, Ph.D. Research Description:  Free-living amoebae as agents of human disease

Undergraduate Projects: To be Determined


Guy Cabral, Ph.D. Research Description: Molecular biology of viruses

Undergraduate Projects: To be Determined


Gail E. Christie, Ph.D. Research Description: My laboratory studies protein:nucleic acid interactions involved in the regulation of prokaryotic gene expression. Our primary focus is elucidation of the mechanism of action of a phage-encoded transcription factor; other projects characterizing different phage and bacterial regulatory sequences/loci are also underway.

Undergraduate Projects: Research opportunities for undergraduates might involve isolation and characterization of phage or bacterial mutants via classical microbial genetics or site-directed mutagenesis; subcloning and subsequent analysis of regulatory elements using plasmid expression vectors; in vitro studies of interactions between purified proteins and DNA; DNA sequence analysis; construction of protein overexpression plasmids, etc.


Severn B. Churn, Ph.D. Research Description: My research is directed at characterizing neuronal second messenger systems that are altered in pathologies such as seizure and stroke. The focus of my laboratory is to characterize the effect of seizure activity on the activity of a calcium-regulated, neuronal enzyme-CaM kinase II. In addition, we are also investigating how modulation of CaM kinase II activity results in altered neuronal function.

Undergraduate Projects: Potential projects for undergraduate students would include immunohistochemical studies to determine the effect of stroke and seizure activity on CaM kinase II and neurotransmitter receptors. Techniques utilized for these studies include SDS-PAGE, western analysis and immunoreactivity assays. We are also investigating how second messenger systems modulate neurotransmitter receptor function. This includes receptor binding assays, phosphorylation reactions and the use of radioisotopes. Additional projects can be discussed with individual students.


Shijian Chu, M.D., Ph.D. Research Description: My research interests are in signal transduction and gene regulation in the respiratory system. My current work involves two clinical situations where significant changes in gene expression occur. One of the situations is lung injury where I am focusing on a cytokine, TNF-alpha.   TNF-alpha is a well-documented systemic proinflammatory factor. In acute lung injury, TNF-alpha plays a pivotal role in both inflammatory and protective responses in microvascular endothelia. The questions I ask in this project include how signals are relayed from TNF-alpha to target genes; under which conditions inflammatory responses are initiated and under which conditions protective responses are activated; and what genes are regulated by TNF-alpha in microvascular endothelia. The second situation is lung fluid clearance at birth. Many transport molecules (such as channels) in respiratory epithelium are actively regulated at birth to accomplish the transition of the lung from a fluid-filled fetal organ to air-filled adult lung ready for air breathing. Failure or delay of lung fluid clearance would cause infantile respiratory distress syndrome or transient tachypnea of the newborn. At birth, some of the transport molecules are up regulated while others are down regulated. In this project, I am interested in the signals that initiate perinatal gene regulation and protein factors that regulate genes in opposite directions. All these studies address a fundamental question as how genes are regulated in response to physiological and pathological signals. These regulations may enhance cell survival however they may also result in cell damages. I hope these studies will eventually lead to strategies that will enable us to manipulate the clinical process in these situations.

Undergraduate Projects: Short-term student research will be available in one of our signal transduction projects. Project details will be discussed with the students. It will depend on the time available and the interests of the students. You will be able to learn a variety of research techniques such as cloning, gene expression, cell culture, and immunohistochemistry. There is a group of students working at the VA Medical Center. Parking is always free.

Paul Dent, Ph.D. Research Description: The research centers around "Signaling by the EGF Receptor/MAP Kinase Pathway: a Protective Response to Multiple Stresses in Normal and Tumor Cells."
Undergraduate Projects: Student research is available in one of our signal transduction projects. Project details will be discussed with the students. It will depend on the time available and the interests of the students.

William Dewey, Ph.D.
Department of Pharmacology and Toxicology
100 McGuire Hall
827-0501
wdewey@vcu.edu
 
Research Interests-
The research carried out in this laboratory is directed toward elucidating the mechanism of action of drugs of abuse with emphasis on the opioids and cannabinoids.  The major emphasis has been placed on the study of the underlying mechanisms of opioid and cannabinoid tolerance and physical dependence.  This lab also investigates chronic pain via a neuropathic pain model developed in the mouse. Emphasis is placed on the neurochemical events activated in response to chronic pain.
Methodologies employed in this laboratory include behavioral techniques including classical pharmacological procedures to measure pain and its alleviation, immunoblotting, quantitation of blood flow using laser Doppler methods, and sophisticated neurochemical procedures such as the use of HPLC to separate endogenous opioids, measurements of endogenous neuropeptides and second messengers via radioimmunoassay of free intracellular calcium levels in cells using whole-cell imagining, as well as microfluorimetric techniques.
Nick Farrell, Ph.D.
  • Department: Chemistry & Massey Cancer Center
  • Mail: Box
  • Lab: Sanger Hall # 6-004
  • Phone: 828-6320 / 828-1009
  • E-mail: nfarrell@saturn.vcu.edu
    • Research Description: Interaction of novel platimum anti-cancer agents with DNA.

    Undergraduate Projects: Structural and molecular biological experiments to be determined; many undergraduate students have conducted published experiences in the last few years.


    Robert A. Fisher, M.D. Research Description: Small animal transplant tolerance studies; liver cell preparation, preservation and transplantation.

    Undergraduate Projects: To de determined; 4 undergraduate students have conducted published experiences in the last 3 years.

    Carleton T. Garrett, MD, Ph.D. Research Description: The molecular diagnostics laboratory in the Dept. of Pathology has as one of its functions translational research, that is, the development, validation and implementation of DNA/RNA probe-based assays for clinical testing. The laboratory currently offers to the MCV clinical staff quantitative HIV RT-PCR, quantitative HCV RT-PCR, T&B cell gene rearrangements by Southern Hybridization Analysis, Philadelphia chromosome (t9;22) by RT-PCR, detection of the Leiden mutation in the Factor V gene by PCR and detection of the B-cell gene rearrangement by PCR.

    Undergraduate Projects: A number of assays are under development and there are a number of possible projects, generally focused on extending either a molecular technique or extending our understanding of the value of the data obtained with the technique in which a student might participate.

    For this type of research experience to be of benefit to the trainee, we have found that active participation on the part of the trainee is essential. Learning how to do research is, in large part, learning how to critically analyze and solve problems. One does not acquire this skill by osmosis. Every effort is made to provide a trainee with a potentially solvable problem and to help the trainee formulate the problem within the general structure of specific aims, background/significance, experimental design and methodology. However, ultimately, it is the student's effort that determines just how much progress is made.

    Shawn Holt, Ph.D. Research Description: Studies involve human telomerase structure and function.

    Undergraduate Projects: To be Determined


    Todd Kitten, Ph.D. Research Description: Research in the lab concerns virulence of oral streptococci in dental caries and in extra-oral diseases, especially endocarditis.

    Undergraduate Projects: To be Determined


    Aron H. Lichtman, Ph.D. Research Description: The recent identification of cannabinoid receptors distributed heterogeneously in the CNS and the isolation of endogenous cannabinoids suggest the existence of a cannabinoid neuronal system. Therefore, the major thrust of this laboratory is to elucidate the function of the endogenous cannabinoid system and the mechanisms by which the synthetic and naturally occurring cannabinoid agonists interact with this system. The first aim of this project is to identify brain regions that mediate the antinociceptive, cognitive, and motor effects of the cannabinoids. We have focused on the periaqueductal gray, the hippocampus, and the striatum; each of these brain areas contains a high concentration of cannabinoid receptors and plays a role in pain processing, cognition, and locomotion, respectively. A second goal of this project is to examine the impact of chronic cannabinoid administration on behavioral indices and to examine the cellular changes in the relevant brain areas that underlie tolerance. Another ongoing area of research in this laboratory is to characterize the pharmacological effects of abused drugs by inhalation exposure. A trend associated with fears of contracting AIDS and other blood-born diseases is an increased incidence of smoking cocaine, heroin, and other abused substances. In an effort to better characterize the consequences of this route of administration, we are investigating the pharmacological effects of inhalation exposure to opioids, various stimulants, and PCP in laboratory rodents and are also identifying the major pyrolysis products. In particular, the cardiovascular effects of cocaine in the rat and the antinociceptive effects of morphine in the mouse are more severe by inhalation exposure than by intravenous injection.

    Undergraduate Projects: To be Determined


    Joyce Lloyd, Ph.D. Research Description: Our laboratory is interested in developmental gene regulation and uses the switch from expression of the human fetal gamma-globin gene to the adult beta-globin gene as a model system. The study of gamma- to beta-globin switching also has important clinical relevance to the treatment of sickle cell anemia and beta-thalassemia. Gamma-globin has an ameliorating effect in these disorders, so a basic understanding of how switching occurs will lead to novel therapeutic strategies. The major focus of our research projects is to identify the DNA regulatory elements involved in human gamma- to beta-globin gene switching using transgenic mice, and the identification of the transcription factors responsible for the switch. Our laboratory has shown that TATA and CACCC elements in the gamma-globin gene promoter must be present for normal suppression of the beta-globin gene in the embryo. Our working hypothesis is that transcription factors binding to the gamma-globin gene promoter are necessary for a process of promoter competition between the gamma and beta globin genes and the upstream enhancer region called the LCR.

    Undergraduate Projects: Currently the laboratory is working on two major initiatives, and undergraduate students would have a project that would complement these goals. The first initiative is to create large DNA constructs containing the entire 100 kb beta-globin locus with mutations in the gamma globin promoter TATA and CACCC elements, to put these constructs in transgenic mice, and to analyze the effects of the mutations on gamma- and beta-globin gene expression. The second is to identify the transcription factor that specifically binds to the gamma-globin CACCC element.


    Larry Povirk, Ph.D. Research Description: The primary interest of our laboratory is DNA double-strand break repair and its role in mediating gene rearrangements. Double-strand breaks are a particularly severe type DNA damage induced by radiation and by certain antitumor drugs, which can lead to either cell death or chromosome rearrangements if not correctly repaired. Using extracts of eggs from the frog Xenopus, we have recently succeeded in demonstrating repair of double-strand breaks, similar to those formed by radiation, in a cell-free system. This assay is being used to dissect the individual biochemical processes involved in that repair, and to determine the roles of the particular proteins required. At the same time, we are examining gene rearrangements generated by errors in double-strand break repair, in intact irradiated or drug-treated cells. By characterizing these events at both the chromosomal and the DNA sequence level, we are attempting to determine the genetic factors that control the fidelity of repair.

    Undergraduate Projects: For both of the above experimental approaches, short-term, well-defined projects are available, involving either studies of the processing of particular types of DNA breaks in the Xenopus extract system, or characterization of gene rearrangements generated by specific agents in cells with a particular genetic background.


    Patricia W. Slattum, Pharm.D., Ph.D. Research Description: The pharmacokinetics/pharmacodynamics laboratory conducts research on the disposition and response to drugs in humans. We are currently studying the effects of age and gender on the sensitivity to the effects of ethanol and other drugs.

    Undergraduate Projects: Projects in our lab involve collection of blood samples and response measures after drug administration to humans, analysis of blood samples for drug concentration, and mathematical modelling of concentration and response data. A student project could be defined involving any of these aspects of pharmacokinetic/ pharmacodynamic research, and a research experience in our lab will provide exposure to the clinical drug development process in general.

    We have had 2 undergraduate pharmacy students in the PK-PD lab in the past. One analyzed orthostatic test data collected from normal volunteers at screening for drug studies to develop population norms for use in evaluating screening data for future studies. The other has been involved in data collection in the clinic and blood sample analysis for ethanol in elderly volunteers.

    Shirley M. Taylor, Ph.D.

    Research Description: My laboratory focuses on the role of DNA methylation during early development and on the mechanisms controlling the activity of the enzyme responsible for this epigenetic modification, cytosine 5:DNA methyltransferase. We have produced recombinant native and chimeric DNA methyltransferase enzymes, and are beginning to carry out deletion analysis on the regulatory domain.

    Undergraduate Projects: Undergraduate projects would include kinetic analysis of these recombinant enzymes, assistance in the production of truncated enzymes and their characterization and analysis of the locus encoding this protein in order to determine whether alternate forms exist.


    Forrest Smith, Ph.D.
    Department of Pharmacology and Toxicology
    McGuire Hall Annex 324B
    828-5596
    flsmith1@vcu.edu
     
    Research Interests-
    Opioid Tolerance and physical dependence- Opioid tolerance-dependence has been shown to result in significant increases in the activity of the phosphatidylinositol and adenylyl cyclase cascades.  We have demonstrated that drugs that inhibit different steps in each signaling cascade can completely reverse morphine tolerance.  At least 10 isoforms of PKC are expressed in the CNS.  Research has focused on identifying which specific PKC isoforms mediate the expression morphine tolerance by using myristolated pseudosubstrate inhibitors and RACK PKC translocation inhibitors to reverse tolerance. Recent discoveries indicate that tolerance to hypothermia, Straub tail, and multiple forms of analgesia are reversed by PKC inhibitors.  Changes in behavior are being correlated by determination of PKC isoform levels/activity utilizing Western immunoblotting and enzyme assays in specific brain regions.

    Sarah Spiegel, Ph.D. Research Description: Roles of the novel lipid mediator, sphingosine-1-phosphate, in cancer cell biology, neurobiology, and allergic responses.

    Undergraduate Projects: To be Determined Research in Signal Transduction


    Robert M. Tombes, Ph.D. Research Description: Cellular Regulation by Ca2+ and calmodulin dependent protein kinases (CaM kinases). Studies involve the analysis of the nature of the expression and biochemical and functional activity of these isozymes in cell growth and differentiation.

    Undergraduate Projects: Student projects in my lab in the past have involved a wide variety of approaches. Current available projects included the following: 1) The use of PCR (polymerase chain reaction) to identify and clone novel CaMK isozymes. 2) The injection or transfection of mammalian cells in culture with CaMK mutants followed by the analysis of cell cycle parameters and behavior. 3) The analysis of intron/exon boundaries in CaMK genes. 4) Intracellular localization of CaM kinase splice variants using cell fractionation and immunocytochemistry. 5) Characterization of targets of CaMK phosphorylation in signal transduction cascades.

    Kristoffer Valerie, Ph.D.

    Research description: We are studying the mechanisms involved in transcriptional activation by ultraviolet light and ionizing radiation, and other DNA damaging agents. We are particularly interested in the role of chromatin structure in transcription regulation, the interplay between DNA repair and transcription, and the cellular signal transduction processes elicited by DNA damage. We also apply adenovirus-mediated gene delivery into animals in order to sensitize tumors to radiotherapy.

    Undergraduate Projects: To be Determined


    Jenny Wiley, Ph.D. Research description: I examine the behavioral effects of drugs of abuse (primarily, phencyclidine and cannabinoids) and psychiatric drugs (e.g., antipsychotics, antianxiety agents) in animal models.

    Undergraduate Projects: All work with undergraduates would be done with rats or mice; hence, students must be comfortable in learning to handle and inject these animals. Most work involves training the rat or mouse to work for food in a Skinner box and would involve daily (M-F) work, although there are exceptions. Some projects that undergraduate students have worked on include (1) examination of tolerance development to delta-9-tetrahydrocannabinol (the primary psychoactive ingredient in marijuana) and comparison to anandamide, a putative endogenous substance that shares many behavioral effects with marijuana; (2) examination of the effects of atypical antipsychotics on the discriminative stimulus effects of phencyclidine (discriminative stimulus effects are an animal model of subjective effects of drugs in humans); (3) examination of the effects of antipsychotics on patterns of responding; and (4) examination of the effects of intracellular messengers (e.g., nitric oxide modulators) on prepulse inhibition of acoustic startle, an animal model of a type of attentional deficit found in schizophrenia.

    Mark Wood, M.D.

    Research Description: Research projects are available in the Department of Cardiac Electrophysiology in both the basic and clinical laboratories investigating cardiac arryhthmias.

    Undergraduate Projects: Projects in the basic research lab involve studying the electrical properties of isolated cardiac tissue in response to myocardial pacing and arrythmias. Drug studies are also performed in isolated tissue preparations. The clinical projects include the analysis of patient data regarding the clinical use of permanent cardiac pacemakers, implantable cardiac defibrillators and the use of antiarrythmic drugs. Projects involving data acquired in the Clinical Electrophysiology lab are also anticipated. experience with the use of computers or computer program is helpful, but not required.


    Susanna Wu-Pong, Ph.D. Research Description: Cell transport and targeting of biotechnology-derived drugs; intermolecular interactions of oligonucleotides; drug disposition, metabolism and effects during pregnancy.

    Undergraduate Projects: To be Determined


    Dorne R. Yager, M.D. Research Description: The Laboratory of Tissue Repair was set up to facilitate collaborative and interdisciplinary research pertaining to the fundamental biology of tissue repair and fibrosis.  This laboratory is comprised of faculty from the Departments of Surgery, Internal Medicine, and Pediatrics and occupies approximately 4,100 contiguous square feet on the third floor of Sanger Hall.  Ongoing projects focus on regulation of gene expression of the extracellular matrix: in inflammatory bowel disease (Crohn‚s), in dermis during normal wound repair and in chronic non-healing wounds; during fetal dermal wound repair; during wound contraction; and, during the intimal hyperplasia which often occurs following balloon angioplasty, vein grafting and transjugular portasystemic shunts.

    Undergraduate Projects: Techniques utilized by this laboratory are very diverse and include: in utero surgery, many types of RNA and protein analyses, cDNA synthesis and cloning, DNA sequencing, transient and stable transfection assays.  Past undergraduate projects have involved cloning of the hyaluronan synthase genes, utilization of RNase protection assays to quantify transcript levels, and analysis of the expression of the tissue inhibitor of metalloproteinases (TIMP) by dermal fibroblasts.

    Zendra Zehner, Ph.D.

    Research Description: My laboratory is interested in the regulation of gene expression particularly during development and in neoplasia. The intermediate filament protein (IFP) multi-gene family is a good model system for addressing the mechanism(s) of gene expression. Here, we have isolated several cytoskeletal genes including actins and the intermediate filament (IF) gene, vimentin. Vimentin is first expressed at the delineation of the mesoderm and is subject to regulation by several growth factors, i.e., PDGF, FGF and TGF-beta. Several cell types differentiate from this lineage and continue to express vimentin whereas others like muscle, glial, or neurons, "turn off" the vimentin gene and activate the expression of tissue-specific IF genes such as desmin, GFAP, or neurofilaments, respectively. In general, IFP gene expression is regulated at the level of transcription, but vimentin mRNA is also localized in its translation to the region immediately surrounding the nucleus. Since this is also the region from which the filaments grow, co-translation may be crucial for IF synthesis and subsequent polymerization.

    In terms of transcriptional regulation, we have found a unique negative element/factor which represses gene expression. We believe this repression is exerted at the level of transcription initiation. No repressor has been identified which binds to a specific DNA sequence and represses transcription by such a mechanism. Interestingly, this negative factor is missing in metastatic breast cancer cells where vimentin is aberrantly expressed. This suggests that this factor may be a metastatic tumor suppressor, the absence of which permits escape synthesis and alterations in the normal pattern or gene regulation. On the other hand, in normal cells where vimentin is expressed, an upstream, antisilencer element overrides the negative element and restores gene expression. It is through this upstream element/factor that FGF induces vimentin expression. This represents a new and novel FGF-inducible pathway. Work is underway to purify, clone and sequence these two regulatory proteins in order to study their unique mechanism of gene control. Importantly, homologous elements have been found in a variety of other genes including HIV. Therefore, these elements/factors are probably important in regulating the expression of a variety of genes in addition to vimentin.

    In terms of translational regulation, we believe vimentin mRNA localization is attributed to a specific stem/loop structure in the 3'-untranslated region of the mRNA. This region specifically binds a 45-kDa protein which is not vimentin or any other IFP, actin, La, B23, or hnRNPC protein. Studies are underway to also purify and clone this protein in order to investigate its mechanism of mRNA localization.

    Undergraduate Projects: To be Determined


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