Society of Toxicology (MASOT) http://www.masot.org Fall 2014 Scientific Meeting Sheraton Hotel, Raritan Center, Edison, NJ The Mid-Atlantic Chapter of the Society of Toxicology (MASOT) was formed to: (1) serve as a focal point for toxicological interests within the region; (2) encourage interactions among toxicologists in government, industry, and academia; and, (3) sponsor scientific and educational programs in toxicology. The Chapter and its bylaws were officially approved by the Council of the Society of Toxicology at the March 1982 Annual Meeting. The bylaws were last revised and approved in September 2012. MASOT Fall Meeting 2014 Program Committee (2014-2015) Richard Hutchinson John Kozlosky John Mitchell Robert Parker Gloria Post Mindy Reynolds Ric Stanulis Puneet Vij Arlene Weiss Lauren Aleksunes Eric Beier Conney Berger, Jr. Kristin Bircsak Angelique Braen Todd Davidson George DeGeorge (Chair) Shayne Gad Jedd Hillegass Officers (2014-2015) President: Vice-President: Vice-President Elect: Secretary: Treasurer: Councilors: Past President: Post-Doctoral Representative: Senior Student Representative: Junior Student Representative: Conney Berger, Jr. George DeGeorge Richard Hutchinson Valerie Shultz Jennifer Ingram-Ross Lauren Aleksunes Todd Davidson Jedd Hillegass Ric Stanulis Eric Beier Puneet Vij Kristin Bircsak Visit MASOT at http://www.masot.org, on Linked In, and on Twitter at @MidAtlSOT 2 MASOT Fall Meeting 2014 MASOT FALL MEETING October 16, 2014 Exploring the Human Microbiome: Roles in Disease, Toxicology, and Drug Development 9:00 – 9:30 Registration/Networking Continental Breakfast 9:30 – 9:45 Welcome and MASOT Update – Dr. Conney Berger Program Introduction – Dr. George DeGeorge 9:45 – 10:30 Dr. Jeffrey Boscamp (Hackensack University Medical Center) Title: The Human Microbiome: Will It Define Health and Disease? 10:30 – 11:15 Student Poster Session 11:15 – 12:00 Dr. Rodney Dietert (Cornell University) Title: The Human Microbiome: Developing and Maintaining a Healthy Superorganism 12:00 – 2:00 Ambassador Award/Lunch Dr. Michael Holsapple (Covance) Title: Some Personal Reflections on the Evolution of Toxicity Testing over a 30+ Year Career 2:00 – 2:30 Dr. Michal Toborek (University of Miami) Title: Who is Running Your Gut: Impact of PCBs and Exercise on the Gut Brain Axis 2:30 – 3:00 Student Poster Session 3:00 – 3:30 Dr. Kimberly Capone (Johnson & Johnson) Title: Exploration of the Changes in the Human Skin Microbiome as We Age and the Effects of Common Hygiene Practices on Bacterial Diversity 3:30 – 4:00 Dr. James R. Brown (GlaxoSmithKline) Title: Human-Microbial Interactions in Drug Discovery 4:00 – 4:30 Dr. Geoffrey K. Hogan, Ph.D., DABT Memorial Scholarship/Travel Award Student Poster Awards Closing Comments – Dr. George DeGeorge 3 MASOT Fall Meeting 2014 The Human Microbiome: Will It Define Health and Disease? Jeffrey Boscamp, M.D. (Hackensack University Medical Center) Dr. Boscamp is Vice President and Chief Academic Officer at Hackensack University Medical Center as well as the Marvin I. Gottlieb, M.D., Ph.D. Chairman of Pediatrics and Physician-In-Chief of the Joseph M. Sanzari Children’s Hospital. He is an Associate Professor of Pediatrics at the Rutgers-New Jersey Medical School. Dr. Boscamp is the founder of the Section of Pediatric Infectious Diseases and of the Steven Bader Immunologic Institute at Hackensack University Medical Center. Dr. Boscamp received his B.A. from Williams College (Williamstown, MA) and his M.D. from New York Medical College (New York, NY). He was a Research Associate at Harvard Medical School (Boston, MA) and did his pediatric residency at Babies Hospital, Columbia Presbyterian Medical Center (New York, NY). After completing pediatric training, he was a resident in internal medicine at Yale University School of Medicine, Greenwich Hospital (Connecticut). He subsequently completed a fellowship in adult and pediatric infectious diseases at the Albert Einstein College of Medicine (Bronx, NY). Dr. Boscamp joined the medical staff at Hackensack University Medical Center in 1987, and was appointed Chief of the Section of Pediatric Infectious Diseases in 1990. At Hackensack University Medical Center he is a Consultant to the Institute for Child Development and the Tomorrows Children’s Institute for Cancer and Blood Disorders. He is a Consultant in Pediatric Infectious Diseases at Morristown Memorial Hospital (Morristown, NJ) and Holy Name Hospital (Teaneck, NJ). Dr. Boscamp is Chairman of the NJ Chapter, American Academy of Pediatrics, Committee on Infectious Diseases and a member of the executive committee of that organization. Dr. Boscamp is also a member of the NJ Pediatric Leadership Council, and was appointed by the Governor as a member of the Catastrophic Illness in Children Relief Fund Commission. He is a fellow of the AAP and the Pediatric Infectious Diseases Society. He is also a member of the Infectious Diseases Society of America, the Infectious Diseases Society of New Jersey, and the American Society for Microbiology. Dr. Boscamp is board-certified in Pediatric Infectious Diseases, is a member of Alpha Omega Alpha, and was the recipient of the Lawrence B. Slobody Prize in Pediatrics at New York Medical College. In 1993, he received the Outstanding Teacher Award in Pediatrics at Morristown Memorial Hospital, and in 1998 was recognized with the Attending of the Year Award in the Department of Pediatrics at the UMDNJ-New Jersey Medical School. Abstract: The population of microorganisms that live within the human body is known as the human microbiome, and ongoing research has shown that the interaction between human cells and the bacterial cells we live with plays a large role in health and disease. The human microbiome may be involved in disease states such as allergy, asthma, inflammatory bowel disease, high blood pressure, heart disease, obesity and cancer. Rapid advances are occurring in this field and this lecture will outline the presence of microbial communities within the human body, how they communicate and how they might be “managed” to promote health. Research in this area is already translating to clinical advances and this lecture will review recent studies that are already changing clinical practice. The Human Microbiome: Developing and Maintaining a Healthy Superorganism Rodney Dietert, Ph.D. (Cornell University) Dr. Rodney Dietert is Professor of Immunotoxicology in the Department of Microbiology and Immunology at Cornell University. He received the BS degree from Duke University and his PhD from University of Texas at Austin and is beginning his 38th year on the Cornell faculty. Rodney has served as President of the Immunotoxicology Specialty Section of the SOT, Director of Cornell’s Institute for Comparative and Environmental Toxicology, Director of Graduate Studies for the Cornell Graduate Field of Immunology, Senior Fellow in the Cornell Center for the Environment, and Director of the Program on Breast Cancer and 4 MASOT Fall Meeting 2014 Environmental Risk Factors. He is currently the editor of Springer’s book series Molecular and Integrative Toxicology. Rodney has more than 300 publications covering aspects of early life development and health risks. Rodney’s most recent endeavors include his appearance in the 2014 documentary film on the microbiome titled, Microbirth, and development of a science-oriented creative problem-solving curriculum previously offered at an SOT annual meeting and presented most recently at Cornell’s 2014 Orientation Program for new students. Abstract: The recent realization, that humans in their normal, healthiest state are a majority-microbial superorganism, has shifted the fundamental nature of the target organism that has driven human toxicology, drug development, public health and specialized medicine. Purely mammalian-centric data seems likely to be viewed as insufficient to drive this science and policy, and contextual data for the superorgansim is likely to take on an increasing importance. Such a shift should open up new opportunities in toxicology, pharmacology, drug discovery and medicine. The presentation introduces potential priority parameters for early-life management, chemical and drug safety, and pharmacologic-based therapies oriented toward the “Completed Self” model of a healthy life course. Among the topics considered is the role of the microbiome in: 1) developmental maturation of the immune system, 2) host exposure and toxicity, 3) effective nutrition and lifestyle options, and 4) potential drug-based therapies. Ambassador Award Lecture – Some Personal Reflections on the Evolution of Toxicity Testing over a 30+ Year Career Michael P. Holsapple, Ph.D., A.T.S. (Covance) Dr. Holsapple is a toxicologist with over 30 years of experience. He received his graduate training in Pharmacology and Toxicology from Purdue University, having earned an M.S. in 1978 and a Ph.D. in 1981. From 1983–1994, he served on the faculty at the Medical College of Virginia/Virginia Commonwealth University in Richmond, VA. During his academic career, he maintained consistent funding with grants from NIH, NIDA and EPA, and he served as the advisor for 8 Ph.D. and M.S. candidates, and as a member of the doctoral dissertation committees for 21 other students. From 1994-2002, Dr. Holsapple worked in the Toxicology, Environmental Research and Consulting Laboratories at the Dow Chemical Company in Midland, MI. During his industry career, as a Senior Research Leader, his responsibilities included leading both the Immunotoxicology and the Respiratory Toxicology groups. From 2002-2011, Dr. Holsapple served as the Executive Director of the Health and Environmental Sciences Institute (HESI), the global branch of the International Life Sciences Institute (ILSI) in Washington, DC. During his time with HESI, Dr. Holsapple facilitated the organization’s emergence as a recognized global leader in advancing the state-of-the-science of safety and risk assessment. Dr. Holsapple joined the Battelle Memorial Institute in Columbus, OH, as a Senior Research Leader in systems toxicology on August 1, 2011. On January 27, 2014, he joined Covance Laboratories in Madison, WI, as the Executive Director of Global Immunotoxicology. Dr. Holsapple has published over one hundred and fifty manuscripts and chapters. In recognition of his contributions to toxicology, Dr. Holsapple received the Society of Toxicology (SOT) Achievement Award in 1992. In recognition for his contributions to immunotoxicology, he received the Vos Award – Career Achievement in Immunotoxicology in 2009. Dr. Holsapple served on Council for the SOT from 2005-2007, and on Council for the American College of Toxicology (ACT) from 2003-2006. He was elected into the Presidential track of the SOT in 2008, and presided over the organization’s 50th Annual Meeting in 2011. Dr. Holsapple was elected a ‘fellow’ in the Academy of Toxicological Sciences (ATS) in 2006, a member of the Board of Trustees of the ATS in 2013, and is currently serving as the Vice President of the ATS Board. 5 MASOT Fall Meeting 2014 Who is Running Your Gut: Impact of PCBs and Exercise on the Gut Brain Axis Michal Toborek, M.D., Ph.D. (University of Miami School of Medicine) Dr. Michal Toborek is Leonard M. Miller Professor of Biochemistry and Molecular Biology and Vice-Chair for Research in the Department of Biochemistry and Molecular Biology at the University of Miami School of Medicine. He received his MD (1985) and PhD (1989) degrees from the Silesian Medical University, Poland, and completed his postdoctoral training at the University of Kentucky. Dr. Toborek joined the faculty at the University of Kentucky in 1996, initially as Research Assistant Professor, and rose to the ranks becoming a full Professor in 2005. He transferred to the University of Miami in 2011. Research in Dr. Toborek’s laboratory has been focused on several aspects of vascular biology. Specific interest involves studies on the integrity of the blood-brain barrier (BBB) and how different pathological conditions can lead to the disruption and/or dysfunction of the BBB. Several projects in his laboratory are related to the interactions between environmental factors, such as polychlorinated biphenyls (PCBs) or nanoparticles with diets or exercise on BBB integrity. Another area of his research is on the effects of HIV on metabolism and function of the BBB. His research is supported by several NIH and AHA grants and he currently has 10 researchers in his laboratory. Dr. Toborek has a strong record of training and advising postdoctoral scholars and graduate students. To his merit, 12 of his past postdoctoral scholars have received faculty positions in the US or aboard. Dr. Toborek has published extensively on endothelial cell metabolism and the integrity of the biological barriers, such as the BBB and the intestinal barriers. Dr. Toborek has received several national and international awards for his research in vascular biology, such as the Excellence in Research Award from the American Heart Association, the Anafred N. Halpern Award from the American College of Nutrition, and twice the International Alexander von Humboldt Research Award. He is a founding member of the International Brain Barriers Society, a member of the Scientific Council for the International Symposia on Signaling at the BBB, and the Associate Editor of a journal “Tissue Barriers”, where he is responsible for the blood-brain barrier section. Dr. Toborek was elected a councilorat-large of the Society of Immune Pharmacology (SNIP) in 2011. He is the current Secretary for the SNIP and a member of the SNIP Executive Committee. He received the 2014 Wybran Award, which is “the highest honor bestowed by SNIP in recognition of the very best scientific contributions that have resulted in the preservation and expansion of the field of NeuroImmune Pharmacology.” He recently (2014) co-edited with Dr. Philip Peterson a book “Neuroinflammation and Neurodegeneration” (Springer). Abstract: The gut microbiome is a dynamic bacterial community that interacts with the host and closely relates to human health by regulating energy metabolism and immune functions. The influence of the microbiome on the toxicity of environmental pollutants and its role in risk assessment are largely unknown. In addition, there is an emerging interest in the role of behavioral factors in modulating toxicity of environmental pollutants. Because exercise can influence the outcomes of disorders known to be associated with alterations of the gut microbiome, we hypothesized that physical activity may affect the composition of the gut microbiota and thus influence the impact of environmental toxicants. Mice exercised voluntarily for 5 weeks, followed by the exposure to a mixture of environmentally relevant PCB congeners (PCB153, PCB138 and PCB180). The microbiome was assessed by determination of 16S rRNA. Oral exposure to PCBs disrupted the integrity of the gut barrier function and significantly altered the abundance of the gut microbiome primarily by decreasing the levels of Proteobacteria. The activity level correlated with a substantial shift in abundance, biodiversity, and microbiome composition. Importantly, exercise attenuated PCB-induced changes in the gut microbiome. Oral exposure to PCBs facilitated the development of brain metastases, the effects that was attenuated by exercise. This study provides the first evidence that oral exposure to PCBs can induce substantial changes in the gut microbiome, which may then influence their systemic toxicity. Importantly, these changes can be attenuated by behavioral factors, such as voluntary exercise. 6 MASOT Fall Meeting 2014 Exploration of the Changes in the Human Skin Microbiome as We Age and the Effects of Common Hygiene Practices on Bacterial Diversity Kimberly Capone, Ph.D. (Johnson & Johnson) innovation. Kimberly Capone received her Ph.D. in Microbiology and Immunology from Northwestern University in Chicago, IL in 2006. While her graduate research focused on understanding the role of iron acquisition in the pathogenesis of Legionella pneumophila, her most recent work is aimed at understanding the role of the skin microbiome in human health, particularly early in life. She is currently a Research Fellow with Johnson & Johnson Consumer & Personal Products Worldwide, in Skillman, NJ where she leads a team responsible for skincare product Abstract: The skin microbiome colonizes humans at birth but the community structure and diversity continue to change throughout the course of life. These community changes correlate with the various microenvironments on the skin as well as changes in skin structural and functional properties over time. To examine the alterations of the skin microbiome throughout life, we explored the longitudinal development of the skin microbiome in infants from 3 weeks of age to 5 years old, as well the community structure of the skin microbiomes of children age 6-12, and adults from 25-69. The dominant members of the skin microbiome community change over time from infancy to older adulthood. Importantly, among other changes, the skin microbiome of infants and older adults contained less Propionibacteria than found in younger adults. In addition to the changes in the skin microbiome that naturally occur over the course of our lives, the hygiene and personal care products we use may play a role in altering the skin microbiome. To examine the effects of hygiene practices on the skin microbiome, we explored the effects of a castile soap and a mild cleanser over 4 weeks of use. The skin microbiomes of both cohorts were significantly different and the community structures were distinct at the end of the study. The major differences in the skin microbiome throughout life as well as the fact that different hygiene practices alter it in distinct ways, support the need for further exploration into the role of various skin microbiome communities in overall skin health and the development of dermatological diseases. Human-Microbial Interactions in Drug Discovery James R. Brown, Ph.D. (GlaxoSmithKline) Dr. James (Jim) Brown is presently Director, Computational Biology Therapeutic Area Contact for Infectious Diseases in GlaxoSmithKline (GSK) and is based in Collegeville, Pennsylvania. He has nearly 18 years experience in providing bioinformatics support to the discovery and development of small molecules, biologicals, vaccines and diagnostics primarily in the therapeutic areas of infectious disease and cancer. He also heads the Microbiome Matrix Team which coordinates microbiome research throughout GSK R&D. Previously, Jim was a Medical Research Council of Canada post-doctoral fellow at Dalhousie University, Halifax. His M.Sc. and Ph.D. degrees are from Simon Fraser University, Vancouver in marine ecology and molecular population genetics, respectively; with a B.Sc. Marine Biology from McGill University. He has authored over 90 publications and given many conference presentations. His research interests include molecular evolution, host-pathogen interactions, infectious disease and the microbiome. Abstract: Traditionally, infectious pathogens and chronic diseases, such as obesity and diabetes, have been separate research disciplines. However, recent advances in genomics and bioinformatics are rapidly opening a deeper dialogue between these fields. The human body supports dynamic and complex ecosystems of microorganism known as the microbiome. The human gut alone has more than 1000 different bacterial species with a cell count ten-fold greater than all cells in a human being. Understanding the diversity of the microbiome in human populations and its role in human health could provide new therapeutic paradigms for many chronic diseases. Conversely, high throughput genomics platforms are providing new insights into the interplay between human and pathogen genes during infection – the so-called host-pathogen interactome. This presentation will discuss the opportunities and challenges in translating both the microbiome and interactome from basic science into clinical therapies using specific examples from our drug discovery programs. 7 MASOT Fall Meeting 2014 Dr. Geoffrey K. Hogan, Ph.D., DABT Memorial Scholarship/Travel Award The Dr. Geoffrey K. Hogan, Ph.D., DABT Memorial Scholarship/Travel Award is a $1000 award that will be given to a Ph.D. student annually in memory of Dr. Geoffrey Hogan (June 09, 1940 - February 23, 2011). The award was initiated in 2011 through the generosity of Huntingdon Life Sciences. Mrs. Barbara Hogan has graciously agreed to continue this tribute. Dr. Hogan earned his M.A. in Public Health and later a Ph.D. in Toxicology from the University of Michigan. Among his many accomplishments, Dr. Hogan was the President of Bio/dynamics (currently Huntingdon Life Sciences), and later was Director of Applied Bioscience International. Dr. Hogan had a great interest in the application of toxicology to the protection of human health. This award is a tribute to his efforts towards this goal. 8 MASOT Fall Meeting 2014 MASOT Meeting Sponsors Gold ($1000 - $2000) 9 MASOT Fall Meeting 2014 MASOT Meeting Sponsors Silver ($500 - $1000) Gad Consulting Services 10