Peter Angeletti, Ph.D., Assistant Professor, School of Biological Sciences, Nebraska Center for Virology - UN-L.  My research is focused on three main topics relating to sexually transmitted Human papillomaviruses (HPVs). The first area of emphasis is in the analysis of cis and trans-acting signals required for stable replication of HPVs. A second area under study is the specific DNA packaging requirements of HPVs. In both of these studies, we make of use of a novel and convenient yeast platform to model HPV functions and to identify cellular factors involved. A final area of interest for the lab is the analysis of HPVs in HIV positive patients in Zambia Africa. In these studies we will determine the extent to which HIV influences the rate of HPV infection and the rate of progression of HPV lesions to cancer.

Surinder Batra, Ph.D., Professor, Department of Biochemistry and Molecular Biology and Eppley Cancer Center - UNMC.  Research interests are in investigating the regulatory mechanisms in cells that are altered due to environmental insults.

Rick A. Bevins, Ph.D., Professor, Department of Psychology - UNL.  My research program on the etiology of drug abuse bridges areas of neuroscience, pharmacology, endocrinology, immunology, and animal learning and cognition.  With the motivated effort of exceptional graduate and undergraduate students and the consistent support of the Psychology and Biological Sciences Departments, as well as the College of Arts and Sciences and extramural funding agencies such as NIH, we have made great progress in answering important questions related to drug abuse.  In this research effort, we use preclinical animal models to understand factors involved in the development and maintenance of drug addiction.  This research includes assessment of the behavioral and neuropharmacological factors affecting the ability of drug cues to acquire new meaning and hence control over behavior.  Other research effort focuses on novelty and sensation seeking, learned associations between environmental cues and abused drugs (source of cravings), and immunotherapy (vaccine) techniques against drug addiction. 

Lloyd Bullerman, Ph.D., Professor, Food Science & Technology - UNL. Dr. Bullerman's research deals with studying 1) molds and mycotoxins in foods, including storage and deterioration of cereal grains; 2) effects of antifungal substances (chemicals, herbs and spices) and competitive microorganisms (lactic acid bacteria and other molds) on mold growth and physiology of mycotoxin production; 3) incidence and toxicology/carcinogenicity of Fusarium moniliforme and its metabolites, the fumonisins, in corn and other commodities. Interests extend also to other Fusarium species and toxins.

Ercole Cavalieri, D.Sc., Professor, Eppley Institute for Research in Cancer and Allied Diseases; Director, Center for Environmental Health and Toxicology, College of Public Health; Courtesy Professor, Biochemistry & Molecular Biology - UNMC. The major portion of the research in Dr. Cavalieri's laboratory deals with molecular mechanisms of tumor initiation by polycyclic aromatic hydrocarbons (PAH) and estrogens. Particular emphasis is placed on metabolic activation of PAH by one-electron oxidation. This research includes (1) synthesis, chemical properties and reactions of mechanistic interest of PAH radical cations, (2) in vitro and in vivo studies of the covalent binding of PAH to DNA and determination and quantitation of PAH-DNA adduct structures, (3) correlation between depurinating DNA adducts and H-ras oncogene mutations, and (4) chemical mechanisms of catalysis by cytochrome P450. The areas of research in estrogens include (1) discovery of the estrogen metabolites involved in the etiology of human cancer, (2) determination of the depurinating DNA adducts of catechol estrogen quinones, (3) determination of biomarkers for susceptibility and early detection of breast, prostate and other human cancers, and (4) development of strategies for cancer prevention.

Ronald Cerny, Ph.D., Associate Research Professor, Department of Chemistry and Director of Services, Nebraska Center for Mass Spectrometry - UNL.

Dhrubajyoti Chakravarti, Ph.D., Research Assistant Professor, Eppley Institute for Research in Cancer and Allied Diseases - UNMC.  The primary focus of our research is to understand the very early events of cancer (the biology of initiation).  We are analyzing how DNA damage caused by a group of endogenous (estrogens) and environmental carcinogens (polycyclic hydrocarbons) leads to mutations that transform normal cells into a cancer cells.  We have found that many of these carcinogens form primarily unstable DNA adducts, which are spontaneously lost from DNA, leaving abasic sites behind.  We have found that the repair of these abasic sites is error-prone and results in mutations. We are currently investigating mechanisms that induce errors in the repair.
    Some of the cells mutated by this pathway become cancer cells.  The number of these cells determines the eventual tumor yield.  We found that under certain conditions, these early cancer cells proliferate without any promoting treatments.  This observation allowed us to investigate a second question: to what extent do the early cancer cells account for eventual tumor burden?  To identify factors which control their proliferation and also, to understand the mechanisms involved, we are studying cell cycle (G1-S transition) parameters associated with the early proliferation of these cells.  We expect that lessons learned from the studies on error-prone repair of carcinogen-induced abasic sites will be useful in developing strategies for cancer prevention. In addition, the studies on proliferation of the nascent cancer cells may be useful in developing strategies for early intervention.

Wing C. (John) Chan, M.D., Professor, Pathology and Microbiology; Co-Director, Center for Lymphoma & Leukemia Research - UNMC.  Dr. Chan's research group is using microarray technology to gain a better understanding of the basic mechanisms in lymphoma.  The goal is to provide a more effective way to determine the diagnosis and prognosis of patients with lymphoma and to find targets that can be used to develop novel therapies, leading to better treatment and survival.  The gene expression profiles of close to 1000 cases of lymphomas have been determined in the last few years in collaboration with a large international consortium - the Lymphoma/Leukemia Molecular Profiling Project (LLMPP).  As an extension of this effort, a specialized microarray, including all known diagnostic and prognostic parameters for non-Hodgkin's lymphoma has been designed.  Dr. Chan and his colleagues will use this CHIP to validate and refine current as well as newly-discovered molecular signatures and diagnostic algorithms that will lead to higher accuracy for diagnosis and prognostication of all forms of lymphoma in the next 5 to 10 years.

Samuel M. Cohen, M.D., Ph.D., Chairperson and Professor, Pathology and Microbiology and Havlik/Wall Professor, Oncology - UNMC.  Dr. Cohen's research involves several aspects of chemical carcinogenesis utilizing the urinary bladder as a model system. These studies include short and long-term bioassays, molecular biological evaluations of oncogenes and suppressor genes during carcinogenesis, cell biology, toxicology, metabolic activation of carcinogens, and DNA adduct studies, as well as computer modeling. These investigations are aimed at a better understanding of the cellular and molecular mechanisms involved in urinary bladder carcinogenesis, with comparative evaluations of the processes in animal models compared to the human disease. Model systems being evaluated include arsenicals and PPARg agonists.  Interactions with industry groups and the Environmental Protection Agency and Food and Drug Administration are ongoing. 

Patrick Dussault, Ph.D., Chair and Professor, Chemistry - UNL.  Our research in toxicology focuses on two areas. 1) Peroxides, unstable compounds containing a reactive O-O bond, are formed in man through both enzymatic and chemical oxidation of polyunsaturated fats, and may be involved in aging, the asthmatic response, heart disease, carcinogenesis, and a variety of inflammation-related diseases or conditions.  However, there are few effective methods allowing the synthesis of peroxide natural products for biomedical study.  Research in our labs focuses on new methods for peroxide synthesis based upon new oxidation methods (ozone, singlet oxygen, triplet oxygen, hydrogen peroxide) and new carbon-carbon bond constructions.  2) In collaboration with researchers in the biological, nutritional, and plant sciences, we are applying synthetic chemistry to investigations of small molecule-based signaling.  For example, the sesquiterpene farnesol is the factor responsible for regulating cell morphology in the pathogenic fungi Candida albicans.  We are currently using synthetic farnesol analogs as a tool to investigate this process and to better understand the role of fungal morphology in attack on a host.

Eric Y.K. Fung, Ph.D., Professor, Oral Biology, College of Dentistry - UNMC.  Dr. Fung's research focus is on determining how different neurotransmitter systems in the brain regulate behavioral changes. His studies have involved determining the effects of chemicals injected directly into specific areas of the brain e.g. the nucleus accumbens, corpus striatum, globus pallidus and substantia nigra on motor function. Dr. Fung has been studying the behavioral and biochemical changes in laboratory animals due to chronic administration of nicotine and the impact of nicotine withdrawal on the nicotinic and dopaminergic systems of the striatal and mesolimbic areas. Dr. Fung has conducted studies to determine if there is any correlation between body (blood, urine and tissue) concentrations of mercury and the occurrence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. At present, he is studying the effects of nicotine on bone modeling, remodeling, and the mechanism by which nicotine may affect bone homeostasis. Another project involves examining the pharmacokinetics of bisphenol A released from dental sealant.

Janee Gelineau-van Waes, D.V.M., Ph.D.,  Scientist, Munroe-Meyer Institute; Assistant Professor, Genetics, Cell Biology and Anatomy; Courtesy Assistant Professor, Pharmacology - UNMC.  Research in Dr. Gelineau-van Waes’ laboratory focuses on mechanisms of teratogenicity.  Of particular interest is the interaction between specific genes and environmental toxicants and pharmaceuticals as they influence normal embryonic development.  Potential mechanisms of genetic susceptibility to environmentally-induced birth defects are investigated by analyzing candidate genes involved in determining susceptibility to neural tube defects, craniofacial malformations, and congenital heart defects.  Gene expression patterns during critical periods of development are analyzed using in situ transcription and cDNA microarray methodologies to quantitatively examine changes in mRNA and develop a comparative molecular fingerprint for isolated tissues during embryogenesis in murine animal models that have been exposed to teratogens.  Follow-up studies are done using in situ hybridization, immunohistochemical techniques, and confocal imaging.
    In addition, transgenic mouse strains have been developed to study the role of maternal folate supplementation in the prevention of congenital birth defects.  Studies are being performed utilizing mouse models in which the folate binding protein genes Folbp1 and Folbp2 have been knocked out. Heterozygous animals have significantly decreased serum folic acid levels and increased serum and brain homocysteine levels when dams are maintained on a low folate diet.  Embryos homozygous for the Folbp1 null allele die in utero by gestational day 10, with serious congenital malformations.  When Folbp1 heterozygous dams are placed on high levels of folate supplementation, it is possible to completely rescue the nullizygous phenotype, although neonates must be maintained on high levels of folate to survive.  Conversely, when Folbp1 heterozygous dams are placed on low levels of folate supplementation, the nullizygous fetuses survive to term, but present with severe neural tube (exencephaly), craniofacial (cleft lip/palate), and heart malformations (persistent truncus arteriosus, ventricular septal defects).  Since supplemental folic acid has been shown to reduce the risk for these congenital malformations in humans, the Folbp1 knockout mouse provides a useful model to study potential mechanisms of protection.  While Folbp2 nullizygous mice are born phenotypically normal, recent studies have shown that they are exquisitely sensitive to environmental contaminants such as arsenic, and prenatal exposure to such compounds predisposes them to a number of neural crest cell-derived birth defects.  Current efforts are also underway to characterize the role of folate transport during embryogenesis in the reduced folate carrier (RFC) knockout mouse.
    Another research focus involves the role of pharmaceuticals in teratogenesis.  Using mouse models we are trying to identify specific alterations in gene expression and function that can explain the craniofacial dysmorphia observed in human infants exposed in utero to the anticonvulsant drug phenytoin.  Prenatal exposure to this drug significantly increases expression of several isoforms of retinoic acid receptor genes, ligand-inducible members of the steroid hormone superfamily of transcription factors.  This data, coupled with competitive receptor binding assays, suggest that a metabolite of phenytoin may be acting as a retinoic acid agonist.  It is therefore possible that the craniofacial dysmorphogenesis seen following phenytoin exposure could be related to altered expression of the retinoic acid receptors and retinoic acid response element (RARE)-regulated downstream growth factors.  Efforts are currently underway to characterize the functional significance of a truncated RARalpha transcript observed in target tissues following in utero exposure to teratogenic concentrations of phenytoin.

Vadim Gladyshev, Ph.D., Associate Professor, Biochemistry - UN-L.  We are trying to understand the mechanism of redox regulation of cellular processes.  Our focus is on reactive oxygen species (ROS) and thiol-disulfide oxidoreductase functions of cellular components.  Little is known what are specific targets of ROS and how oxidant and antioxidant signals are transmitted in the cell.  To understand the mechanism of redox regulation, we need to know the identities and functions of most of the participants in the redox process.  Thus, we are developing and employing various bioinformatics approaches that take advantage of genome sequencing, proteomics and functional genomics projects, and which are followed with in vitro and in vivo tests of the in silico predictions.
    In mammals, two major redox systems, thioredoxin and glutathione systems, are dependent on the trace element selenium, which is an essential component of various redox enzymes.  Selenium is present in proteins in the form of the 21st amino acid, selenocysteine (Sec). Sec is co-translationally inserted in protein in response to the UGA codon with the help of the SECIS element, an mRNA stem-loop structure present in 3’-untranslated regions of selenoprotein genes.  Because UGA is interpreted as a stop signal by available gene annotation tools, selenoprotein genes are typically annotated incorrectly in sequence databases, including published human genome assemblies.  To overcome this problem, we are identifying selenoprotein genes by genome-wide searches for structural and thermodynamic properties of SECIS elements.  We also are identifying other redox proteins by genome-wide searches for specific redox motifs present within secondary structure patterns.  Subsequently, we are characterizing functions, regulation and specific targets of selenoproteins and other important redox enzymes to gain a system-wide view on redox regulation of cellular processes.
    One of our current projects involves the 15 kDa selenoprotein (Sep15).  We identified Sep15 as a candidate protein that mediates the cancer chemopreventive effect of selenium.  We currently are characterizing its function and role in cancer prevention to identify a mechanism by which dietary selenium decreases cancer incidence.  Another project involves the functional characterization of animal thioredoxin reductases (TRs).  Mammals evolved three thioredoxin reductases: cytosolic TR1, testes-enriched TR2 and mitochondrial TR3.  Each of these proteins occurs in multiple forms that are generated by alternative first exon splicing.  In addition, TR2 is a natural fusion of TR and glutaredoxin domains, may function as thioredoxin and glutathione reductase (TGR) and appears to be involved in male reproduction.  We recently found that Selenoprotein R (SelR), one of the selenoproteins that we initially identified through bioinformatics searches for SECIS elements, functions as methionine-R-sulfoxide reductase.  Methionine sulfoxide reduction has been implicated in regulating the lifespan in animals.  We would like to determine the role of SelR in aging as well as the mechanism by which methionine sulfoxide reduction regulates lifespan.
    We hope that our studies will provide a better understanding of the role of redox processes in physiological and pathophysiological states, particularly in regard to cancer, aging and male reproduction, and will lead to new therapeutic and disease-preventive agents.

Whitney Goldner, M.D., Assistant Professor, Internal Medicine - Diabetes, Endocrinology and Metabolism, College of Medicine - UNMC.  I am currently evaluating the spatial distribution of thyroid cancer in the state of Nebraska using spatial statistics, a novel evaluation tool for low incidence diseases.  We are also determining whether there is a correlation between well water atrazine, alachlor, and gross alpha particle levels and the distribution of thyroid cancer in the state.  I am also looking at the relationship between thyroid disease and known pesticide exposure.  We are using the Agricultural Health Study database and looking at incident and prevalent cases of thyroid disease and correlating them to reported pesticide exposures in the spouses of the pesticide applicators.  We recently obtained IRB approval to start a clinical thyroid cancer and thyroid nodule database at the University of Nebraska Medical Center that will obtain not only demographic information, but also exposure history, occupation, family history, dietary history, medications, and past medical history.

Timothy Greiner, M.D., Associate Professor, Pathology and Microbiology - UNMC.  Dr. Greiner's research focuses on the analysis of the molecular epidemiology of lymphomas in rural Eastern Nebraska associated with pesticide exposure by examining p53, bcl-6 and bcl-2 mutations by denaturing gradient gel electrophoresis and automated fluorescent sequencing Characterization of T-cell lymphomas by denaturing gradient gel electrophoresis.  Analysis of the mutations in EBV-genes (LMP-1, EBNA-1) in post-transplant lymphoproliferative disorders.

F. Edwin (Ed) Harvey, Ph.D., Associate Director and Professor, School of Natural Resources; Director, Justin Smith Morrill Scholars Program; Supervisor, Groundwater Chemistry Laboratory - UNL.  My research uses dissolved major ions, nutrients, and trace metals in natural waters in conjunction with the stable and radioactive isotopes of water and its dissolved constituents to trace water movement within the hydrologic cycle, and to understand the geochemical evolution of water and its impact on ecosystems and the environment. Some examples of my research include; (a) investigating the role of saline groundwater in the development and sustenance of Nebraska’s eastern saline wetlands - home to a number of unique or endangered species including the Federally listed Salt Creek Tiger Beetle (Cicindela nevadica var. lincolniana), (b) determining the hydrologic connection between Rainwater Basin wetlands and underlying groundwater and evaluating the role of these wetlands on the transport and/or remediation of agricultural chemicals such as nitrogen and atrazine, (c) an ongoing chemical and isotopic characterization of groundwater within the Dakota Aquifer in Nebraska, (d) a study using the ¹⁸O/¹⁶O and ²H/¹H ratios of precipitation, soil porewater, groundwater and plant xylem water to quantify the spatial utilization of soil water by trees (Pinus ponderosa and Juniperus virginiana) and dominant C₄ grasses (Schizachyrium scoparium and Panicum virgatum) in the Nebraska Sandhills; (e) a study to evaluate the presence and impact of elevated arsenic levels in public drinking water supplies across the state and (f) research to determine the δ³⁷Cl, δ¹⁵N, δ¹³C and δ²H isotope ratios of atrazine and other herbicides and their breakdown products and the potential for using isotopes to identify and track agricultural contaminant sources.

Steven Hinrichs, M.D.,  Senior Associate Dean for Research, College of Medicine; Professor and Director, Microbiology and Virology Laboratory, Department of Pathology/Microbiology; Courtesy Professor, Eppley Institute for Research in Cancer and Allied Diseases, Department of Orthopaedic Surgery; and, Associate Faculty, Creighton University/University of Nebraska School of Medicine, Pediatric Infectious Disease Division.   My academic research activities are centered in two areas, including cancer biology and infectious diseases. The research activities have considerable overlap when studied at the molecular level and provide the opportunity for insights into many issues of clinical relevance.  I am interested in how infectious diseases and viruses in particular are involved in the development of the neoplastic process or complicate its treatment.  We have developed a model system for inhibiting the transcriptional activation process resulting from infection by HTLV-1 whereby the Tax protein up-regulates expression of a variety of other genes through a cyclic AMP responsive element.  We identified a monoclonal antibody that blocks the binding of ATF-1 to DNA with an accompanying decrease in transcriptional activation.  The complementarity determining regions of this antibody have been cloned into a functional scFv that can be expressed in cells.  The relevance of this approach comes with the knowledge that many characteristic chromosomal translocations incorporate the transcriptional activation domain of one gene and the DNA binding domain of a second gene.  We have shown that one example of such a fusion gene is overexpressed and is critical for the maintenance of proliferation in a sarcoma.  We are now using x-ray crystallography to examine the interactions between the CDRs of the antibody and its epitope to gain more insight into key molecular interactions and possible future developments of carbon-based inhibitory molecules.  The second aspects of cancer and infectious diseases relates to the complications of treatment of patients who are immunosuppressed. One of the most insidious infections is that by molds and fungi which reside in the environment and present minimal threat to immunocompetent individuals.  We have developed novel molecular detection strategies that can also be used to identify the specific fungus at the species level in blood and/or tissue.  These efforts have been recently expanded to successfully identify all known pathogenic and opportunistic fungi.

Kyle Hoagland, Ph.D.,  Professor, School of Natural Resources - UNL.  Research interests include aquatic ecology, water quality/limnology, attached algal ecology, effects of riparian buffer strips on agricultural streams, physiology and biochemistry of diatom adhesion to submerged surfaces, impacts of pesticides on aquatic communities, and global warming effects on lakes.

Thomas Jerrells, Ph.D.,  Professor, Pathology and Microbiology - UNMC.  Research in the laboratory involves the evaluation of immune responses to model infectious agents including listeria monocytogenes, murine cytomegalovirus, and Salmonella typhimurium to test the effects of ethanol consumption on systemic and mucosal immune responses.  Both in vivo and in vitro models are used to study the role of alterations in cell-mediated immune responses to antigenic epitopes that stimulate CD4 and CD8 lymphocytes.  An emphasis is also on the role of immune responses to the pathogenicity of the infectious agents.  We are especially interested in the role of immune responses in the liver damage associated with chronic viral infections.  These effects appear to be associated with activation of cytotoxic T cells that kill hepatocytes either through a perforin/granzyme or FAS/FAS-ligand pathways.  Both are under investigation at this time.  One major area of investigation in the laboratory is investigation of the role of corticosteroids in the immune suppression associated with ethanol consumption and dioxin.

Alexander Kabanov, Ph.D., Parke-Davis Professor of Pharmaceutical Sciences, College of Pharmacy and Director, Center for Drug Delivery and Nanomedicine - UNMC.  Nanomedicine develops materials and devices operating at the nanoscale to diagnose, treat and monitor diseases. It is expected that nanomedicine would yield implantable devices, 100,000 times smaller than the head of a pin, which will effectively detect diseases without surgical invasion and then eradicate the diseased cells by precisely “pumping” medicine to them. The nanomedicine field joins engineering science with pharmaceutical and medical sciences to translate advances in nanotechnology research into clinical practice. Several nanomaterial-based therapies have already been approved for clinical use and many more nanomaterials are evaluated in clinics. Thus nanomedicine is both “a futuristic” and “a realistic” field with a near-term prospective to improve human health. To address this goal the University of Nebraska Board of the Regents has established the Center for Drug Delivery and Nanomedicine (CDDN) in October 2004. CDDN develops innovative approaches to deliver drugs, genes and imaging agents through nanotechnology to maximize clinical benefit while limiting untoward side effects. Our research is focused on diseases that currently have no cure and only limited palliative therapy including cancer and degenerative diseases, such as Parkinson’s and Alzheimer’s disease. CDDN currently has 38 world class researchers from clinical and basic sciences departments representing two major campuses of the University of Nebraska, University of Nebraska Medical Center (UNMC) and University of Nebraska-Lincoln (UNL), and the Creighton University. CDDN is administered through the UNMC College of Pharmacy.  In summary our Center 1) provides an integrated focus in drug delivery and nanomedicine; 2) supports research and training of new and established investigators; 3) links scientists in several campuses across the State of Nebraska; 4) combines the intellectual and technological capabilities of these campuses to develop innovative nanotechnologies; and 5) facilitates the transfer of these technologies to biomedical scientists. CDDN integrates expertise in drug delivery, gene therapy, neuroscience, medicine, cancer biology, polymer science, nanotechnology and engineering to make breakthrough advances in nanomedicine to improve well-being of the citizens of our State and the society at large.

Shirpat Kamble, Ph.D., Professor, Entomology - UNL.  Dr. Kamble is principal investigator on projects on urban entomology.  The specific research areas are:  fate of insecticides in soils and urban environment, molecular toxicology, baiting technology as alternative to pesticides.  The laboratory facilities include HPLC, gas chromatography, PCR, ultracentrifuge, gel electrophoresis units, growth chambers, and other necessary equipment. 

Alan Kolok, Ph.D., Associate Professor, Biology - UNO.    Dr. Kolok's research emphasizes the physiology and genetics of resistance to toxic compounds.  The laboratory primarily uses fathead minnows as a model organism, and is interested in the response of these fish to metal exposure.  Metal susceptibility is generally correlated with impaired function of gill ATPase ion pumps, and ionoregulary failure, however in many of the published studies all of the individuals respond to metal exposure uniformly.  This is not the case for fathead minnows, as some individuals are resistant to the exposure, while others are highly susceptible.  Kolok's laboratory has perfected a method by which susceptible individuals can be identified while they are still alive.  Using this methodology, the laboratory is beginning to conduct breeding studies to develop highly susceptible and highly resistant strains of fish.  These strains of fish will be used to detail the physiological and genetic differences between metal susceptible and metal resistant individuals.

Oksana Lockridge, Ph.D., Professor, Eppley Institute for Research in Cancer and Allied Diseases - UNMC.  Specialty area of research is in organophosphorus pesticides.  We are developing mass spectrometry methods to identify proteins that react with organophosphorus pesticides.  Our long-range goal is to understand why some people are incapacitated after low dose exposure to organophosphorus pesticides, whereas others have no ill effects from the same dose.  We also want to understand why some people have cognitive deficits, muscle weakness, and gastrointestinal problems for years after a low dose exposure.  Organophosphorus pesticides are widely used in agriculture as well as in homes and gardens. 

Parmender Mehta, Ph.D., Associate Professor, Biochemistry and Molecular Biology - UNMC.  Research is focused on cell-cell communication mediated by gap junctions.  Gap junctions are unique macromolecular structures that provide a direct intercellular pathway for the diffusion of growth-regulatory molecules (≤1 kDa) between the cytoplasmic interiors of contiguous cells.  The constituent proteins of gap junctions are coded by a family of 20 related but distinct genes called connexins.  Dr. Mehta is extremely interested in investigating how environmental chemicals influence assembly and disassembly of connexins into gap junctions as well as in elucidating the molecular mechanisms involved.

Jane Meza, Ph.D., Associate Professor, Division of Biostatistics, College of Public Health.  Dr. Meza's research focuses on design and analysis of clinical trials, especially cancer clinical trials and studies of the treatment of childhood cancer, especially soft tissue sarcoma, cancer control and nursing research.  Dr. Meza’s methodological research focuses on survey methodology and statistical issues related to small-area estimation.  These methods have been extended to disease mapping applications (Meza. “Empirical Bayes Smoothing of Relative Risks in Disease Mapping.”  Journal of Statistical Planning and Inference, 112:43-62) and combining national and state data to estimate the probability of a rare event (Buskirk and Meza. “Estimating Lifetime Drug Use Rates with National and State Survey Data.” Journal of Official Statistics, 19(3): 237-252).

Sidney Mirvish, Ph.D., Professor, Eppley Institute for Research in Cancer and Allied Diseases; Courtesy Professor, Pharmaceutical Sciences, College of Pharmacy - UNMC. Dr. Mirvish performs research on the chemistry, biochemistry and biological action of a group of cancer-inducing chemicals called nitrosamines and related chemicals such as nitrate, nitrite, and nitrite esters. Current research includes the following studies: a) The biochemistry and biology of nitrosamine carcinogenesis in the rodent esophagus and similar studies on human esophagus. These studies involve the production by esophageal and liver microsomes of stable hydroxy derivatives and aldehydes from nitrosamines; the induction in rats of lower esophageal adenocarcinomas, a type of cancer that is increasing in the U.S.A.; the mutagenic action of nitrosamines in a bacterial test, and the alkylation of esophageal DNA by nitrosamines; b) The formation of N-nitrosoproline and other markers of nitrosamine formation in the human stomach from ingested nitrate. This study involves the measurement of nitrosoproline, nitrate and nitrite in the urine and saliva of people consuming proline and nitrate; c) The reaction between amino acids and nitrite to produce alkylating agents; d) Chemical and toxicology identification of the "total nitroso compounds" that occur in meat products and in human gastric juice and feces; e) Inhibition of nitrosamine metabolism by isothiocyanates and allyl sulfides that are formed from cabbage and garlic.

Daniel Monaghan, Ph.D., Professor, Pharmacology and Experimental Neurosciences - UNMC. Glutamate is the predominant excitatory neurotransmitter in the vertebrate brain. An understanding of glutamate's role in neurotransmission has led not only to major breakthroughs regarding mechanisms of brain function at a cellular level, but also to the finding that glutamate receptors are involved in a variety of neurotoxicities and neuropathologies. Chemicals that over-activate any of a variety of glutamate receptors in the brain can cause cell death. Also, a wide variety of chemicals kill brain cells by indirectly activating glutamate receptors. For example, agents that compromise energy production (e.g. electron transport chain inhibitors) lead indirectly to chronic glutamate receptor activation which in turn kills the cell. In collaboration with Dr. Rosenquist at UNMC, our lab has recently found that chemicals that interact with glutamate receptors can cause major teratogenic effects on embryo development by a mechanism not yet understood. In our laboratory we are using the techniques of molecular biology, protein chemistry, quantitative receptor autoradiography, in situ hybridization, and electrophysiology to determine the biochemical and physiological properties of glutamate receptor subtypes.. In particular we are interested in the NMDA type of glutamate receptor since this type is critically involved in learning and memory as well as various neuropathologies. We are also examining how growth factor receptor signal transduction pathways can modulate the function of glutamate receptors in brain in normal and diseased states.

Hideaki Moriyama, D.En., Associate Professor, Biology - UNL.  Mercury is released into the environment by volcanic activity and the utilization of fossil fuels, and it circulates the earth's surface.  The major chemical form of mercury in the environment is mercury sulfide, which is stable (inactive).  However, methyl mercury penetrates our bodies through food, especially via aqueous organisms.  At low levels, mercury has little effect on human health.  However, at high concentrations, numerous problems have been reported.  It is because mercury possesses similar physical and chemical properties of biologically important metals such as copper and zinc that the uptake of mercury results in significant metabolic disorders similar to those resulting from the uptake of cadmium (Cd) and selenium (Se).  The systematic elucidation of interactions between mercury and biological macromolecules is important to both clinical understanding and nutrition concerns.  Mercury is used in protein crystallography as a heavy atom regent for determining phase information, and many three-dimensional biological macromolecular structures featuring coordinated metals are available in the Protein Data Bank.  Using this structural information as training data, we propose to develop methods to identify metal-binding proteins from unannotated genomic information, including that from human.  Specific aims include: 1) identifying mechanisms of metal coordination in biological macromolecules at the atomic level using the Protein Data Bank; 2) developing methods for classifying metabolic metallo-proteins using genomic information from the National Center for Biotechnology Information; and 3) reconstructing symbiotic systems to introduce interactive and non-interactive metabolism.

Daniel Murman, M.D., Associate Professor, Neurological Sciences - UNMC. 

Charles Murrin, Ph.D., Professor and Vice-Chairperson, Pharmacology and Experimental Neurosciences; Courtesy Professor, Neurological Sciences - UNMC.  The development of the central nervous system is a complex process in which billions of cells become organized anatomically, biochemically and physiologically to form the functioning central nervous system.  Our understanding of how this development is controlled and regulated is very limited. The goal of the research in Dr. Murrin's laboratory is to study this development and its regulation by examining chemically defined neuronal systems. Their  studies are designed to address two questions: 1. What is the normal developmental pattern for different aspects of specific neurotransmitter systems, and 2. How do these neuronal systems interact during development.

Youri I. Pavlov, Ph.D., Associate Professor, Eppley Institute for Research in Cancer and Allied Diseases; Courtesy Associate Professor, Pathology and Microbiology - UNMC.  Genetic stability depends on the high fidelity of chromosomal DNA replication, which is achieved by several sequential processes.  Mutations in genes affecting any of these systems are global mutators, greatly enhancing mutation rate and drastically decreasing viability due to cancer onset. Examples are defects in 8-oxo-dGTPase or proofreading by polymerase d in mice, defects in mismatch repair in families with hereditary nonpolyposis colorectal cancer, or a defect in DNA lesions bypass in XP-V patients in humans.  Being deleterious, global mutators cannot account for evolutionary and developmental p4rocesses in eukaryotes in the situations when high level of mutagenesis is desired.  Current evidence suggest6s that mutation rates differ significantly along the genome.  The most striking example of such variation comes from the immunology field.  In specialized cells responsible for antibody production the variable regions of immunoglubulin genes have six orders of magnitude higher mutation rates than other genes.  One current hypothesis explaining the hypermutation phenomenon is site-directed damage to DNA by cytidine deaminase and recruitment of a specific error-prone polymerase for replication/repair of these genes.  Differential mutability of certain regions of the genome in certain tissues could be critical to life and evolution.  One example of human disease associated with mutability of selected genes is fragile X and Huntington disease, which depend on expansion of triplet repeats in certain region of chromosome.  WE are creating novel systems to study the fidelity of isolated DNA polymerases in vitro in DNA and chromatin templates representing critical eukaryotic genes, e.g. immunoglubulins or cancer susceptibility genes.  Inventory of mutational signatures of individual replication components enables to find these signatures in mutational spectra of selected human or mouse genes critical for a disease.  We also overexpress in yeast human cytosine deaminases, implication in stomatic hypermutation of immunoglubulin genes, RNA editing and antiviris defense.  In order to study local control of mutagenesis, we utilize the systems that were developed previously to study replication and repair fidelity along yeast chromosomes.  We investigate the mechanisms of differential mutability by identifying genes or chromosome regions affecting the distribution of mutation events along the chromosomes in trans or cis positions.  We use several traditional molecular genetics model objects, primarily baker's yeast Saccharomyces cerevisiae.

Richard Pleus, Ph.D., Adjunct Associate Professor, Pharmacology and Experimental Neurosciences - UNMC.  Research focused on human health risk, including mode-of-action studies aimed at quantifying exposure to critical organ systems, with particular interest in human and laboratory animal nervous system development.  In association with these activities, Dr. Pleus has conducted a variety of human health risk evaluations of exposures to chemical and biological agents in air, water, food, and soil, as well as risk evaluations relating to consumer products and therapeutic agents.  Chemical agents studied include dioxins, furans, polycyclic aromatic hydrocarbons, metals, volatile and semi-volatile organic solvents, reduced sulfur compounds, exotic chemicals from plutonium production, and inorganic acids and gases.  Biological agents studied include bacteria (e.g., Bacillus anthracis, Salmonella and E. coli) and fungi (e.g., Aspergillus, Penicillium and Stachybotrys).  Consumer products studied include building materials, cleaners, solvents, packaging materials, and medical instruments.  Therapeutic agents studied include agonists and antagonists of the cholinergic, serotinergic, adrenergic systems, as well as opiates.  Dr. Pleus’ work is focused on the application of academic research results to protect human health and resolve public health issues.

Stephen Rennard, M.D., Larson Professor, Internal Medicine-Pulmonary and Critical Care Medicine; Courtesy Professor, Pathology and Microbiology - UNMC.  Chronic obstructive pulmonary disease (COPD) is the major focus of Dr. Rennard’s research.  He maintains active programs both in basic mechanistic studies designed to define the cellular and biochemical processes which lead to altered tissue structure and function in COPD and clinical programs designed to evaluate both the pathophysiology of COPD and therapeutic interventions.  These clinical studies extend to include studies of smoking cessation.  This provides for an integrated program ideally suited to accomplish translational research goals.
    Mechanistic studies focus on the cellular processes underlying repair and remodeling.  Both mesenchymal cells (fibroblasts, smooth muscle cells) and epithelial cells are evaluated in cell culture.  The ability of these cells to modify their surrounding extracellular matrix in response to a variety of pathologic and regulatory stimuli is assessed using cellular and molecular methods.  The role of stem cells in modulating airway repair and remodeling is being evaluated both in vitro and in animal studies. Methods are being evaluated in order to develop techniques to assess remodeling and repair responses in vivo in man.
    Clinical studies include interventional trials evaluating novel therapies for COPD and for smoking cessation.  In addition, the concept of harm reduction is being evaluated both clinically and with respect to the evaluation and validation of outcomes measures.  A variety of methods including bronchoscopy with bronchoalveolar lavage and biopsy, induced sputum and exhaled breath condensate analysis are being used in order to assess the lower respiratory tract, both to evaluate pathophysiologic mechanisms and as outcomes to assess therapeutic interventions.

Eleanor Rogan, Ph.D., Professor, Eppley Institute for Research in Cancer and Allied Diseases; Chair, Department of Environmental, Agricultural and Occupational Health, College of Public Health; Courtesy Professor, Pharmaceutical Sciences, College of Pharmacy - UNMC. The major focus of Dr. Rogan's laboratory is to understand the mechanism of metabolic activation involved in carcinogenesis by polycylic aromatic hydrocarbons (PAH) and catechol estrogen metabolites. Our primary tools in these studies involve analysis of DNA adducts formed in biological systems in vitro and in vivo. The predominant DNA adducts are formed at the N3 and N-7 of adenine and the N-7 of guanine and are lost from the DNA, to generate apurinic sites. We are now studying the relationship between these apurinic sites and oncogenic mutations.  Our research has progressed to studying mechanisms of mis-repair of apurinic sties that may lead to cancer. We hypothesize that apurinic sites generated by loss of catechol estrogen-N3Ade adducts initiate tumor induction in breast, prostate and other human cancers. These studies include not only analysis of estrogen metabolites, conjugates and DNA adducts in human and animal  tissues and fluids, but also determination of the expression of genetic polymorphisms in enzymes that metabolize estrogens.  These multidisciplinary projects include 6 postdoctoral researchers and 3 graduate students. They involve professors from the Eppley Institute at UNMC and a number of other institutions. 

Dojin Ryu, Ph.D., Adjunct Faculty, Food Science & Technology - UN-L.  My current research is focused on using various biological assays to evaluate the fate/toxicity of Fusarium mycotoxins in foods during processes.  The most common toxins produced by the genus Fusarium are deoxynivalenol, zearalenone, moniliformin and fumonisin.  These mycotoxins are known to be very heat stable and cause various adverse effects in animals and humans throughout the world.  Other toxicants that may present in foods, including heterocyclic amines and endocrine disruptors, are also my area of study.  All these toxicants are known to be related to carcinogenesis of animals and possibly humans.  It is therefore important to evaluate biological activities of these toxicants from the dietary sources.

Sam Sanderson, Ph.D., Associate Professor, Clinical Perfusion Education, School of Allied Health Professions; Courtesy Associate Professor, Pharmaceutical Sciences, College of Pharmacy - UNMC. The main focus of Dr. Sanderson's research is to obtain a fuller understanding of the relationships between structure and function of immunologically active peptides. This is approached by the design and synthesis of conformationally constrained versions of these immunoactive peptides with the goal of biasing topochemical features toward specific biological responses, as measured by in vitro and in vivo inflammatory and immunomodulatory assays. Theoretical conformational analyses (energy and dynamic calculations) and high-field NMR are used to evaluate the observed biological properties in terms of structure and topography. A principal objective of this work is to use this structure-activity information as a guide to the design and synthesis of peptide-based therapeutic agents for the treatment of various inflammatory disorders, immune deficiency syndromes, autoimmunity, and cancer.

Polina Shcherbakova, Ph.D., Assistant Professor, Eppley Institute for Research in Cancer and Allied Diseases - UNMC.  Laboratory interests are in the mechanisms controlling genome stability in eukaryotic cells, particularly in the functions of DNA polymerases in DNA replication, repair and chromosome segregation control, and in the impact of environmental genotoxicants on these processes.

Patrick (Pat) Shea, Ph.D., Professor, School of Natural Resources - UNL.  Dr. Shea's research area in the environmental chemistry and toxicology of xenobiotics.  Past research includes the fate and interactions of pesticides and other synthetic organic compounds in soil and water relative to agricultural management and environmental issues.  Current interests include transformation and bioavailability of xenobiotics in soil/sediment and water, remediation and detoxification, and toxicological assessment.  Outreach interests include chemical management for natural resource preservation and agricultural sustainability, and protection of human and environmental health in agricultural and other managed ecosystems.  Many projects are collaborative and interdisciplinary. 

Simon Sherman, Ph.D., Professor, Eppley Institute for Research in Cancer and Allied Diseases; Director, Bioinformatics Shared Resource; Courtesy Associate Professor, Pathology and Microbiology - UNMC.  Dr. Sherman's research interests include: Determination of protein and peptide structures in solution, protein folding, post-translational modifications of proteins, and structure-function relationships in peptides. These activities utilize molecular modeling and computational chemistry techniques to answer biological questions.

Blair Siegfried, Ph.D., Professor, Entomology - UNL.  Dr. Siegfried's research deals with the effects of agricultural pesticides on non-target aquatic organisms that inhabit Nebraska lakes and streams. More specifically, this research is attempting develop an understanding of the biochemical and physiological factors responsible for selective toxicity among freshwater organisms including both invertebrates and algae. Such information is critical to understanding the ecological consequences of pesticide contamination of surface water. Dr. Siegfried is also involved with projects to determine the biochemical and genetic mechanisms of insecticide resistance in insect pest species. Identification of metabolic pathways, target sites and the molecular basis of resistance is essential to the development of rational control strategies that minimize the adverse effects of resistance development and insecticide use. Most of Dr. Siegfried's projects are collaborative and interdisciplinary.

Daniel Snow, Ph.D., Research Associate Professor and Laboratory Director, Water Center, School of Natural Resources - UNL. My research focuses on developing new analytical methods for emerging environmental contaminants like antibiotics, algal toxins, explosives, pharmaceuticals and the products of pesticide degradation.  My goal is to improve our understanding of the impacts of the use of chemicals to the environment and water quality.  I help develop new analytical methods to measure contaminants and their transformation products and apply these methods for research on the environmental fate of these compounds.  The results of this work will help assess the occurrence and environmental fate of these compounds and their potential for impacting living organisms.  I conduct related research on remediation (cleanup) of water contamination and the use of stable and radioactive isotopes as tracers in environmental systems.

Joyce Solheim, Ph.D., Associate Professor, Eppley Institute for Research in Cancer and Allied Diseases - UNMC.  Dr. Solheim's specific research area is immunology, focusing on the cellular immune response to tumors and pathogens and the development of novel immunotherapies for cancer. 

Roy Spalding, Ph.D., Professor, Agronomy & Horticulture - UNL.  Dr. Spalding is principal investigator on several projects designed to further our understanding of the extent, sources, persistence of agrichemicals in our environment, and the remedial alternatives for ground water contaminants. Examples of ongoing projects include: statewide coring analysis and interpretation of the unsaturated zone movement of agrichemicals beneath different agricultural practices; agrichemical contamination of lakes and streams; management effects of improved irrigation and nutrient practices on shallow groundwater quality; enhanced in situ ground water denitrification at municipal well fields; fate and transport of injected herbicides in natural and induced gradient tests; remedial effects of spreading basin recharge; remedial effects of riparian strips along stream borders on surface and ground water quality and effects of spreading basin recharge on ground water quality, nutrient, and analytical methods development for trace concentrations of pesticide degradates, hormones, pharmaceuticals, chlorofluorocarbons, nitrite, and stable isotopes.

Douglas Stack, Ph.D., Associate Professor, Organic Chemistry - UNO.  In order to establish a clear correlation between the formation of estrogen-DNA adducts and the genotoxic properties of estrogen metabolites, we are investigating the underlying chemical mechanism involved when estrogen quinones react with guanine and adenine using computer modeling.  The results of computer modeling studies will be used to design experiments aimed at understanding the sequence of the bond making and bond breaking steps.  Namely, when does cleavage of the glycosidic bond occur?  This information will allow insight into the genotoxic properties of estrogen quinones.

James Takacs, Ph.D., Professor, Chemistry - UNL.  Professor Takacs' research interests are in the area of synthetic organic chemistry. Projects in his research group include the design of new synthetic methods based on catalytic transition metal mediated carbocyclization reactions, the application of these new methods to the total synthesis of natural products, the design and development of enantioselective catalysts, and the design and preparation of new organic optical materials. New transition metal mediated carbon-carbon bond construction reactions, particularly ones that proceed catalytic in metal, are emerging as important new methodologies for organic synthesis. The Takacs group has uncovered several promising new reactions. The iron-catalyzed ene reaction illustrated below is among them. This reaction is being used as a fundamental strategy for the total synthesis of hirsutene, carbocyclin and interesting quinuclidines as illustrated below. In addition to the metal chemistry and synthesis described above the Takacs group is involved in the design of enantioselective lewis acid catalysts for Diels-Alder and ene reactions. These new catalysts are based on transition metal salt coordination complexes with chiral bi-, tri- and tetradentate ligands. Interests in organic materials chemistry are in collaboration with Professors Eckhardt, Wang and Ducharme and focus on the preparation of L-B film forming amphiphiles and nonlinear optical polymers.

Steve Taylor, Ph.D., Professor, Food Science & Technology - UNL.  Dr. Taylor's research interests involve food allergies and allergy-like diseases. He is involved in the development of immunological methods for the detection of allergens, proteins and toxins in food. Dr. Taylor also does research evaluating the safety of foodborne chemicals, both natural and additive.

Susanna Von Essen, M.D., Professor, Internal Medicine-Pulmonary and Critical Care Medicine; Courtesy Professor, Family Medicine and Preventive and Societal Medicine - UNMC.  Dr. Von Essen has long had an interest in the respiratory health of farmers, as well as other rural health issues. Her research focuses on the epidemiology and genetics of occupational lung disease in farmers.  She is Project Director of a five year grant from the National Institute of Environmental Health Sciences which is designed to enhance education in environmental and occupational medicine for primary care providers.

Kay-Uwe Wagner, Ph.D., Associate Professor, Eppley Institute for Research in Cancer and Allied Diseases - UNMC.  Research interests are centered on breast development and tumorigenesis, stem cell biology, and peptide hormone signaling.  In particular, his laboratory has the expertise to develop novel animal models to study the biology of mammary carcinogenesis.