2009 Award Recipients

Russell S. Thomas

Russell S. Thomas, M.S., Ph.D., is recognized by the Society of Toxicology for outstanding contributions in bringing high data content, high throughput transformational research approaches to toxicology and applying these methods in a risk assessment context. Dr. Thomas, Director of the Center of Genomic Biology and Bioinformatics, The Hamner Institutes of Health Sciences, received his Ph.D. degree in Toxicology from Colorado State University in 1997 with Dr. Raymond Yang for research modeling the pharmacokinetics and modes of action of hepatic carcinogens. His interest then shifted to molecular biology, genomics, and high-throughput screening during his postdoctoral period and early career work in the biotech field.

Over the past five years, Dr. Thomas has pursued a broad research program in genomic biology, bioinformatics, and risk assessment to understand the complexities of responses of biological systems to chemical stressors. His high data content, frequently robot-assisted methodologies query underlying biology in much greater depth and breadth to examine the consequences of perturbations of biology by environmental agents. These tools allow much more rapid survey of possible targets of toxicity and provide greater detail about the signaling pathways related to target pathways and their dose response characteristics. For most of his recent publications, Dr. Thomas has had to develop co-ordinate bioinformatics tools to analyze the large quantity of data obtained from these technologies. The contributions in developing these informantic tools are as important as the research results themselves. Key contributions include tools to identify toxicologically predictive gene sets, genome wide functional profiling of the AP-1 signaling pathway, functional mapping of the NF?-B signaling pathway with full-length c-NA and si-RNA gene libraries to identify novel modulators and describe systems level pathway control, and applying benchmark dose modeling of genomic data to identify doses at which different cellular processes are altered. His paper on benchmark dose modeling with genomic data was recognized as the best paper related to the scientific basis of risk assessment for 2008. In recognition of the broad scope and transformational character of his early career research contributions, the Society of Toxicology is pleased to present the 2009 Achievement Award to Dr. Russell S.Thomas.

Michael Bolger

Michael Bolger, Ph.D., DABT, receives the 2009 Arnold J. Lehman Award. He is an internationally recognized expert in the toxicology and safety/risk assessment of food-borne anthropogenic and naturally-derived chemical contaminants in food. These would include elemental contaminants, mycotoxins, seafood toxins, organic contaminants like dioxin-like contaminants, phenolic compounds, and mixtures of chemicals. As such, he has provided critical leadership and advice on important regulatory decisions on tolerable levels of chemical contaminants and natural toxicants in food. Dr. Bolger’s multidisciplinary background in physiology, pharmacology,
and toxicology allows him to provide scientific evaluations of highly complex data and insightful conclusions on hazards of these chemical contaminants.

He is highly sought as a member for U.S. government and international review panels such as the Interagency Risk Assessment Workgroup for Dioxin/Furans, the CDC Advisory Committee on Childhood Lead Poisoning, the NOAA Expert Toxicological Committee on Oil Contamination of Seafood, the WHO Task Group on Methyl Mercury, the Interagency Methyl Mercury Workshop, the EPA Dioxin/Furan Reassessment Peer-Review Group, and on many joint expert committees of the World Health Organization (WHO) on food-borne environmental contaminants. He is currently serving in a second five-year term as a WHO designated food safety expert and as a member of the Expert Advisory Panel on Food Safety and the Foodborne Disease Burden Epidemiology Reference Group of the World Health Organization. He has also contributed a number of significant publications that support FDA regulations. Dr. Bolger is well-published, credible in his individual risk assessments, and forceful yet polite in his arguments. He is also purposeful, determined, and untiring in his efforts to incorporate the best toxicology information into individual chemical risk assessments. He has moved the field of risk assessment forward though innovative thinking and principled risk assessment practice. We are delighted to have Dr. Michael Bolger as the Arnold J. Lehman awardee for 2009.

Lance R. Pohl

Lance R. Pohl, Pharm.D., Ph.D., is the recipient of the 2009 Distinguished Toxicology Scholar Award. Dr. Pohl is Chief of the Section on Molecular and Cellular Toxicology in the Laboratory of Molecular Immunology at the National Heart, Lung, and Blood Institute. For more than 30 years, he has been a leader in the field of drug toxicity. His seminal work on the anesthetic halothane established the association between biotransformation, covalent adduct formation and immune response with idiosyncratic hepatotoxicity. His laboratory has also made several other major contributions to the field of toxicology, including the development of innovative techniques for identifying highly reactive and toxic metabolites of drugs and other xenobiotics that are produced by cytochrome P450s and other hemoproteins and the first design and use of specific antibodies for exploring the identity and toxicologic consequences of in vivo protein adducts of hepatotoxic drug metabolites. In more recent years, he and his colleagues have used animal models to identify numerous cytokines and other factors that determine susceptibility to drug-induced liver injury. For example, Dr. Pohl and colleagues discovered that Kupffer cells can protect against drug-induced liver injury, while endogenous glucocorticoids can potentiate it, and both of these factors may have a role in preventing drug-protein adducts formed in the liver from causing allergic reactions by inducing immunological tolerance. His passion for discovery is reflected in those who have trained in his laboratory, many of whom have gone on to distinguished scientific careers of their own. Dr. Pohl’s professional record is the epitome of a career of distinguished scholarship in toxicology, and he is a highly deserving recipient of this 2009 Distinguished Toxicology Scholar Award.

Janice E. Chambers

Janice Chambers, Ph.D., has contributed broadly to the successful development of toxicology education and training programs. After receiving a B.S. in Biology at the University of San Francisco and a Ph.D. in Animal Physiology at Mississippi State University, Dr. Chambers has developed an extraordinary career in education as well as research and service in the field of toxicology. She is now one of the few William L. Giles Distinguished Professors at Mississippi State University in recognition of excellence in all three areas of the academic triad, i.e., teaching, research and service, plus mentoring. Her contributions to educational programs are numerous. She taught physiology-related courses to a large number of students while on faculty in the Department of Biological Sciences, and after moving to the College of Veterinary Medicine, developed several toxicology courses. She maintains an active training program for graduate students and trained many Ph.D. students, most of whom are now active in the field of toxicology in academia or in government institutions. Recognizing her contributions to teaching, the Mississippi Board of Trustees of the Institutions of Higher Learning approved a Ph.D. program in Environmental Toxicology. More recently, she received a $10 million NCRR/NIEHS-funded Center of Biomedical Research Excellence (COBRE) award which was designed to nurture junior faculty members. While actively engaging in such multiple educational programs, she has made substantial progress in her research in pesticide toxicology. She was a recipient of numerous awards and honors, including the highly prestigious International Award for Research in Agrochemicals from the Agrochemical Division of the American Chemical Society, and the Burroughs Welcome Toxicology Scholar Award. She has been very active in various services such as participating on NIH Study Sections; SOT Continuing Education Committee, Education Committee, Membership Committee, and serving as SOT Secretary; U.S. EPA Scientific Advisory Panel for FIFRA and Human Studies Review Board; and ATSDR/NCEH Board of Scientific Counselors. Thus, Dr. Janice Chambers is not only outstanding in ducation but she is also making substantial contributions to toxicology research and service, and we honor her with the 2009 Education Award.

Serrine S. Lau

Serrine Lau, Ph.D., has made significant contributions in educating and developing new leaders in toxicology. Professor Lau received her Ph.D. in Pharmacology from the University of Michigan in 1980, followed by a postdoctoral fellowship in the laboratory of Dr. Jim Gillette at the NIH. Her first academic appointment was in 1986 at the University of Texas at Austin, where she became the first Endowed Assistant Professor in the history of the College of Pharmacy (COP), served as Director of a NIEHS supported training grant, Director of the Shortterm Research Training Program for Minority Students, and as Minority Liaison Officer for the COP in the University of Texas Graduate Outreach Program. Professor Lau is currently the Director of the Southwest Environmental Health Sciences Center at the University of Arizona, Scientific Director of the Arizona Proteomics Alliance, Associate Director of the NIEHS supported Toxicogenomics graduate training grant, and co-PI of the Summer Undergraduate Fellowship Program supported by ASPET. Professor Lau has published over 140 peerreviewed papers with the assistance of many talented students and postdoctoral fellows. Indeed, Professor Lau has mentored many high school, undergraduate, and graduate students who have gone on to successful careers in medicine, academia, government, and the private sector. Her students have won many awards, including two winners of the prestigious Carl C. Smith Graduate Student Award for Meritorious Research in Mechanisms of Toxicology. The success of Professor Lau’s students is a reflection of the unyielding passion that she brings each and every day to her laboratory, and her ability to encourage and cultivate scientific creativity. Professor Lau is a dynamic and powerful communicator, with the gift of being able to make complex subjects understandable and scientific research rewarding and enjoyable. Professor Lau has served on SOT Council, Awards Committee, Board of Publications, Education Committee, Task Force on Women in Toxicology, Task Force on Recruitment and Retention of Students in Toxicology, Task Force on NIH Funding, and as President of the Mechanisms Specialty Section. The Society of Toxicology recognizes Dr. Serrine S. Lau with the 2009 Education Award.

Sally Robinson

Sally Robinson, Ph.D., is honored by the Society of Toxicology for her contributions to the enhancement of animal welfare. The Enhancement of Animal Welfare Award is given in recognition of her vision, tenacity, expertise and determination to make a difference to the science of toxicology and animal welfare and her ongoing commitment to the 3Rs (Replace, Refine, or Reduce the need for experimental animals) at the international level.

Over the last five years, Dr. Robinson has led a crossindustry team, with support from the UK National 3Rs Centre (NC3Rs), that provided a novel, evidence-based challenge to the regulatory requirements for acute toxicity studies where lethality is an endpoint. Dr. Robinson initiated this project within her own company then collaborated with 17 other pharmaceutical companies globally to share data that were used to demonstrate that acute lethality toxicity studies have limited value to assess human safety. Therefore, requirements by regulators for these questionable experiments could not be justified.

The group’s results and recommendations have been presented to regulators from the European Union, United States, and Japan to raise awareness of the need to question the requirement for acute toxicity studies within international guidelines. These communications were successful and the ongoing revision of ICH M3 and the EMEA draft position paper on acute toxicity studies has incorporated the recommendations made by the group, citing the publications by Dr. Robinson, et al.

Dr. Robinson is Principle Toxicologist within Global Safety Assessment at AstraZeneca, Alderley Park in Cheshire, UK, specializing in animal ethics and the science of in vivo study design. She continues to promote enhancement of animal welfare, and to embed these modern concepts through mentorship of other toxicologists. We congratulate Dr. Robinson on these accomplishments and present the 2009 Enhancement of Animal Welfare Award.

Roger O. McClellan

Roger O. McClellan, D.V.M., is uniquely qualified for the Founders Award based on his outstanding leadership and accomplishments, all centered on understanding the effects of chemicals as a basis for minimizing human health risks. He supports the development of toxicological information from studies at multiple levels of biological organization, from macromolecules through populations of people or laboratory animals. This integration is most useful in predicting human health consequences of exposure to toxic agents. His experience of over 40 years in the fields of radiation, inhalation, and chemical toxicology have led to noteworthy publications and contributions clearly evident to SOT, as he has received the SOT awards for scientific achievements (Frank Blood, Arnold J. Lehman, and Merit).

His accomplishments also include outstanding leadership and strategic business analysis and planning for science-based organizations. He advocates the development of multi-discipline teams to address complex issues ranging from environmental health matters to new product development. He encourages critical analysis and revitalization of organizations through continuous improvement processes. His leadership is exemplified by his direction of the most distinguished toxicology research institutes in the world, the Lovelace Inhalation Toxicology Research Institute, now part of the Lovelace Respiratory Research Institute and the Chemical Industry Institute of Toxicology, now part of the Hamner Institutes for Health Sciences.

He currently is, or has been, an adjunct faculty member at 10 major research universities. He was elected to the Institute of Medicine of the National Academy of Sciences. He is a Diplomate of the American Board of Toxicology and the American Board of Veterinary Toxicology, and a Fellow of various societies, including the American Association for the Advancement of Science.

His outstanding leadership in fostering toxicology in safety decision-making through state-of-the-art approaches that elucidate the distinctions for humans between safe and unsafe levels of chemical exposures and the building of high-impact organizations leads us to enthusiastically bestow the Founders Award for 2009 on Dr. Roger O. McClellan.

John Katzenellenbogen

John Katzenellenbogen, Ph.D., recipient of the SOT Leading Edge in Basic Science Award, is an internationally recognized chemist who has been at the forefront of research on the structure and function of the estrogen receptor since the earliest days of his career at the University of Illinois when he developed one of the first high affinity labels for the receptor. Among his more recent contributions has been the development of novel ER agonist and antagonists with remarkable selectivity for ER α and β. He has freely provided these compounds to dozens of investigators worldwide, and their use has been instrumental in defining the roles of ERα and ERβ in mediating the diverse effects of endogenous, dietary, and environmental estrogens. Recently Dr. Katzenellenbogen has also expanded the structural universe of estrogen active compounds and has developed estrogen dendrimer conjugates as novel tools to study the non-genomic pathway of estrogen signaling. Together, these accomplishments have paved the way for endocrine toxicologists to identify specific targets and dissect complex pathways through which estrogenic endocrine disruptors act. During his distinguished career, Dr. Katzenellenbogen has published over 440 articles and trained over 80 doctoral and postdoctoral students, many of whom are now in leadership positions in academia or industry. The research career of Dr. John Katzenellenbogen provides a shining example of how the innovative investigations of a creative scientist can lead to a series of fundamental discoveries that drive many fields forward and that have profound impact on disciplines like toxicology. Dr. Katzenellenbogen is a superb example of a researcher making important contributions to the understanding of fundamental mechanisms of toxicity and thus is the first recipient of the Leading Edge in Basic Science Award.

Gilbert Omenn

Dr. Gilbert Omenn, M.D., Ph.D. has made tremendous contributions to public health, toxicology, and medicine and has been elected to 2009 Honorary Membership in the Society of Toxicology.

Dr. Omenn is Professor of Internal Medicine Human Genetics and Public Health at the University of Michigan. He is the director of the UM Center for Computational Medicine & Biology and the Proteomics Alliance for Cancer Research. He served as Executive Vice President for Medical Affairs and as Chief Executive Officer of the University of Michigan Health System from 1997 to 2002. He was formerly Dean of the School of Public Health, and Professor of Medicine and Environmental Health, University of Washington.

He served as Associate Director, Office of Science and Technology Policy, and Associate Director, Office of Management and Budget, in the Executive Office of the President in the Carter Administration. He is a longtime director of Amgen Inc. and of Rohm & Haas Company. He is a member of the Council and leader of the Plasma Proteome Project for the International Human Proteome Organization. He is Chairman of the Board (2006–2007) of the American Association for the Advancement of Science (AAAS). He is also on the advisory board of NextServices.

Dr. Omenn is the archetypal candidate for this honor based on his significant contributions to creating a safer and healthier world.

John E. Walker

Sir John E. Walker exemplifies a scientist who has made substantial contributions to the field of toxicology and has been elected to 2009 SOT Honorary Membership. Many SOT Annual Meeting attendees are familiar with Professor Walker form his attendance at the 2008 SOT Annual Meeting, presenting the MRC Lecture on Biological Energy Conversion and its Consequences. Professor Walker is employed by the MRC Dunn Human Nutrition Unit in Cambridge, UK. With co-recipient Paul D. Boyer, he received of the Nobel Prize for Chemistry in 1997 for their explanation of the enzymatic process that creates adenosine triphosphate (ATP).

Professor Walker was born in Halifax, Yorkshire in 1941. In 1960, he went to St. Catherine's College, Oxford, and received the B.A. degree in Chemistry in 1964. In 1965, he began research on peptide antibiotics with E. P. Abraham in the Sir William Dunn School of Pathology, Oxford, and was awarded the D.Phil. degree in 1969. This was followed a period of years working abroad, from 1969–1971 at the School of Pharmacy at the University of Wisconsin, and then from 1971–974 in France, supported by Fellowships from NATO and EMBO, first at the CNRS at Gif-sur-Yvette and then at the Institut Pasteur.

In 1974 Professor Walker joined the Protein and Nucleic Acid Chemistry (PNAC) Division at the LMB. In the early 1980s, he began studying ATP synthase, the central energyproducing molecule in most life-forms, which aides in the synthesis of ATP, the carrier of chemical energy. Focusing on the chemical and structural composition of the enzyme, he determined the sequence of amino acids that make up the synthase protein units. In the 1990s, working with X-ray crystallographers, he clarified the three-dimensional structure of the enzyme. His work supported Boyer’s “binding change mechanism,” which explained the unusual way in which the enzyme functions. Walker’s findings offer insight into the way life-forms produce energy.

Professor Walker received the A. T. Clay Gold Medal (1959). He was awarded the Johnson Foundation Prize by the University of Pennsylvania (1994), the CIBA Medal and Prize of the Biochemical Society (1996), The Peter Mitchell Medal of the European Bioenergetics Congress (1996), and the Gaetano Quagliariello Prize for Research in Mitochondria by the University of Bari, Italy (1997). In 1995, he was elected a Fellow of the Royal Society. In 1997, he was made a Fellow of Sidney Sussex College, Cambridge and became an Honorary Fellow of St. Catherine's College, Oxford.

Gary M. Williams

Gary Williams, M.D., is Professor of Pathology at New York Medical College. Dr. Williams has made a number of contributions to chemical carcinogenesis, particularly hepatocarcinogenesis. He conducted pioneering work in developing methods for the culture of hepatocytes and introduced the use of cultured hepatocytes to measure chemical-induced DNA repair synthesis as a means of identifying potential chemical carcinogens. Based in part on extensive findings with hepatocarcinogens in the hepatocyte system, he advanced the concept of distinct DNA-reactive and epigenetic mechanisms of carcinogenicity. He contributed to the understanding of liver neoplasia as a multi-step process involving the initiation of hepatocytes to form proliferative preneoplastic lesions identifiable by phenotype abnormalities, such as resistance to iron accumulation and expression of glutamine synthetase. Through assessment of the influence of hepatocarcinogens on the development of preneoplastic cells, he documented that DNA-reactive carcinogens rapidly induced such lesions, whereas epigenetic agents only slowly enhanced their expansion, thereby extending the understanding of different modes of action. Furthermore, he helped in distinguishing adaptive from adverse effects in the liver and other tissues. Also, Dr. Williams has investigated in depth the dose-response characteristics of DNA-reactive hepatocarcinogens. By quantifying key events, including DNA adducts, cytotoxicity, cell proliferation and induction of preneoplastic lesions, he has identified non-linearities and no effect levels at low doses for several DNA-reactive carcinogens. Dr. Williams has been involved in teaching toxicology through the organization of symposia and, for the past fifteen years, a course on safety assessment of medicines, and has advanced the discipline by serving on numerous advisory bodies and editorial boards. He received the Arnold J. Lehman Award in 1982 and the Enhancement of Animal Welfare Award in 2002 from SOT and the Ambassador in Toxicology Award from the Mid-Atlantic Regional Chapter of SOT in 2001. We congratulate and recognize Dr. Gary Williams as the recipient of the 2009 Merit Award.

Thomas W. Kensler

Thomas W. Kensler, Ph.D., is the 2009 Translational Impact Awardee. Dr. Kensler is currently Professor of Toxicology in the Department of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health where he holds a joint appointment in the Department of Biochemistry and Molecular Biology as well as in the Departments of Pharmacology and Molecular Sciences, and Oncology in the Johns Hopkins School of Medicine. Dr. Kensler has devoted much of his professional career to the development of molecular approaches to cancer prevention, seeking to develop the tools to test the hypothesis that enzyme induction through Keap1-Nrf2 signaling is a useful strategy for chemoprevention in humans. In the past decade, he has driven this science through several clinical trials towards practical strategies to affect a reduction of the impact of liver cancer in the economically developing world. He has provided outstanding leadership to bring together multidisciplinary teams of toxicologists, epidemiologists, biostatisticians and clinicians to the field of chemoprevention. Most importantly, he has managed to accomplish these achievements in a multicultural international setting.

Collectively Dr. Kensler has been a major contributor to the translational research efforts that are bringing new prevention opportunities to high-risk populations in the world. His work uses a foundation of rigorous, cuttingedge basic science to bring mechanism-based hypotheses into clinical trials. Over the past decade, this work has led to practical means for reducing the burden of environmentally-induced cancer in humans. These findings not only have importance in cancer research but have also been extended to the larger field of adaptive responses to many environmental stresses. Congratulations to Dr. Kensler, the first recipient of the Translational Impact Award.

Kim Boekelheide

Kim Boekelheide, M.D., Ph.D., is Professor of Pathology and Laboratory Medicine at the Brown University School of Medicine. His research focuses on fundamental molecular mechanisms by which environmental and occupational toxicants induce testicular injury, including the study of co-exposure synergy using model testicular toxicants and the effects of in utero endocrine disruptor exposure on steroidogenesis and a predisposition to cancer. The AstraZeneca Traveling Lectureship Award recognizes excellence in research and service in toxicology and enables a lecture tour of Europe to promote collaboration between European and North American toxicologists. He will use this award to address two hot topics—a discussion of the future of toxicity testing and the development in his laboratory of a novel xenotransplant model to investigate the human testicular response to in utero active endocrine disruptors. At both industrial and academic institutions in Europe, Dr. Boekelheide’s lecture series is designed to stimulate thoughtful discussion of both science policy and basic research in the toxicological sciences with cross-cutting and timely new perspectives with relevance to regulatory issues. We recognize Dr. Kim Boekelheide with the 2009 AstraZeneca Traveling Lectureship Award.

The Board of Publications has selected the paper entitled "The PPARα- Humanized Mouse: A Model to Investigate Species Differences in Liver Toxicity Mediated by PPARα" as the best paper published in Toxicological Sciences in the past year (ToxSci 2008, 101:132–139). The authors of the paper are Qian Yang, Tomokazu Nagano, Yatrik Shah, Connie Cheung, Shinji Ito, and Frank J. Gonzalez.

The paper describes the development and phenotypic characterization of a PPARα-humanized transgenic mouse that was generated on a mouse pparα-null background using the complete human PPARα gene (designated hPPARαPAC). Importantly, this model expressed hPPARα in both hepatic and extra-hepatic tissues, including heart, kidney and intestine. The development of this model represents an important new tool for evaluating the physiologic and toxicologic consequences of PPARα activation. For example, although fenofibrate elicited similar responses in peroxisome proliferation and lipid lowering in wildtype and hPPARαPAC mice, reduced serum lipids in hPPARα^PAC mice were not accompanied by the expected increased expression of lipoprotein lipase and decreased expressed of apolipoprotein C-III. These results challenge present assumptions regarding the mechanisms by which peroxisome proliferators (PPs) exert their hypolipidemic effects and demonstrate the need to reevaluate this purported mechanism. In addition, the research provided novel insights into species differences in hepatic cell proliferation in response to PPs, as hPPARα^PAC mice showed no evidence of hepatomegaly, cell proliferation or PP-induced expression of CDK4 and cyclin D1, and no change in expression of hepatic miRNA let-7C and c-Myc expression. These results identify an important species difference in response to PPs, in that unlike mice, human PPARα activation is not associated with hepatocyte proliferation. However, no difference in ligand affinity between mouse and human PPARα was observed, thereby challenging another property proposed to explain species differences in response to PPs. In total, the development of hPPARα^PAC mice provides important new and novel insights into the function of PPARα in humans and is the foundation for identifying the molecular mechanisms underlying species differences in response to PPs that will ultimately help to refine the human risk assessment for this important class of compounds.