Scientific Program Overview (dates and times)
2012 SOT Landmarks Program Presentation
The Ames Test
Exhibit Hall E
Monday, March 12, 7:45 AM–8:00 AM
Lecturer: Bruce Ames, Institute for Systems Biology (ISB) in Seattle, WA
Developed by Dr. Bruce Ames and his colleagues in the early 1970s, the Ames Test invigorated the field of genetic toxicology and continues to have broad application in safety assessments by government and industry. The test is a biological assay to assess the mutagenic potential of chemical compounds. A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, since cancer is often linked to mutation. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound since standard carcinogen assays on rodents is time-consuming (taking around three years to complete) as well as expensive. The Ames Test is often used as one of the initial screens for potential drugs to weed out possible carcinogens, and it is one of the eight tests required under the Pesticide Act (USA) and one of six tests required under the Toxic Substances Control Act (USA). The test revolutionized the field of genetic toxicology and stimulated new directions in cancer research. It has broad application in pharmaceutical, pesticide, industrial chemical and environmental sample testing and it has also reduced animal use in testing.
Plenary Opening Lecture
Systems Medicine, Systems Toxicology, Transformational Technologies and the Revolution from Reactive to Proactive (P4) Medicine
Exhibit Hall E
Monday, March 12, 8:00 AM–9:00 AM
Lecturer: Leroy Hood, Institute for Systems Biology (ISB) in Seattle, WA
The challenge for biology in the twenty-first century is the need to deal with its incredible complexity. One powerful way to think of biology is to view it as an informational science. This view leads to the conclusion that biological information is captured, mined, integrated by biological networks, and finally passed off to molecular machines for execution. Hence the challenge in understanding biological complexity is that of deciphering the operation of dynamic biological networks across the three time scales of life—evolution, development, and physiological responses. Systems approaches to biology are focused on delineating and deciphering dynamic biological networks and their interactions with simple and complex molecular machines.
Dr. Hood’s focus will be on our strategies for taking a systems approach to disease—looking at prion disease and liver toxicity in mice. We have published a study on prion disease that has taken more than 6 years—that lays out the principles of a systems approach to disease including new insights into pathophysiology, new approaches to diagnosis and therapy as well as dealing with the striking signal to noise problems of high throughput biological measurements and biology itself. We have also studied two types of liver toxicity and these studies have also yielded insights similar to those discussed above. We have made blood a window for assessing health and disease through the use of blood organ-specific markers (for both brain and liver).
Dr. Hood will also discuss the emerging technologies (measurement and visualization) that will transform medicine and the analyses of toxicity over the next 10 years—including next generation DNA sequencing, targeted mass spectrometry, micro-fluidic protein chips, and single-cell analyses.
It appears that systems approaches to disease, together with pioneering changes in technology and the development of powerful new computational and mathematical tools will transform medicine over the next 5–20 years from its currently reactive state to a mode that is predictive, personalized, preventive, and participatory (P4).
In conclusion, Dr. Hood will describe what P4 medicine will do for the individual patient. He will also consider the societal impact of P4 medicine and how ISB has created global strategic partnerships to bring P4 medicine to patients.
Keynote Medical Research Council (MRC) Lecture
Role of microRNAs in Control of Gene Expression in Human Physiology and Pathology
Tuesday, March 13, 8:00 AM–9:00 AM
Lecturer: Witold Filipowicz, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
MicroRNAs (miRNAs) are a novel class ~20-nt-long regulatory RNAs expressed in eukaryotes. MiRNAs regulate gene expression post-transcriptionally, by imperfectly base-pairing to 3’UTR of mRNAs, what results in translational repression or mRNA deadenylation and degradation. The number of different miRNAs in humans reaches ~1,000, and ~50% of all human genes are predicted to be subject to miRNA regulation. Although specific functions and target mRNAs have been assigned to only a fraction of identified miRNAs, much evidence exists that miRNAs participate in the regulation of nearly all cellular and developmental processes. Expression of many miRNAs is tissue or development specific and major changes in miRNA expression are observed in human pathologies, including cancer. Clearly, discovery of miRNAs added a new dimension to the complexity and regulation of eukaryotic genomes.
This lecture will provide current knowledge about the mechanism of miRNA-mediated repression of gene expression, procedures to identify miRNA targets, as well as a role of miRNAs in selected human pathologies and the use of miRNA profiling as a diagnostic tool in human diseases and in tissue and cell injuries. MiRNAs has been found to be secreted from cells via exosomes and their profiling in human serum and other body fluids appears to be a promising diagnostic tool in different pathologies. MiRNAs may also play important roles in cellular responses to xenobiotic stresses and in control of drug-metabolizing enzymes. In addition, miRNAs or compounds blocking their function represent promising therapeutic agents.
Meet the Directors
Wednesday, March 14, 9:00 AM–11:45 AM
Chairperson(s): William Slikker Jr., US FDA, Jefferson, AR, and Lois D. Lehman-McKeeman, Bristol-Myers Squibb Company, Princeton, NJ
Each year this unique session provides an opportunity for the leaders of agencies to provide an overview of their organizations, scientific directions, funding opportunities, and scientific concepts/achievements. This year, our panel of experts—Chris Portier, Agency for Toxic Substances and Disease Registry (ATSDR), Linda S. Birnbaum, National Institute of Environmental Health Science (NIEHS), Paul Anastas, US Environmental Protection Agency (US EPA), and Jukka Malm, European Chemical Agency (ECHA) will provide information of interest to the SOT membership during their individual talks.
We hope you’ll join them as they deliver the most recent updates related to important issues that have an impact on toxicology.
Merit Award Lecture
Reprogramming the Liver
Monday, March 12, 12:30 PM–1:20 PM
Lecturer: Curtis D. Klaassen, University of Kansas Medical Center, Kansas City, KS
Leading Edge in Basic Science Award Lecture
Inorganic Phosphate: Hidden Signal?
Tuesday, March 13, 7:00 AM–7:50 AM
Lecturer: Myung-Haing Cho, Seoul National University, Seoul, South Korea
Inorganic phosphate (Pi) is being added to a large number of processed foods because the addition of Pi increases the quality of food through improved water retention and texture. Surveys conducted in various countries indicate that intake of Pi has increased steadily as Pi-containing foods increased. These surveys also suggest that the use of Pi as a food additive may continue to increase. Pi plays a key role in diverse physiological functions. Several studies indicate that Pi may affect lung cell development through Na/Pi co-transporter (NPT). Some NPT subtypes have been identified in mammalian lung and considerable progress has been made in our understanding of their function and regu-lation. Therefore, we have been tried to elucidate the potential effects of high dietary Pi. Our results clearly demonstrate that high dietary Pi may affect the lung development. Also, we show that high dietary Pi promotes lung tumorigenesis through Akt-related cap-dependent protein transla-tion, cell cycle regulation, and angiogenesis. Our results support the hypothesis that Pi works as a stimulus capable of increasing or decreasing several pivotal genes for lung cancer growth and suggest that regulation of Pi consumption may be important in maintaining a high quality of life.
Distinguished Toxicology Scholar Award Lecture
Environmental Chemicals: from Biochemical and Molecular Toxicology to Education and Outreach
Tuesday, March 13, 12:30 PM–1:20 PM
Lecturer: Ernest Hodgson, North Carolina State University, and the North Carolina Agromedicine Institute, Raleigh, NC
Knowledge of modes of toxic action and risk analysis are approaching the point where systems biology will be essential for understanding. Human environments are also complex, from pristine ecosystems to those contaminated by human activities such as the agroecosystem, industrial workplaces, military deployments, and home environments. Each environment has numerous variants that overlap within and between categories and the exposome concept may also become essential. The speaker has been fortunate to be involved in a number of these aspects and as Distinguished Toxicology Scholar has an opportunity to discuss their past, present, and future. Successes, failures, and disappointments include such items as the mechanism of action of benzodioxole synergists, aryl hydrocarbon receptor(AhR)-independent induction of cyp1a2, human metabolism of agrochemicals, metabolic interactions, and agromedicine. Our studies have identified environmental chemicals that interact in humans based on induction, on enzyme inhibition by organophosphorus toxicants of both exogenous substrate and steroid hormone metabolism and on activation of naphthalene metabolism. Microarray studies of the effect of chlorpyrifos on gene expression in human hepatocytes identified regulated genes and characterized the affected biological pathways.
Translational Impact Award Lecture
Medical Toxicology Evaluations of the 2008 TVA Fly Ash Spill
Wednesday, March 14, 12:30 PM–1:20 PM
Lecturer: John G. Benitez, Vanderbilt University Medical Center, Nashville, TN
At approximately 1:00 am on December 22, 2008, the retaining dike broke at the TVA Kingston Fossil Plant, releasing more than 5.4 million cubic yards of coal ash onto TVA property, private property and the Emory River. The ash flow filled several sloughs with ash debris and embankment material. The communities surrounding the spill site had an additional concern regarding health risks because of living next to the site, ash on their property, the emergency response, and planned remediation efforts. Through partnership with the Oak Ridge Associated Universities and the Tennessee Poison Center, residents living in the vicinity of the Kingston TVA plant had medical evaluations by a medical toxicologist including a history and physical exam, routine laboratory evaluations, pulmonary function testing, chest radiographs, and blood and urine metal evaluations. Three hundred twenty participants signed up initially; 200 were seen by the medical toxicologist. One hundred ninety-eight of these had blood and urine testing, 208 had chest radiographs, and 194 had pulmonary function tests. Many participants had ear, nose, throat, and pulmonary complaints. No pattern of heavy metal exposure, abnormal blood testing, pulmonary function testing, and chest radiographs were found.
Comparative Hazards: Chemicals in the Environment Are the Largest Risk to Human Health
Monday, March 12, 4:30 PM–5:50 PM
Chairperson(s): Lois D. Lehman-McKeeman, Bristol-Myers Squibb Company, Princeton, NJ, and Nancy Claude, Institut de Recherches Internationales Servier, Courbevoire, France
SOT Debater: Stephen Safe, Texas A&M University, College Station, TX
EUROTOX Debater: David R. Bell, European Chemicals Agency, Helsinki, Finland
Endorsed by: Society of Toxicology (SOT)
European Societies of Toxicology (EUROTOX)
Each year the SOT Annual Meeting includes a debate that continues a tradition that originated in the early 1990s in which leading toxicologists advocate opposing sides of an issue of great toxicological importance. This year, our debaters will address the proposition: Comparative Hazards: Chemicals in the Environment Are the Largest Risk to Human Health.
Chemicals have been introduced into the environment through a variety of industrial and agricultural processes. They are measured in the air we breathe, the water we drink and the food we eat. Although there are many chemicals that serve to improve the quality of life, there are also unintended hazards that are associated with their use. This debate is intended to focus on chemicals in the environment as the largest risk to human health, particularly when compared to other potential health hazards.
Regardless of framework differences and personal convictions, each scientific delegate will present relevant evidence and compelling scientific arguments to persuade and appeal to the response of the audience in order to obtain the approval or refusal of the motion. In addition to being a featured session at the SOT Annual Meeting, this debate will again take place in Stockholm, Sweden during the 2012 Eurotox Annual Congress, June 17–20.
Research Funding Sessions
Research Funding Information Room
Tuesday, March 13 and Wednesday, March 14, 9:00 AM–4:30 PM
Chairperson (s): Nancy Kerkvliet, Oregon State University, Corvallis, OR
Sponsor: Research Funding Committee
Program and review staff from agencies that fund research, including NIH and the Center for Scientific Review, NIEHS will be available in the Research Funding Information Room for individual conversations. Check the posted schedule at the NIEHS booth (2037) for specific times staff members will be available to answer your questions about scientific review or grant opportunities. The schedule also will be available at the registration area and in Room 206, site of the “Strategies for Submitting Successful Grants: Brown Bag Lunch.”
Brown Bag Luncheon
Tuesday, March 13, 12:00 Noon–1:30 PM
Chairperson(s): Nancy Kerkvliet, Oregon State University, Corvallis, OR
Sponsor: Research Funding Committee
This investigators’ luncheon focuses on strategies for submitting successful grant packages. Panelists will be on hand to talk about the ins and outs of what makes a successful grant submission, what you should do before putting pen to paper, how to write the grant, what strategies are used to help make grant submissions stand out, and how the application progresses through the review process. Panelists for this brown bag luncheon include Dr. Janice Benson-Allen, Scientific Review Officer, National Institute of Environmental Health Sciences, Dr. Heather B. Patisaul, Assistant Professor, North Carolina State Univer-sity, and Dr. Stacey Lynn Harper, Assistant Professor, Oregon State University.
Building for the Future: Strategic Initiatives for the SOT Endowment Fund
Thursday, March 15, 7:30 AM–8:50 AM
Chairperson(s): Norbert E. Kaminsky, Michigan State University, East Lansing, MI, and Lois D. Lehman-McKeeman, Bristol-Myers Squibb Company, Princeton, NJ
An important goal emerging from the Society’s strategic initiatives is to continue support of programs and activities that cultivate the long-term interests and professional development of its members. Achieving this goal requires sufficient resources to address specific needs, including adequate research funding and providing the next generation of scientists with the tools and opportunities to advance their science and facilitate harmonization in a global marketplace.
As part of the strategic plan, SOT Council has directed the SOT Endowment Fund Board to develop aspirational goals that would generate the enthusiasm necessary to grow the Endowment Fund and to initiate new activities that broadly support membership development and engagement.
We invite you to join us for this very informative and important Issues Session. We will discuss the strategic initiatives and plans to create a margin of excellence for supporting the priority needs and advancing the science of toxicology. We also encourage and value membership input and perspective on these efforts, particularly in this critical early stage when plans are being developed.
Regional Interest Sessions
Bridging the Green Chemistry Gap between Product Discovery and Availability
Monday, March 12, 2:00 PM–4:45 PM
Chairperson(s): Abby A. Li, Exponent Health Sciences, San Francisco, CA, and Lauren Zeise, Cal/US EPA, Berkeley, CA.
Sponsor: Ethical, Legal, and Social Issues Specialty Section
Endorsed by: Occupational and Public Health Specialty Section
Regulatory and Safety Evaluation Specialty Section
Risk Assessment Specialty Section
Recent government and industry initiatives seek to identify chemicals of toxicological concern in products to reduce their use or replace them with safer chemicals. At the same time, sustainable approaches to product manu-facture and use that account for energy consumption, product life cycle, and societal benefit are being emphasized. This creates the challenge of developing sound scientific approaches for identifying important chemical hazards and evaluating alternative, safer chemicals or products, all done within the context of risk and benefit trade-offs. Two laws recently passed in California (Chapters 559 and 560, Statutes of 2008) direct the state’s implementation of such green chemistry strategies. The US government, several states and cities, and industry are similarly exploring approaches for alternative analyses that can include hazard, risk, environmental, life cycle, and carbon impact assessments. A primary goal is a rapid and streamlined review and assessment to ensure the availability of safer and more effective products for the consumer and general public, at reduced costs and with minimal environmental impacts. Our panel of regulators and scientists from different sectors will explore approaches that can be used to implement green chemistry goals. It begins with a government perspective on challenges of development and implementation of legislation that will be effective, enforceable, and practical. This session features toxicity methods and case studies for hazard and risk-informed screening strategies utilizing high-throughput data, structure activity, and other toxicity information. It also considers how toxicity assessments can be utilized together with evaluations that account for carbon footprint and other impacts of product manufacture, use, and disposal for green chemistry decision making. At the conclusion of this session, two experts will lead a panel discussion and provide their exper-tise in exposure and risk assessment, regulatory policy decision-making, and occupational clinical medicine.
What’s the Buzz? Bee Health and California’s Agricultural Industry
Tuesday, March 13, 9:00 AM–11:45 AM
Chairperson(s): Moire R. Creek, Valent USA Corporation, Walnut Creek, CA, and Karen Steinmetz, SRI International, Menlo Park, CA.
Sponsor: Northern California Regional Chapter
There is a significant honey bee health crisis in California and globally that may threaten the future of California’s agricultural industry. Over half of California crops are dependent upon pollinators, including honey bees, with a potentially staggering economic impact approaching tens of billions of dollars. Some colonies collapse from the rapid loss of adult bees with the queen, a handful of bees, and some brood still present in the hive. In the US, this set of symptoms has been called Colony Collapse Disorder, or CCD. This condition is one component of a more general problem of colony losses, which has reached record highs in the past decade. Colony numbers in the US have been declining since the late 1940s because of the declining number of beekeepers. This trend continues but is now accelerated because of the challenge of keeping bees healthy and productive. Beekeeper surveys indicate annual colony losses of 30% and more. Multiple stressors, including Varroa and tracheal mites, Nosema, foulbroods diseases, numerous viruses, and small hive beetles, may be present in hives and can explain most of the colony losses. Other potential contributing factors are being investigated as well. Our panel brings together scientists, stakeholders, and regulators to discuss different viewpoints on the complex world of bees and what might be causing the honey bee health crisis. Pesticide testing methodologies and results will also be addressed. We will provide an overview on the current status of bee and colony health and an introduction into the multifactorial issues that affect bee health. This discussion will be followed by a presentation on the potential health threats posed by infectious agents. Next, a State of California representative will outline the steps being taken to protect bee health while balancing the need for agricultural crop protection tools. Finally, the complex approaches to understanding the relationship between pesticide residues and bee health and the logistical challenges of addressing these in a regulatory context will be discussed.
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