Dr. Serrine Lau was recruited from the University of Texas at Austin to serve as the new Director of the Southwest Environmental Health Sciences Center, effective September 1, 2003. Dr. A. Jay Gandolfi served as Interim Director from June 1 to August 31, 2003 following Dr. Daniel Liebler's departure to Vanderbilt University. The Director has primary responsibility for communicating with NIEHS staff on all organizational and financial matters of the SWEHSC, including the Administrative Core. The Director also chairs the Internal Advisory Board (IAB), and supervises the activities of the Administrative Associate and Accountant.

Over the past four years Dr. Clark Lantz has served as the Deputy Director. His duties are to assume administrative responsibilities in the absence of the Director, and to administer the Pilot Projects Program and the Seminar Series.

The Directors of the Research Cores and the Facility Cores are responsible for the effective management, and for providing scientific leadership for their Cores. The main functions of the Director and Deputy Director are to ensure that these units are interactive, productive, and synergistic.
-Top-

Director: Serrine S. Lau, Ph.D.
Serrine S. Lau, received her Ph.D. in Pharmacology from the University of Michigan and completed her postdoctoral training at NIH. She was recruited from the University of Texas at Austin, where she held the endowed Johnson & Johnson Professorship in Pharmacology and Toxicology, in the College of Pharmacy. She was approved to lead the SWEHSC by NIEHS effective September 1, 2003. From April 1, 1995 to August 31, 2003, Dr. Lau served as the Director of the Analytical Instrumentation Facility Core within the Center for Research on Environmental Disease, a NIEHS Center jointly awarded to the University of Texas M.D. Anderson Cancer Center and the University of Texas at Austin. While at the University of Texas at Austin Dr. Lau also served as the Director of the NIEHS-funded Toxicology Training Program, and the NIEHS-funded Minority Undergraduate Training Grant. Dr. Lau plays an active leadership role in a number of professional organizations serving the field toxicology and the environmental health sciences. She has served on numerous elected and appointed committees. Dr. Lau has been especially active within the SOT; serving as an elected member of the Education Committee (1990-1993); councilor for the Gulf Coast Regional Chapter of SOT (GCSOT, 1994-1996); appointed to the Awards Committee (1994-1996); elected Secretary/Treasurer of the Mechanisms Specialty Section (1996-1998); elected Secretary/Vice President Elect/President/Past President of GCSOT (1997-2003); elected VP-Elect/VP/President of the Mechanisms Specialty section (2002-2005) appointed to the Board of Publications (1999-2002); and recently elected to the SOT Council (2002-2004). Dr. Lau was appointed to the NIH Pharmacology Study Section grant review panel (1992-1996); served as an elected member of the Drug Metabolism Division Executive Committee, a section of the American Society of Pharmacology and Experimental Therapeutics (1992-1995); and she was elected to the Council of the International Society for the Study of Xenobiotics (1998-2000). Dr. Lau served as a member of an Advisory Committee for the NIH Center for Scientific Review on the organization and management of peer review within the Cardiovascular Sciences Integrated Review Group (2002), as a member of the Digestive Sciences IRG Study Section Boundaries Team for Study Section reorganization (2002), and was recently appointed to the Committee on Emerging Issues and Data on Environmental Contaminants, an Advisory Committee to the National Research Council of the National Academy of Sciences (2002-present). These responsibilities and commitments provide Dr. Lau with the necessary insight to lead a productive and vibrant NIEHS center.

In addition to her administrative responsibilities, Dr. Lau maintains a highly productive and visible research program. Dr. Lau has been continuously funded by the NIH since 1987, and is currently the recipient of two NIH grants (with a third pending review). In addition Dr. Lau is a co-PI on a grant from the Philip Morris External Research Program. Dr. Lau is a recognized expert in the general field of molecular toxicology, with significant contributions in the areas of drug metabolism, mechanisms of chemical-induced toxicities, and renal toxicology and nephrocarcinogenesis. Her most recent area of interest is in proteomics, and she has a rapidly expanding research effort in this endeavor. Dr. Lau has over 120 publications and over 170 published abstracts, including several important invited review articles. Dr. Lau has (or is currently) mentored 14 predoctoral and 9 postdoctoral students each of whom were actively recruited by academia, government, or industry, and many have since established productive careers in toxicology. Dr. Lau is also an active and accomplished participant in both graduate and undergraduate teaching, having coordinated and developed several courses while at the University of Texas at Austin.
-Top-

Deputy Director: R. Clark Lantz, Ph.D.
R. Clark Lantz received his Ph.D. in Physiology from West Virginia University and completed his postdoctoral training at Rockefeller University and Emory University. He joined the faculty in the Department of Cell Biology and Anatomy at the University of Arizona in 1987. He is currently Professor and Associate Head of Cell Biology and Anatomy and a member of the Arizona Cancer Center. He maintains active research projects that examine the pulmonary toxicity of arsenic and uranium. He has served as the Director of the Cellular Imaging Facility Core (previously the Experimental Pathology Facility Core) of the SWEHSC since its inception in 1994 and currently heads the Pulmonary Injury Research Core. He also serves as the Chair of the University wide Biotechnology Imaging Users Committee, which oversees the Shared Imaging Equipment on campus. He is a member of SOT and is currently the President of the Mountain West Regional Chapter of SOT. He also serves on the Public Affairs Committee of the American Association of Anatomists. He has served as Deputy Director of the SWEHSC since 2000 and is responsible for administering the Pilot Projects Program and the Seminar Series.
-Top-

Administrative Consultant: I. Glenn Sipes, Ph.D.
Dr. I. Glenn Sipes will serve as an administrative and scientific consultant. Dr. Sipes developed the proposal submitted to the Arizona Board of Regents for the establishment of the Center for Toxicology. Upon its approval he served as Founding Director. A key goal of the Center for Toxicology was to obtain NIEHS Center status. That was achieved in 1994 when the Southwest Environmental Health Sciences Center was funded by NIEHS with Dr. Sipes as the first director. After the successful competitive renewal of the SWEHSC, Dr. Sipes resigned as director to serve as Head of the Department of Pharmacology in the College of Medicine. Dr. Sipes’ talents and experience have served toxicology well at the University of Arizona. In addition Dr. Sipes serves as a consultant to WHO and reviewer for EPA and other agencies, thus keeps abreast of safety/risk assessment issues and the need for a translational focus. He will continue to be a resource to SWEHSC.
-Top-

Administrative Associate: Susanna Brodie.
Ms. Brodie has served as the Administrative Associate for the SWEHSC since 1999. She manages the day-to day activities of the Center, provides assistance to all units within the SWEHSC, and coordinates Center activities with staff at NIEHS and at other NIEHS centers. Her responsibilities include the coordination of information retrieval and dissemination within the SWEHSC, preparation of reports, meetings and activities of the Internal and External Advisory Committees, the SWEHSC Science Fair, arrangements for SWEHSC-sponsored scientific workshops, travel, room scheduling and other arrangements for SWEHSC seminar speakers, production of the SWEHSC newsletter, and all business and financial operations associated with the SWEHSC. In addition, Ms. Brodie maintains a database of all SWEHSC members’ research support and publications, processes purchase requisitions for the SWEHSC, assists the Director, Deputy Director, Research Core Directors and Facility Core Directors in assembling information for reports and research summaries, and assists the Director and Deputy Director in writing reports and preparing research summaries.
-Top-

Accountant, Senior: Karla Nunez
Ms. Nunez joined the Center for Toxicology in 2002 to jointly act as the Accountant for both the NIEHS supported SWEHSC and the Superfund Program. She joined us after several years of accounting experience in engineering and business on the main campus. Due to the explosion of research activities in the College of Pharmacy over the past 5 years, it became evident that the NIEHS programs needed a dedicated accountant. In many ways Ms. Nunez acts as a departmental business manager. She oversees the processing of purchase orders, sets up all accounts, oversees account expenditures, sets up contracts, sets up instrument leasing, links to accountants and business managers in the SWEHSC member’s departments, remains trained and updated in all the financial procedures of the University, and handles all “overflow” postdoctoral, staff, and laboratory personnel hiring. Ms. Nunez provides weekly financial reports to the Program Director and detailed quarterly reports to all the Service Core directors. Weekly and Quarterly review of the reports resolves many management problems.
-Top-

Advisory Boards

Internal Advisory Board (IAB)

Key to the functioning of the SWEHSC is the Internal Advisory Board (IAB). During the past five years the IAB has served a number of roles, including oversight, evaluation, management, and direction. The hard work and dedication of the IAB greatly assists the Director in leading the activities of the SWEHSC. The constitution of the IAB includes the Directors of the various Research and Facility Cores, and an at-large representative of Center investigators. The Center Director serves as the chair of the board. The composition of the IAB is designed to provide an administrative voice for each Research Core, to promote integration and coordination among Research Cores, and to ensure that the Facility Cores are continually meeting the needs of Center Investigators. The IAB convenes at 2-3 month intervals. By meeting on a routine basis, the IAB has ample opportunity to assist the Center Director in making scientific and administrative decisions, and in the allocation of resources.

The IAB is also responsible for funding decisions following the peer review of Pilot Project applications. A continuing item on the Board agenda is the evaluation and assessment of the Research Cores, Facility Cores, Administrative Core, and COEP. The IAB interacts with the various Core Directors and their staff to: review activities, discuss strengths and weaknesses, and set direction for future activities. As a result of such evaluations, the IAB acts in an informed manner to affect change. Key changes that have resulted from such oversight include the reorganization of the Research Cores; appointment and retention of SWEHSC investigators; increase in funding levels for Pilot Projects, and ultimately a redefinition of the role of the IAB.

In future years IAB will be asked to assist the Director in making strategic scientific and administrative decisions, and in formally evaluating the performance of key elements of the Center (i.e. serving as an internal "science advisory board"). By assuming this charge, the IAB can assist in directing the future scientific direction of the Center. The IAB may appoint “ad hoc” members on occasion to allow for greater scientific input in the decision making process. The IAB will continue to evaluate the various programs of the SWEHSC and provide its evaluations to the External Advisory Board. The IAB will be particularly attentive to the progress of the Research Cores with respect to promoting interdisciplinary/collaborative interactions and to the submission of joint grant applications. Progress of the Research Cores will in part be determined by joint publication of members, new pilot collaborative grants, and by the submission and funding of interdisciplinary grants, especially Program Project grants. It should be noted that the COEP formalized its own IAB and EAB as described in the COEP write-up.

External Advisory Board (EAB)
The EAB provides an independent assessment of SWEHSC programs and progress, and provides insight for future direction. Members of the EAB are all distinguished scientists, selected for their excellence in research, their ability to add expertise to various Research Cores or Facility Cores, and their familiarity with the research activities of SWEHSC investigators. In addition, EAB members have considerable experience in program administration, grant and manuscript review, and multidisciplinary interactions. The EAB appreciate how collaborative, interdisciplinary efforts can lead to major scientific advances. Changes in the membership of the EAB since the last application reflect changes in the direction and focus of Research and Facility Cores during that time.

• Reorganized the Research Cores to better reflect their biological/toxicological focus and utilize the well developed methodological capacity in cell /tissue imaging, proteomics and genomics in advancing research inquiry on important toxicological and environment health issues.
• Provided increased investigator access and financial benefit to state-of-the art methods through the Facility Cores.
• Encouraged the COEP to continue utilizing existing resources at the University of Arizona to enhance its activities and to seek additional resources through other programs offered by NIEHS. The COEP is encouraged to continue and expand on activities involving established partnerships with area schools, tribal nations, water districts and other communities to further its mission and outreach function. The EAB recommended the establishment of advisory boards to evaluate the outreach activities. As such COEP will bring together two new Advisory Boards. These new Boards are an Internal Advisory Board (IAB) of Center Scientists, to review the scientific content of COEP materials and programs, and a Community Advisory Board (CAB) of community members and COEP partners, to advise COEP about local issues and projects that will promote Center and COEP priorities.
• Expand on the partnership with the Arizona Cancer Center so that environmental factors associated with cancer etiology can be better explored, as well as to share and develop resources that can better serve the investigators of both Centers. The Proteomics Facility Core, Genomics Facility Core, Synthetic Chemistry Facility Core and the proposed Bioinformatics Facility Core (see below) continue to be jointly sponsored by both centers.
• Established more formal relationships with the Colleges of Public Health, Medicine and Nursing, to better translate mechanistic findings into human health applications.
• Recommended changes to the Facility Cores. The EAB recommends that the SWEHSC better envelop the strong bioinformatics/biocomputational capabilities that exist on the University of Arizona campus, thereby strengthening its linkages to these resources. Dr. David Mount was asked to direct this core as a co-sponsored core with the Arizona Cancer Center, which will better serve SWEHSC investigators that are working on proteomic, genomic, and imaging research problems.
• In addition, EAB endorsed the proposal of developing a new “Gene Delivery Facility Core” to better serve the need of SWEHSC members.
• Continue to utilize the Pilot Projects Program to recruit and encourage new investigators into environmental research and eventually become members of SWEHSC.

EAB Members:

Curtis Omiecinski Ph.D. (chair)
The research in Dr. Omiecinski’s laboratory is focused on the molecular biology of mammalian biotransformation. Variability in the expression of biotransformation activities appears to substantially impact individual responsiveness to both pharmaceutical and toxicant exposures. One line of laboratory endeavor relates to the study of the regulatory mechanisms responsible for controlling the expression of the biotransformation enzymes. Recently, a variety of ligand-activated nuclear receptors have been characterized that serve as “xenosensors” in mammalian cells and function as transcriptional activators of a variety of genes, including the cytochrome P450s. The P450s are key components of the drug and chemical metabolism pathway. Phenobarbital (PB) is an example of clinical compound that produces marked activation of the expression of several P450 genes, in a process that is regulated by the constitutive androstane receptor (CAR). Dr. Omiecinski’s laboratory studies signaling cascades activated by inducer exposures and nuclear events dictating altered DNA-protein and protein-protein interactions associated with the induction process. Experimental models in use include primary hepatocyte cultures and transgenic mouse systems. Investigations are underway examining the transcriptional activation processes involved in gene induction, such as the interactions of nuclear receptors with core DNA enhancer elements and the associated network of nuclear co-activator and co-repressor proteins. Dr. Omiecinski is very interested in determining genetic variation in nuclear receptor structure that may impact important clinical and toxicological outcomes.

A parallel investigation in Dr. Omiecinski’s laboratory involves the characterization of the human epoxide hydrolases, including their structure, regulation and genetic variability. These enzymes, like the P450s, also function to biotransform a variety of drug and toxic substances, typically acting upon epoxide intermediates produced by P450 reactions. Epoxide hydrolase often functions to render the epoxides less chemically reactive. Two forms of human hydrolase are being studied, the microsomal epoxide hydrolase and the soluble epoxide hydrolase. The microsomal enzyme is active against a broad array of xenobiotic chemicals whereas the soluble enzyme principally participates in the metabolism of endogenous substances such as the arachidonate derivates, the epoxyeicosotrienoic acids. The epoxide hydrolase research program involves characterization of genetic variation, structure-function relationships, and tissue-specific regulation of their expression.
-Top-

M.W. Anders, Ph.D.
Dr. Anders’ research is to understand the mechanisms by which drugs and chemicals produce cell and organ toxicity and the role of cellular cytoprotective mechanisms in modulating toxicity. The toxicity of most organic chemicals is associated with their biotransformation to reactive, electrophilic metabolites or to stable, but toxic, metabolites that cause cell damage. He is particularly interested in three aspects of chemical bioactivation: one, what is the chemical nature of the metabolites formed; two, what enzymes are involved in the formation of toxic metabolites; and, three, how is the formation of toxic metabolites coupled to the production of cell damage? Several approaches are used to investigate the bioactivation of chemicals. Reaction mechanism studies are conducted to understand the metabolic pathways involved and to gain insight into the nature of reactive intermediates, which may be too short-lived to be isolated. Studies on the perturbation of cellular glutathione homeostasis are employed to examine the relationships between toxic metabolite formation and cell damage. Several techniques are used, including mass spectrometry and nuclear magnetic resonance spectroscopy, to identify metabolites, immunohistochemistry to map the distribution of bioactivation and cytoprotective pathways, and development of transfected cell lines to study drug-induced cell damage. Present studies are focused on the glutathione-dependent bioactivation of halogenated alkenes and haloacids, on the enzymology and regulation of glutathione biosynthesis, and on the enzymology of the mercapturic acid pathway, including cytosolic and microsomal glutathione transferases, cysteine S-conjugate N-acetyltransferase, and acylase. New studies on the selective targeting of cytoprotective chemicals to cellular organelles, i.e., mitochondria, have just begun.
-Top-

Thomas Kensler, Ph.D.
Research interests in Dr. Kensler’s laboratory focus on the biochemical and molecular mechanisms involved in the induction of cancer by chemicals to serve as a basis for the prevention, interruption or reversal of these processes in man. One of the major mechanisms of chemical protection against carcinogenesis, mutagenesis and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S-transferases, UDP-glucuronosyl transferases and NAD(P)H:quinone reductase. Furthermore, animal studies indicate that induction of phase 2 enzymes is a sufficient condition for obtaining chemoprevention and can be achieved in many target tissues by administering any of a diverse array of naturally-occurring and synthetic chemical agents. Dr. Kensler’s work utilizes animal and cell culture models to elucidate mechanisms of inhibition of aflatoxin hepatocarcinogenesis by dithiolethiones such as oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithole-3-thione]. While induction of glutathione S-transferases clearly play an important role in chemoprevention of aflatoxin hepatocarcinogenesis, ongoing studies are seeking to identify additional induced genes. cDNAs for several novel as well as unexpected genes have been isolated, several of which are involved in attenuating oxidative stress and inflammation. Their contributions to protection against carcinogenesis are under investigation. Studies are also underway to elucidate the role of Nrf2 and other transcription factors in mediating enzyme induction by chemopreventive agents.

A practical goal of Dr. Kensler’s research has been to develop the tools to test the hypothesis that enzyme induction is a useful strategy for chemoprevention in humans. Hepatocellular carcinoma is the leading cause of cancer death in parts of Asia and Africa and may relate to hepatitis B virus infection and aflatoxin ingestion. Longitudinal surveys and prospective case-control studies in Qidong, P.R. China demonstrate consistent exposure of individuals in this region to aflatoxins and indicate a prime role for aflatoxin in the etiology of liver cancer, respectively. As a consequence, Dr. Kensler is conducting clinical chemoprevention trials of oltipraz and other agents in Qidong. The initial randomized, placebo-controlled intervention of oltipraz demonstrated an increased excretion of aflatoxin-mercapturic acid, a derivative of the aflatoxin-glutathione conjugate, in the urine of participants receiving oltipraz. This study highlights the general feasibility of inducing phase 2 enzymes in humans. Follow-up trials are assessing whether protective alterations in aflatoxin metabolism can be sustained for extended periods of time and whether diminished incidence of liver cancer can be achieved in this high-risk population.
-Top-

Charles Plopper, Ph.D.
Dr. Plopper’s current research interests are in the following areas: Pulmonary cell biology; experimental lung pathology; cellular toxicology; pulmonary developmental biology; regulation of cytochrme P-450 monooxygenase system; transmission and scanning electron microscopy; autoradiography; immunocytochemistry; cytochemistry; morphometry and cell culture.
-Top-

John DiGiovanni, Ph.D.
Research interests in Dr. DiGiovanni’s laboratory focus on four major areas: i) identifying critical targets and mechanisms involved in the initiation and promotion stages of chemical carcinogenesis; ii) identification of genetic determinants of susceptibility to chemically-induced cancer; iii) exploring novel chemoprevention strategies for inhibiting chemical carcinogenesis; and iv) collaborative molecular epidemiologic studies on the relationship between cigarette smoking, DNA adduct levels, genetic polymorphisms and susceptibility to lung and other tobacco-related cancers in specific human populations.

Research in the area of mechanisms of tumor initiation involves studying polycyclic aromatic hydrocarbon (PAH), which are ubiquitous environmental pollutants produced in cigarette smoke, automobile exhaust, and other combustion associated processes. These studies are providing information, at the molecular level, about mechanisms whereby PAH carcinogens induce the early events in cancer. Current and future work in this area involves studies to determine the type(s) of DNA damage produced by environmental PAH carcinogens, the relationship to specific mutations in cancers linked to exposure to these carcinogens, and the role of DNA repair.

Current research in understanding mechanism(s) of tumor promotion is elucidating growth factor signaling pathways involved in this process using the mouse skin carcinogenesis model system. Dr. DiGiovanni’s laboratory has recently developed several transgenic models based on overexpression of IGF-1, erbB2, and c-src in skin epidermis. Ultimately, these studies will lead to the identification of new targets and model systems for chemoprevention/intervention studies.

In the area of chemoprevention research, Dr. DiGiovanni’s laboratory is currently examining naturally occurring coumarins that may have potential as chemopreventive agents. These compounds are ubiquitous in higher plants and are particularly rich in citrus oils and certain vegetables, such as cilantro and celery. The potential anticarginogenic properties of these natural coumarin derivatives are being examined in preclinical studies using the multistage model of mouse skin tumorigenesis with promising results. These chemicals act as blocking agents, preventing carcinogen-induced DNA damage. Since humans ingest these compounds regularly, they may hold promise as potential chemopreventive agents in man.
-Top-

Richard Caprioli, Ph.D.
Richard M. Caprioli is the Stanley Cohen Professor of Biochemistry and Director of the Mass Spectrometry Research Center at Vanderbilt University School of Medicine. He is also currently Professor in the Departments of Chemistry and Pharmacology at Vanderbilt.

Professor Caprioli is interested in the use of mass spectrometry for the analysis of compounds in biological systems. Current work includes the use of electrospray and laser desorption ionization methods with biological tissues and samples. Applications have focused on the development of this instrumentation and associated methodologies to achieve ultra-high sensitivity detection of endogenous compounds (e.g., neuropeptides) in live animal systems. A major focus is the use of MALDI MS for molecular image analysis of biological samples. He has published over 300 scientific papers, including three books. He is currently co-editing a volume Encyclopedia of Mass Spectrometry.
-Top-