HuGER

Director Bio5, Regents Professor of Plant Sciences (HuGER Associate Director). Dr.
Chandler’s research program focuses on epigenetic mechanisms controlling gene expression with an
emphasis on RNA-directed mechanisms of chromatin control. Her research has revealed that certain RNA-
directed chromatin changes can be transmitted to progeny (a phenomenon known as paramutation) and she is investigating the role this type of regulation may play in certain human diseases, using a number of model
systems, including human cell lines, the mouse and plants. (Vicki's Home Page)

Associate Professor, Division of Epidemiology and Biostatistics, College of Public Health (HuGER Program Faculty). Dr. Chen is also a member of Arizona Cancer Center, Arizona Center on Aging, the Southwest Environmental Health Sciences Center, and the Arizona Arthritis Center. Dr. Chen has been a P.I. or co-I. on a number of research projects related to osteoporosis, body composition, cancer, and aging in different ethnic populations. As an epidemiologist, she has experience with large-scale prospective studies, clinical trials, as well as case-control studies. Dr. Chen is a lead co-I. on the Women's Health Initiative (WHI) in Arizona, and has served as a member of the National Calcium/Vitamin D and Osteoporosis Advisory Committee, and the Special Population Advisory Committee for the WHI over the past 8 years. Dr. Chen’s pending NIH grant (2.6 percentile) titled “Biomarkers and Genetic Factors Related to Sarcopenia in Older Women” will focus on gene and environment interactions for muscle loss in elderly women. (Zhao's Home Page)

Professor, Dept. Cell Biology and Anatomy; Founder and Senior Faculty Advisor to the Genetically Engineered Mouse Models (GEMM) Core Facility; Director, Genetically Engineered Mouse Shared Services (AZCC) (member HuGER Training Faculty). Dr. Doetschman has a multidisciplinary research program that investigates the in vivo functions of the Transforming Growth Factor-β and Fibroblast Growth Factor-2 genes. Four aspects of these multifunctional genes are being presently pursued: autoimmune disease (TGFβ1), colon cancer and lymphoma (TGFβ1), cardiac remodeling (TGFβ1, 2 & 3 and FGF2), and adult cardiac hypertrophy (TGFβ1 and FGF2). The TGFβ1 deficiency that results in a mouse colon cancer model is of special relevance to this training program as there are important interactions between loss of integrity of the colon mucosal epithelium, innate immune alterations, and mucosal/microfloral interactions, the latter two constituting important gene/environment interactions. Of special relevance to the HuGER program are the FGF2 studies in which subtle mutations have been introduced into the FGF2 gene to specifically knockout its multiple, alternative translational start sites to determine the differential functions of these alternatively translated FGF2 protein isoforms at the whole animal level. This work demonstrates that new mouse strains with small sequence polymorphisms can be generated without leaving residual sequences such as selectable marker genes or LoxP or FRT recombination recognition sites in the target gene. Consequently, it is possible to model human polymorphic susceptibility/environmental response variants in mice with no other genetic alteration. These procedures are available to the U of A research community through the GEMM Core Facility. (Tom's Home Page)

Professor Pharmacol/Toxicol; Director, UA Superfund Basic Res. Program, the Southwest Environmental Health Sciences Center, and the US-Mexico Binational Center for Environmental Science and Toxicology (member HuGER Training Faculty). Dr. Gandolfi investigates the effects of sub-cytotoxic doses of arsenic on human proximal tubular ancultures.  Gene array and proteomic techniques are used to profile mechanisms of cell injury. (Jay's Home Page)

Assistant Professor and Director of Epidemiology MPH concentration, College of Public Health and a member of the Southwest Environmental Health Sciences Center (member HuGER Training Faculty). Dr. Guerra’s research interests include, genetic and molecular epidemiology, gene-by-environment interactions in the development and natural history of asthma and COPD, cytokine profiles rhinitis. (Stefano's Home Page)

Assistant Professor of Pharmacology and Toxicology, a member of the Southwest Environmental Health Sciences Center and the Superfund Basic Research Program (HuGER Curriculum co-Coordinator). Dr. Klimecki is a genetic epidemiologist whose research program focuses on environmental and biological factors that modify genetic associations with disease-related phenotypes. His group published the first comprehensive polymorphism catalogs resulting from re-sequencing all genes involved in human arsenic metabolism.  These studies provided the foundation data for Dr. Klimecki’s publication of a polymorphism within the AS3MT gene that strongly associates with urinary monomethyl arsenic levels, a known biomarker of disease risk resulting from arsenic exposure. His group is currently trying to untangle the influence of age and ethnicity in this (now independently replicated) genetic association. Klimecki’s lab is also actively involved in the gene X environment relationships that lead to asthma in children. (Walt's Home Page)

Professor Pharmacology and Toxicology; Director, Southwest Environmental Health Sciences Center (HuGER Training Faculty). Dr. Lau 's research consists of three areas; (i) mechanism of hydroquinone mediated nephrocarcinogenicity (ii) prostanoid mediated cytoprotection, and (iii) proteomic determination of chemical induced post-translational modifications. Specific interests in gene-by-environment interactions focus on the role of the tuberous sclerosis (Tsc-2) tumor suppressor gene product tuberin in modulating the response to DNA damage. Dr. Lau’s laboratory has shown that constitutive renal 8-oxo-guanine-DNA glycosylase (OGG1) expression in rats carrying a germ line mutation in the Tsc-2 gene (Tsc-2EK/+) is lower than in wild type Tsc-2+/+ rats. Moreover, the ability of OGG1 to respond to oxidative DNA damage is impaired in Tsc-2EK/+rats, leading to excessive levels of 8-oxo-deoxyguanosine. The inability to efficiently repair this DNA damage results in more extensive cell death and tissue necrosis in Tsc-2EK/+ rats compared to wild type Tsc-2+/+ rats. The research suggests that tuberin regulates DNA repair function. The haplo-insufficiency for DNA repair function in heterozygous individuals carrying a defective allele of a tumor suppressor gene can result in increased risk for tumor development. Identification of genetic markers in individuals predisposed to tumor development after occupational or environmental exposure to potential carcinogens requires an understanding of how specific genes determine susceptibility to chemical-induced carcinogenesis. Knowledge of the proportion of susceptible individuals in the population and the relative cancer susceptibility of normal and predisposed groups will assist in a more precise estimate of human risk from chemical exposure. (Serrine's Home Page)

Director, Arizona Respiratory Center (HuGER Executive Committee). Dr. Martinez has been the Director of the Arizona Respiratory Center since 1996. Under Dr. Martinez' direction, the Arizona Respiratory Center has fostered the integrated work of clinicians, epidemiologists, immunologists, pharmacologists, molecular and cellular biologists, and population geneticists, all centered around efforts to elucidate the mechanisms that contribute to these complex respiratory diseases, with the goal of developing new ways to prevent and treat them. Dr. Martinez’s own research focuses on the natural history and risk factors for asthma and other wheezing disorders from birth to early adult life. He is a member of the FDA Pulmonary-Allergy Drugs Advisory ComLung, the Southwest Environmental Health Sciences Center, and the Blood Institute since 1999. (Fernando's Home Page)

Professor and Head, Dept. Pharmacology and Toxicology and a member of the Southwest Environmental Health Sciences Center (P.I. and Director of the HuGER Training Program). Dr. Monks’ research program focuses on the molecular basis of reactive oxygen species- (ROS) induced cell death. Mechanisms of cell death are usually classified into two pathways, apoptosis and necrosis. The American Society of Toxicologic Pathologists uses the term oncosis, with its root meaning of “swelling,” as the alternate descriptor of cell death occurring by non-apoptotic pathways. Necrosis more accurately describes the consequences of oncotic cell death, usually the death of a large number of cells resulting in moderate to severe tissue injury. Oncotic cell death typically occurs in response to toxic injury induced by chemical exposure and ROS. ROS also contribute to a variety of human diseases. Understanding factors that regulate the cellular stress response to ROS and the molecular mechanisms by which they interact with cellular constituents, and the consequences of such interactions, are important fundamental goals of biomedical research. Responses to stress that usually result in oncotic cell death (and tissue necrosis) may be manipulated, at the genetic and pharmacological level, to produce a potentially favorable (survivable) tissue response. Basic knowledge of the mechanisms by which ROS induce cell death may yield strategies for clinical interventions in pathologies in which ROS play a prominent role. The laboratory is investigating the cellular and molecular mechanisms by which ROS induce both apoptotic and oncotic/necrotic cell death. (Terrence's Home Page)

Professor of Ecology & Evolutionary Biology, Director NSF-IGERT Program in Genomics (member HuGER Training Faculty). Dr. Nachman and the members of his laboratory study mouse and human population genetics and genomics. The laboratory focuses on the genetic basis of complex traits, the genetic underpinnings of specific adaptations, and the genetic basis of speciation. For example, the group has begun developing wild mice as models for genetic association studies of traits with complex gene- environment interactions, including diet-induced obesity and metabolic syndrome. Studies on the genetic basis of adaptation include research on melanism in rodents and efforts to identify regions of the human genome that have recently experienced positive natural selection, including genes associated with innate immunity (in collaboration with D. Vercelli and W. Klimecki). In studies of speciation, the Nachman laboratory has mapped genomic regions contributing to reproductive isolation between closely related species of house mice. Construction of congenic strains of mice is enabling the functional analysis of specific genes and mutations. Related work seeks to understand the genetic basis of differences in male fertility within natural populations of mice as well as the molecular evolution of genes involved in reproduction. (Michael's Home Page)
 

Professor of Mathematics; Professor of Public Health; Director, Graduate Interdisciplinary Program (GIDP) in Statistics (HuGER Executive Committee).  Dr. Piegorsch studies modeling and analysis for environmental data, with emphasis on environmental hazards and risk assessment.  He coordinates these interests with his research in environmental toxicology, emphasizing mutagenesis and genotoxicology; geo-spatially referenced disaster informatics; multiple comparisons; and the historical development of statistical thought as prompted by problems in the biological and environmental sciences.  He currently leads a research team developing statistical methods for estimating benchmark dose markers from environmental hazard analyses, for use in quantitative risk assessment. This research is funded by the U.S. National Cancer Institute and the U.S. EPA. He also has constructed statistical models for data from transgenic bio-technologies, developed guidelines for the design of bioassays in select transgenic animal systems, and has proposed retrospective designs for analyzing gene-environment and gene-nutrient interactions in human population studies. (Walter's Home Page)

Thomas R Brown Chair in Bioengineering, and Professor of Electrical and Computer Engineering (HuGER TG Trainee Advisor). Dr. Powers’ current research efforts involve the detection and identification of microbial [bacteria, viruses, fungi, toxins] contamination with applications to foods/water/air quality, sterilization/decontamination, medical diagnostics, homeland security, and the search for life in extreme environments [as surrogates for the moon, Mars, and Europa].  As part of this effort, Dr. Powers’ laboratory designs, builds, and test optical-based instruments for detection of microbes as well as receptor technology for capture and identification of the microbial population even at very low numbers. Dr. Powers has participated in NIH Training Grants whilst a member of the Technical Staff at AT&T Bell Labs. at the Univ. of Pennsylvania Medical School and at Princeton University [as a Visiting Fellow]. Both training programs produced several PhD students who are now leaders in their respective fields and are Directors of both industrial and academic research laboratories. At Utah State University, Dr. Powers was the P.I. of an NIH Research Resource Grant which had a training component for engineers and post-doctoral fellows in the biosciences. This program produced several highly qualified scientists who understood both the bioengineering aspects of developing novel methodology and instrumentation for the biosciences.  (Linda's Home Page)

Associate Professor of Agriculture and Biosystems Engineering, Chemical and  Environmental Engineering, Materials Science and Engineering, (HuGER Curriculum co-Coordinator). Dr. Riley is also a member of the GIDP in Biomedical Engineering, the Southwest Environmental Health Sciences Center, and a member of the BIO5 Institute. His laboratory provides engineering solutions to address challenges in health, environment, and agriculture through developing sensors and monitoring technologies. Recent projects include development of cell based spectroscopic sensing to quantity the potential health impact of airborne particulates, viruses, and pesticides. Dr. Riley has also developed a simple device (RediRipe) to evaluate fruit maturation by providing a simple color change in response to ethylene released.  (Mark's Home Page)

Dept. Immunobiology, Head, Microbial Pathogenesis Program (member HuGER Training Faculty). Dr. So’s research is anchored at the interface of immunology and microbiology, disciplines that are key to our understanding of basic life processes and to our quest to improve human health. One has only to consider some of the most important public health problems to realize the relevance of these two fields to modern medicine. The disease state, be it cancer or of infectious origin, is the result of the complex interplay of the host and its environment, and Dr. So’s laboratory studies various aspects of this complex web, using techniques and approaches from many disciplines, including molecular biology, biochemistry, cell biology and genetics. Dr. So effectively couples research with graduate training, having served as the P.I. on two NIfunded training grants, the most recent being “Interactions at the Microbe/Host Interface” from 1995-2005.  (Magdalene's Home Page)

Professor, Dept. of Cell Biology & Anatomy. Asst. Director Arizona Respiratory Center,
Functional Genomics Laboratory (HuGER Seminar Coordinator). The central theme of the Functional
Genomics laboratory is the characterization of the mechanisms through which natural variation in immune
genes contributes to the pathogenesis of complex diseases, with special emphasis on respiratory disorders
such as allergic inflammation and asthma. The approach taken is to assess the impact of genetic
polymorphisms on the function and regulation of specific genes, focusing on those shown to be strongly
associated with allergic inflammation and asthma phenotypes. Genes currently under study are IL13, GATA3, TLR2 and CD14. The laboratory evaluates how coding region polymorphisms result in the expression of proteins with altered biological properties. Complementary studies test the effect of genetic variation on transcriptional regulation and mRNA stability. A combination of biochemical purification and functional analysis is used to identify transcription factors that bind differentially to polymorphic alleles. The laboratory is also investigating the basic epigenetic mechanisms that regulate gene expression and the elements involved in gene regulation. More recently, the laboratory initiated genome-wide analyses of DNA methylation and gene expression patterns in relation to specific environmental exposures and genotypes. This work, performed in collaboration with the Genomics Shared Service of the SWEHSC, relies on comprehensive genetic databases generated at the Arizona Respiratory Center by re-sequencing innate and adaptive immunity genes in a large panel of reference DNA samples of known ethnicity, as well as in populations of defined allergic disease phenotypes. The next stage of the work, currently in advanced state of development, involves the generation of BAC transgenic mice to model alternative haplotypes of the genes of interest and to study their expression and phenotypic correlates in vivo. The ultimate goal of the Functional Genomics Laboratory is to establish a new paradigm merging analysis of genetic and environmental determinants of disease, and functional studies and patient phenotypes to understand the causes of disease and predict responsiveness to specific treatments. (Donata's Home Page)

Professor and Associate Head of Ecology and Evolutionary Biology; Adjunct Professor of
Animal Sciences, Epidemiology and Biostatistics, Molecular and Cellular Biology, and Plant Sciences (HuGER training faculty). Dr. Walsh is a member of Bio5 and founding Chair of the GIDP in Statistics and also member of the GIDP programs in Applied Mathematics, Genetics (former Chair), and Insect Science. Dr. Walsh’s research focus is statistical and population genetics/genomics, especially the genetics of complex traits.
Relevant to this proposal is his strong interest in the use of mixed-model approaches for the detection and analysis of genotype-environment interactions. He is co-author (with Michael Lynch) of the leading graduate textbook on Quantitative Genetics (Genetic and Analysis of Complex Traits) and routinely teaches international graduate/post graduate short courses on various topics in statistical/quantitative genetics (including ~12 short courses in Aarhus, Seoul, Copenhagen, Helsinki, Faro, Melbourne, Birmingham, Seattle, San Francisco, and Raleigh in the last 5 years). (Bruce's Home Page)