Cell and Molecular Biology of DNA Damage/Repair Mechanisms
Shisheng Li, MS, Ph.D.,
University of Wales Swansea, UK

DNA, the genetic material of most living organisms, is under constant assault by endogenous and exogenous agents. A plethora of genotoxic agents exist, from oxidizing chemicals produced naturally in the cell to different type of radiation present in our environment. The DNA damage caused by these agents may interfere with normal cell processes, and if left unattended, the DNA damage may kill the organism or give rise to heritable mutations. To contend with DNA damage, all living organisms use multiple, highly conserved DNA repair pathways. Genetic and biochemical approaches are being used to elucidate the mechanisms of different DNA repair pathways, especially nucleotide excision repair and base excision repair.

Electroinjection, Tumor-Targeted Gene Therapy
Shulin Li, Ph.D.,
Washington State University.

His laboratory is pursuing and building on the development by Dr. Li of a novel protocol for the use of electroinjection as a delivery technique for gene therapy. In this regard, Dr. Li is examining the use of interleukin-12 as a therapeutic agent in the treatment of cancer, with genes for this substance being delivered by electroporation.

Prostate Cancer Metastasis
Inder Sehgal, DVM,
Ohio State University,
Ph.D., Mayo Clinic.

The broad objective of Dr. Sehgal’s laboratory is to investigate mechanisms for prostate cancer metastasis. The basement membrane is a structural matrix that contains cells within their own microenvironments. Prostate tumor cells that become metastatic are able to break through this barrier, in part, by utilizing matrix degrading enzyme systems such as matrix metalloproteinases (MMPs) and the urokinase-plasmin system. The focus of Dr. Sehgal’s research is to identify and explore cellular pathways which regulate these protease systems so that they can be selectively targeted for pharmacologic inhibition.

Pulmonary and Cardiovascular Pathophysiology.
Joseph Francis, B.V.Sc, M.V.Sc., Ph.D.,
Kansas State University

Dr. Francis’s research focuses on the pathophysiology of congestive heart failure. The overall objective of his research is to understand the neurohumoral influence on the progression of heart failure in rodents. Currently, the laboratory is involved in three primary projects. The goal of the first project is to understand the forebrain mechanism regulating gene expression in specific sympathoexcitatory neurons after myocardial infarction. The second project examines the neurohumoral mechanism of cytokine signaling from the heart to the brain in heart failure. The third area of investigation focuses on the hypothalamic mechanisms regulating myocardial protective effect of HMG CoA reductase inhibitors and statin in heart failure. These studies will help in elucidating the role played by the central nervous system in the progression of heart failure and ultimately target the brain for the treatment of heart failure.

Deafness and Experimental Neurology
George M. Strain, Ph.D.
Iowa State University

Electrophysiological and molecular genetic approaches are being taken to identify the causes of deafness that affect as many as 30% within certain dog breeds, with a goal of developing a DNA marker usable for identifying gene carriers. Electrodiagnostic methods are used in the study of other neurologic disorders of domestic animal species, including epilepsy, narcolepsy and spongiform encephalopathies.

Cyclic AMP Signaling Pathways
Masami Yoshimura, D.Sc.
Kyoto University

The long-term goal of my research is threefold: 1) To elucidate the molecular and cellular mechanisms underlying regulation of the cAMP signaling pathway in the central nervous system, 2) To determine the role that the cAMP signaling pathway plays in the physiological and behavioral responses of an animal, and 3) To elucidate the pathways that transduce change in cAMP signaling into the physiological and behavioral manifestations. In particular, I am interested in the effects of ethanol on the cAMP signaling system and the role that this signaling pathway has in an animal’s responses to ethanol. My research program will be interdisciplinary covering molecular biology and pharmacology of the cAMP signaling system, generation of transgenic and gene targeted animals, electrophysiology of neuronal activity, behavioral analysis of model animals, and gene expression study.

Diabetes Research
Henrique Cheng, D.V.M., Ph.D.,
Iowa State University

Increases in intracellular calcium concentration are a ubiquitous signaling mechanism that is essential for physiological responses, including secretion, contraction, gene transcription, differentiation and apoptosis. So the question of how calcium is regulated within cells is fundamentally an important one. Our research is focused on the cellular and molecular pathways involving calcium signals in both excitable and non-excitable cells. One project examines the regulatory mechanisms controlling insulin secretion in pancreatic beta cells and their impact on diabetes. A second project examines the regulatory mechanisms controlling stem cell differentiation. Our laboratory utilizes fluorescent imaging, electrophysiology and molecular biology to investigate the properties of ion channels and calcium mediated events.

Analytical Toxicology and the Neurochemistry of Hallucinogens.
Steven A. Barker, MS, Ph.D.,
University of Alabama in Birmingham

Research into the adsorption, distribution, metabolism and clearance of hallucinogens, their mechanisms of action and role as naturally occurring neurohormones. Studies are directed at characterization of neural pathways affected by drugs and their related roles in the regulation of perception/cognition in health and disease. Research and training in the use and application of advanced mass spectrometric techniques [GC, LC/MS/MS, capillary LC/quadrupole/time-of-flight (QToF)] for the analysis of trace neurotransmitters, drugs and drug metabolites and for proteomics is also conducted.

Ecological Chemistry
James Catallo, Ph.D.,
College of William and Mary.

High energy aqueous organic chemistry (near and super-critical, sonochemical); polycyclic aromatic hydrocarbons and N, O, and S- heterocyclic aromatics in air, sediment, water and biological systems; instrumental electrochemistry; bioenergetics, time series data acquisition/spectral analysis; stable isotope organic chemistry; organic geochemistry; environmental chemistry of wetlands and coastal marine systems; environmental restoration/remediation; covariance structure/path/causal analyses; structural equation modeling; quantitative analyses of quasi-experiments; quantum mechanical modeling/chemical property prediction.

Aquatic Animal Pharmacology, Toxicology and Physiology
Kevin M. Kleinow, DVM/Ph.D.
University of Minnesota and the University of Wisconsin-Milwaukee

Mechanistic research examining the relationship between xenobiotic biotransformation, multidrug resistance transporter function and bioavailability in aquatic and mammalian species. Current studies are directed towards characterization of these processes as related to drugs, carcinogens and contaminants.

Respiratory Research; Environmental Agents in Atherosclerosis.
Arthur Penn , Ph.D.
University of Pennsylvania

This laboratory focuses on roles and mechanisms of action of environmental agents, especially inhaled toxicants, on atherosclerosis and respiratory disease. A recent focus of research has been on the effects of environmental tobacco smoke and industrial combustion products on acceleration of asthma and atherosclerosis. A fully equipped inhalation facility is available for carrying out exposures to individual agents and complex mixtures.

Cell and Molecular Biology of Tooth Eruption.
Gary E. Wise, Ph.D.
University of California , Berkeley

Multiple approaches are used to determine what are the signaling molecules that initiate the cellular events involved in tooth eruption.  A hypothesis has been developed that suggests a signaling cascade of inflammatory cytokines and growth factors is necessary.  Ultimately, there is chemotactic recruitment of mononuclear cells to the dental follicle, and these cells then fuse to form osteoclasts that resorb the alveolar bone to form an eruption pathway.  Current studies are elucidating the regulation of the molecules necessary for osteoclast formation to occur.  Various techniques include RT-PCR, cell culture, chemotactic assays, Western blotting, immunocytochemistry, TRAP assays and Southern blotting.