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Exposures and Latent Disease Risk: Session II - Identifying Hallmarks and Key Characteristics

Sponsored by: NIEHS Superfund Research Program

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The NIEHS Superfund Research Program (SRP) is hosting a Risk e-Learning webinar series focused on understanding the health effects of exposures when there is a lag between exposure and the onset of the disease. In the second session, presenters will discuss new methods to better understand potential disease risk by identifying key characteristics or hallmarks of chemicals and disease. This research may provide insight into identifying chemicals that may lead to disease earlier on in the disease progression and help explore how aging itself can be a risk factor for disease.

Martyn Smith, Ph.D., director of the University of California, Berkeley SRP Center, will describe the key characteristics approach to helping identify chemicals that cause cancer and other adverse outcomes. In evaluating whether a chemical can cause cancer or another adverse outcome, three lines of evidence are typically considered: epidemiology, animal bioassays, and mechanistic evidence. The key characteristics (KC) form the basis of a uniform approach for searching, organizing, and evaluating mechanistic evidence to support hazard identification without the need for a deductive hypothesis. KCs are the established properties of the chemicals and have been developed for carcinogens, endocrine disruptors, reproductive and neuro-toxicants, and are becoming increasingly used by authoritative bodies and regulatory agencies.

Michelle La Merrill, Ph.D., associate professor at the University of California, Davis, will focus on using the key characteristics of endocrine disruptors to organize mechanistic support of the developmental basis of endocrine disruption. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing health risks, such as for cancer, reproductive impairment, cognitive deficits, and obesity. Inspired by work to improve hazard identification of carcinogens using KCs, they have developed 10 KCs of EDCs based on our knowledge of hormone actions and EDC effects. This presentation will reveal how these 10 KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs that contribute to developmental vulnerability to adult disease, and use DDT and bisphenol A as examples to illustrate this approach.

Ron Kohanski, Ph.D., deputy director of the Division of Aging Biology at the National Institute on Aging, will focus on aging as a risk factor for disease. Geroscience is a recently evolved field of research on the intersection between the biology of aging and the biology of disease. The geroscience hypothesis states that "slowing the rate of aging will delay the onset and decrease the severity of chronic diseases and comorbidities that primarily impact older people." This does not mean that old age per se is a risk factor, any more than claiming that childhood is a risk factor for diseases that primarily afflict children. However, in the latter case the underlying causes may be the stage of development does not yet confer resilience against pathogens, for example. In the former case, the underlying causes may be loss of that resilience (acquired over a lifetime) from the failure of underlying molecular networks that maintain the body and adapt to environmental changes. This talk will present a viewpoint that aging can be treated as a risk factor, attempting to show that both the magnitude and duration of changes that are the process of aging can be altered in ways that are either beneficial or detrimental to health.

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It is EPA's policy to make reasonable accommodation to persons with disabilities wishing to participate in the agency's programs and activities, pursuant to the Rehabilitation Act of 1973, 29 U.S.C. 791. Any request for accommodation should be made to at or , preferably one week or more in advance of the webinar, so that EPA will have sufficient time to process the request. EPA would welcome specific recommendations from requestors specifying the nature or type of accommodation needed. Please note that accommodation requests for closed captioning are not necessary. Closed captioning is being provided for all CLU-IN webinars as of October 1, 2016.

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Content Disclaimer

This webinar is intended solely to provide information to the public. The views and opinions expressed as part of this webinar do not necessarily state or reflect those of the U.S. Environmental Protection Agency. It is not intended, nor can it be relied upon, to create any rights enforceable by any party in litigation with the United States, or to endorse the use of products or services provided by specific vendors. With respect to this webinar, neither the United States Government nor any of their employees, makes any warranty, express or implied, including the warranties of merchantability and fitness for a particular purpose, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights.

Presenters:

Martyn Smith, Ph.D.Martyn Smith, Ph.D., University of California, Berkeley SRP Center (martynts@berkeley.edu or 510-642-8770)
Martyn Smith, Ph.D., is a professor of toxicology and the Kenneth Howard and Marjorie Witherspoon Kaiser Endowed Chair in Cancer Epidemiology at the University of California, Berkeley. Smith is a laboratory scientist with expertise in molecular epidemiology, toxicology, and genomics, and his research is aimed at finding the causes of chronic diseases, including cancer and diabetes. Smith has led the Superfund Research Program (SRP) Center at Berkeley since its inception in 1987. This Center has been peer-reviewed and renewed 6 times and is funded at approx. $2.15m per annum, making it one of the largest NIH grants on the Berkeley campus. The UC Berkeley SRP Center focuses on exposures to high priority chemicals commonly found at Superfund sites, including arsenic, benzene, trichloroethene, formaldehyde, and polycyclic aromatic hydrocarbons to address the specific mandates of the Program. They take a novel approach to adopt the 'exposome paradigm' in research. This new paradigm, which Smith's team helped develop, allows for a 'seeing the whole picture' approach to risk assessment, hazard identification and the safe and effective remediation of hazardous sites containing multiple chemicals. In the exposome paradigm, all nongenetic environmental stressors are considered as environmental exposures. Therefore, cumulative risk assessment, where the impact of all stressors on a population is assessed, could be operationalized by exposomics. Communities living near sites face cumulative risks from a variety of environmental and social factors. The theme of the Center is, therefore, the exposome and the team proposes a step-wise approach to applying exposomics to help solve the complex problems found at Superfund sites.

Smith currently teaches toxicology and health risk assessment and mentors graduate students and postdoctoral scholars in the molecular toxicology, epidemiology and environmental health science programs. He has mentored dozens of graduate students and post-docs in his 36 years at UC Berkeley. Smith is a Fellow of the American Association for the Advancement of Science. He received the 2010 Children's Environmental Health Network Award, became an Elected Fellow of the Collegium Ramazzini in 2012, and received the Alexander Hollaender Award from the Environmental Mutagenesis and Genomics Society in 2014.


Michele La Merrill, Ph.D.Michele La Merrill, Ph.D., University of California, Davis (mlamerrill@ucdavis.edu or 530-754-7254)
Michele La Merrill, Ph.D., is an associate professor in the department of environmental toxicology in the college of agricultural and environmental sciences at the University of California, Davis. The mission of La Merrill laboratory is to understand the mechanistic basis of environmental causes of endocrine diseases: obesity, diabetes, hypertension, and breast cancer. Endocrine diseases are increasingly common and contribute to the leading causes of death worldwide, which are cardiovascular disease and cancer. They conduct cellular, whole animal and human epidemiological studies to integrate human observations with mechanistic investigations.

La Merrill earned her Ph.D. in Toxicology at the University of North Carolina at Chapel Hill through the mentorship of David Threadgill, Ph.D., and Linda Birnbaum, Ph.D., on the interaction of prenatal dioxin exposure and high fat diet on mammary cancer and metabolic syndrome risk. La Merrill earned her M.P.H. in epidemiology during her postdoctoral fellowship at Mount Sinai School of Medicine in New York City. There she conducted research on the influence of perinatal exposures and epigenetics on metabolic abnormalities in humans and rodents. She began research as an assistant professor in environmental toxicology at UC Davis in January 2013. She is a member of the Pharmacology & Toxicology Graduate Group, the Integrative Genetics and Genomics Graduate Group, Epidemiology Graduate Group, the UC Davis Genome Center and the UC Davis Comprehensive Cancer Center. She is also an adjunct professor in the Division of Environmental Genomics and Systems Biology at the Lawrence Berkeley National Lab.


Ron Kohanski, Ph.D.Ron Kohanski, Ph.D., NIH National Institute on Aging (kohanskir@mail.nih.gov or 301-496-6402)
Ron Kohanski, Ph.D., is the deputy director of the Division of Aging Biology at the National Institute on Aging, NIH. Trained as a biochemist, he obtained a Ph.D. in biochemistry from the University of Chicago in 1981. After a postdoctoral fellowship with M. Daniel Lane at the Johns Hopkins University School of Medicine, he held a faculty position at the Mount Sinai School of Medicine for 17 years before returning as a faculty member at Johns Hopkins. His fields of research included enzymology and developmental biology of the insulin receptor. Kohanski joined the Division of Aging Biology, NIA in 2005 as a Program Officer, and became Division Deputy Director in 2007. He has promoted aging research in the specific areas of stem cell biology and cardiovascular biology. More broadly, he promotes research efforts to expand studies beyond laboratory animals to address the basic biology of aging explicitly in human populations and non-laboratory animals (domestic and wild populations).

Kohanski is also a co-founder and co-leader of the trans-NIH Geroscience Interest Group (GSIG). The group spans the entire NIH and is built on the fact that aging is the major risk factor for most chronic age-related diseases. In keeping with this program, he has encouraged researchers to consider age as an essential parameter of research using animal models of chronic diseases. More broadly, he promotes research into the basic biology of aging that could explain why aging is itself the major risk factor of chronic diseases.


Moderators:

Heather Henry, Ph.D.Heather Henry, Ph.D., Superfund Research Program, National Institute of Environmental Health Sciences (henryh@niehs.nih.gov or 984-287-3268)
Since 2006, Heather Henry, Ph.D., has been a program administrator for the NIEHS SRP in Research Triangle Park, North Carolina. Her responsibilities include administration of the SRP Multi-Project Center Grants (P42), the SRP Individual Research Project Grants (R01), and the Small Business / Technology Transfer Grants (R41/42; R43/44). She earned a B.S. in Biological Sciences (Ecology and Evolution) at the University of Rochester, Rochester, NY; a Ph.D. in Biological Sciences at the University of Cincinnati, Cincinnati, OH; and completed a Fulbright Fellowship (post-doctoral) at the University of Melbourne and the University of Adelaide in Australia.


Jean BalentJean Balent, U.S. EPA Technology Innovation and Field Services Division (balent.jean@epa.gov or 703-603-9924)
Ms Balent is on the staff of the EPA's Technology Innovation and Field Services Division where she has worked to collect and disseminate hazardous waste remediation and characterization information since 2003. Ms Balent manages the Clean Up Information Network website and actively supports online communication and collaboration resources available to EPA. She formerly worked with the US Army Corps of Engineers Environmental Engineering Division in the Buffalo District. Ms Balent was also a member of the SUNY-Buffalo Groundwater Research Group where she constructed and tested large scale models of groundwater flow. Ms Balent has also conducted research relating to the Great Lakes, environmental remediation, and brownfields re-development. She holds a Bachelor's degree in environmental engineering from SUNY-Buffalo and a Master's degree in Information Technology from AIU.


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 May 28, 2020: Exposures and Latent Disease Risk: Session II - Identifying Hallmarks and Key Characteristics

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Rehabilitation Act Notice for Reasonable Accommodation

It is EPA's policy to make reasonable accommodation to persons with disabilities wishing to participate in the agency's programs and activities, pursuant to the Rehabilitation Act of 1973, 29 U.S.C. 791. Any request for accommodation should be made to at or , preferably one week or more in advance of the seminar, so that EPA will have sufficient time to process the request. EPA would welcome specific recommendations from requestors specifying the nature or type of accommodation needed, such as closed captioning.



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