Fall 2013 Seminar Schedule.

Join us every Friday from 12 to 1 p.m. in BUSM L210.

Modern Exposure Science: The Exposome, Complex Mixtures, and Vulnerable Populations

September 6

Emma Virginia Preston, MPH and James Watt, MS
Doctoral Students, Department of Environmental Health, SPH

Seminar Summary: This seminar will provide an introduction to concepts and challenges in modern exposure science, and an overview of this year’s seminar. Topics will include the “Exposome,” complex mixtures, new methodologies, and implications for vulnerable populations.

Readings:
  • Rappaport SM (2011) Implications of the exposome for exposure science. Journal of Exposure Science and Environmental Epidemiology 21:5-9.

Exposure Science: The Value of Pursuing both External and Internal Markers of Exposure

September 13

Paul Lioy, PhD
Professor and Vice Chair, Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School
Deputy Director of Government Relations and Director of Exposure Science, at the Rutgers Environmental and Occupational Health Sciences Institute
Vice Chair: National Academy of Sciences Committee on Human and Environmental Exposure Science in the 21st Century

Seminar Summary: The NRC recently published the report “Exposure science in the 21st century,” which will provide a backdrop for the seminar. The seminar will highlight some of the main features of the report, and some of the opportunities associated with the field. It will also discuss how and where the Exposome concept fits within the fabric of the field, and the need for both internal and external markers of exposure.

Readings:
  • Lioy, P.J. (2010) Exposure Science: A View of the Past and Major Milestones for the Future. Environment Health Perspectives. 118, 1081-1090. http://dx.doi.org/10.1289/ehp.091634 PMID: 20308034
  • Lioy, P.J. and Smith, K. A. (2013) Discussion of Exposure Science in the 21st Century: a Vision and a Strategy, Environmental Health Perspectives, 121,405-409, http://dx.doi.org/10.1289/ehp.1206170 PMID: 23380895
Additional background readings:
  • Lioy, P.J. and Vallero, D.A. (2010) The Scientific Method in an Era of Advocacy,Ethics in Biology, Engineering and Medicine. 1(4): 293-318. http://dx.doi.org/10.1615/EthicsBiologyEngMed.v1.i4.70
  • Lioy, P.J. and Georgopoulos, P.G. (2011) New Jersey: A Case Study of the Reduction in Urban and Suburban Air Pollution from the 1950s to 2010. Environmental Health Perspectives, 119 (10): 1351-5.http://dx.doi.org/10.1289/ehp.1103540 PMID: 21622086
  • Lioy, P.J. and Rappaport S.M. (2011) Exposure science and the exposome: an opportunity for coherence in the environmental health sciences. Environmental Health Perspectives, 119 (11): A466-7. http://dx.doi.org/10.1289/ehp.1104387 PMID: 22171373

Mixture Studies in the Laboratory: Approaches to Studying Multifaceted Exposures to Nuclear Receptor Ligands

September 27

Jennifer Schlezinger, PhD
Department of Environmental Health, SPH

Seminar Summary: Exposure to mixtures of toxicants, rather than a single toxicant is the norm, rather than the exception. How do we assess the effects of complex exposures in laboratory experiments? How do we determine if there is an additive effect of the mixture or a synergistic effect? Our ability to assess effects of mixtures relies upon our knowledge of the biological target of the toxicants and our ability to characterize the effects of individual toxicants. Using a simple receptor, the aryl hydrocarbon receptor, we developed a mathematical model (generalized concentration addition) to predict the effect of multi-ligand exposures. We validated the mathematical model with data generated from assessment of aryl hydrocarbon receptor transcriptional activity. Key questions remain, however. Will the model predict the behavior of a more complex receptor? Will the model predict not only early receptor mediated events (i.e. receptor-mediated transcription) but also downstream biological effects (i.e. cellular differentiation)? In order to address these questions, we are expanding our approach to a second receptor, the peroxisome proliferator activated receptor gamma (PPARγ). We are developing a mathematical model of receptor activation in the presence of multiple ligands, as well as testing the validity of the model using both transcriptional activation and biological function (lipid accumulation) data. Last, complex exposures are not necessarily to two chemicals, but rather can consist of a chemical and a stressor. We are examining a complex exposure of to a PPARγ ligands and a stressor (high fat diet) in vivo.

Readings:
  • Howard GJ, Schlezinger JJ, Hahn ME, Webster TF. Generalized Concentration Addition Predicts Joint Effects of Aryl Hydrocarbon Receptor Agonists with Partial Agonists and Competitive Antagonists.Environ Health Perspect. 2010; 118(5):666-672
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866683/
  • Yanik SC, Baker AH, Mann KK, Schlezinger JJ. Organotins are potent activators of PPARγ and adipocyte differentiation in bone marrow multipotent mesenchymal stromal cells. Toxicol Sci. 2011 Aug;122(2):476-88.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155090/

How to Add: Perspectives in Toxicology & Epidemiology Regarding Complex Mixtures and Exposures

October 4

Tom Webster, DSc
Department of Environmental Health, SPH

Seminar Summary: Epidemiologists have quite different ideas about how to analyze “interactions” from toxicologists and pharmacologists. This seminar will compare and contrast the two approaches and discuss some ideas for using toxicological ideas in epidemiology.

Readings:

Traffic-related Particulate Complex Mixtures Induce Distinctive Outcomes in the Respiratory and Cardiovascular Systems

October 18

John Godleski, MD
Associate Professor, Department of Environmental Health, Harvard School of Public Health

Seminar Summary: Our laboratory has developed a system to study primary and secondary particulate derived exclusively from mixed vehicular traffic. Traffic-derived aerosols are drawn from the plenum of a major traffic tunnel into a large dynamic reaction chamber with lights to simulate sunlight for production of secondary organic aerosol. After reaction, the aerosol at a target dose of 50 micrograms per cubic meter is drawn directly into animal exposure chambers for a 5 hr/day acute or subchronic exposures. This relatively low dose has produced distinctive and significant respiratory and cardiovascular health effects. Furthermore, the traffic pattern is sufficiently stable and reproducible for use in repeated mechanistic studies.

Readings:

Complex Exposures / Complex Responses: Understanding Chemical Impacts on Natural Populations

October 25

Mark Hahn, PhD
Department Chair Biology, Senior Scientist, Woods Hole Oceanographic Institution (WHOI)

Seminar Summary: Organisms inhabiting the New Bedford Harbor, a federal Superfund site, are exposed to a complex mixture of polychlorinated biphenyls (PCBs), other organic pollutants, heavy metals, and other types of stressors such as hypoxia. This presentation will explore the response of one species, the Atlantic killifish Fundulus heteroclitus, to this complex exposure. The focus will be on signaling pathways through which fish (and humans!) deal with environmental chemicals and the molecular interactions (“cross-talk”) among these pathways that help determine the response to these complex exposures.

Readings:
  • Oleksiak, M. F., Karchner, S. I., Jenny, M. J., Franks, D. G., Mark Welch, D. B., and Hahn, M. E. (2011). Transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor (AHR) agonist in embryos of Atlantic Killifish (Fundulus heteroclitus) from a Marine Superfund Site. BMC Genomics 12, 263. http://www.biomedcentral.com/1471-2164/12/263
  • Harbeitner, R. C., Hahn, M. E., and Timme-Laragy, A. R. (2013). Differential sensitivity to pro oxidant exposure in two populations of killifish (Fundulus heteroclitus). Ecotoxicology (London, England) 22, 387–401. 

Improving Environmental Management in Peru: An Introduction

November 1

Rossana Rivas
Project Manager, Biomedical Engineering, Innovation and Technology Management for the Office of the Presidency/Vice-presidency for Research Office, Pontifical Catholic University of Peru-PUCP
Professor and Researcher: School of Engineering & Sciences, Biomedical Engineering Master Program, Social Management Master Program, Pontifical Catholic University of Peru-PUCP; Health Public School, Policy and Management Master of Science Technology and Innovation, Universidad Peruana Cayetano Heredia-UPCH
Co-Founder & Executive Director- Health Technopole CENGETS PUCP, Cluster of Health Technology Management and Clinical Engineering

Seminar Summary: Peru experienced in recent years “socio-environmental conflicts” because of the increased mining activity, raising concerns among the population, mainly because the land used for its operations was the same used ancestrally by the Communities. It is noteworthy that the population is characterized by: high level of illiteracy, agricultural activities, location high above the sea level. Regarding environmental pollution, their main concern is around water and land, basic resources for their livelihoods. The risk of heavy metal pollution both in Lima and in the Andean region has become a priority for the Government’s attention. The actions in this regard are insufficient however. Two cases are presented, one in the north of Lima and one in Espinar province of Cusco. Some factors to consider in the process of a necessary change are: i) improvement of environmental policy design from the government; ii) capacity development; iii) technology transfer; iv) promotion of research.

Fetal Alcohol Syndrome in the Western Cape, South Africa: Multiple exposures in a particularly vulnerable population, and what to do about it?

November 8

Leslie London, MD
Professor, School of Public Health and Family Medicine, University of Cape Town, and Associate Director of the Centre for Occupational and Environmental Health Research, University of Cape Town

Seminar Summary: Rural farming communities in the Western Cape province of South Africa are a vulnerable community who experience a diversity of hazardous exposures. One particular phenomenon that captures this conundrum is that of Fetal Alcohol Syndrome (FAS). FAS has been reported in 5 to 10% of school-going children in the province, which are rates that are the highest in the world, much higher than even so-called high-risk populations in North America. The direct antecedent of FAS, alcohol consumption in pregnancy, is itself a product of multiple behavioral, social and historical factors related to alcohol consumption by workers in agriculture in the region. However, consumption of alcohol during pregnancy may not be sufficient to explain these tremendously high rates, since the alcohol consumption of Western Cape mothers with FAS children is not as high as in other high-risk populations. There may thus be other factors common in this population which contribute individually, or synergistically, to increased risk of intra-uterine damage. Candidate exposures include pesticides, smoking and toxic contaminants within cheap wine drunk in the Western Cape, and genetic and nutritional deficits may also interact in the genesis of a public health calamity of this scale. Understanding the etiology of the FAS epidemic in its fullest dimensions in the Western Cape, using the full range of exposure science characterization, is critical to successful interventions to reduce the burden of disease due to FAS in the region, particularly given that community-based interventions and upstream public health policies are likely to be the mainstay of FAS prevention.

Readings:
Additional Readings:
  • Morojele NK, London L, Olorunju SA, Matjila J, Davids AS, Rendall-Mkosi KM. Predictors of Risk of Alcohol-Exposed Pregnancies among Women in an Urban and a Rural Area of South Africa. SocSci Med 2010; 70: 534-42.
  • May PA, Gossage JP, Marais AS, et al. The epidemiology of fetal alcohol syndrome and partial FAS in a South African community. Drug Alcohol Depend. 2007 May 11; 88(2-3):259-71.
  • Rendall-Mkosi K, London L, Adnams C, Morojele N, McLoughlin J, Goldstone C. Fetal Alcohol Spectrum Disorder in South Africa: Situational and Gap Analysis. Unicef, Pretoria, March 2008. http://www.unicef.org/southafrica/SAF_resources_fetalalcohol.pdf
  • London L. Alcohol consumption amongst South African farm workers: a post-apartheid challenge. Drug and Alcohol Dependence 2000; 59: 199-206.Topic: Differentiating the Impacts of Alcohol and Alcohol Contaminant Exposures in Promoting Fetal Alcohol Syndrome

Attenuation of X-ray-induced Germ Cell Apoptosis in a Rat Model of Co-exposure Testicular Toxicity

November 15

Kim Boekelheide, MD, PhD
Professor of Medical Science, Pathology & Laboratory Medicine, Brown University

Seminar Summary: Testicular effects of toxicant mixtures may differ from those of the individual constituents. We have assessed the co-exposure effects of the model germ cell- and Sertoli cell-specific toxicants, x-ray and 2,5-hexanedione, respectively. At high doses, 2,5-hexanedione co-exposure attenuated x-ray-induced germ cell apoptosis; however, the protective effect of co-exposure at lower, more environmentally relevant exposure levels was lost. Thus, there are complicated dose-dependent and target cell-dependent interactions that influence co-exposure effects.

Readings:
  • Suppression of radiation-induced testicular germ cell apoptosis by 2,5-hexanedione pretreatment. I. Histopathological analysis reveals stage dependence of attenuated apoptosis. Yamasaki H, Sandrof MA, Boekelheide K. Toxicol Sci. 2010 Oct;117(2):449-56 http://toxsci.oxfordjournals.org/content/117/2/449.full.pdf+html

Interrogating the Exposome to Discover Causes of Chronic Diseases

Special Thursday Seminar:
December 5

Stephen M. Rappaport, PhD
Professor of Environmental Health, University of California, Berkeley

Seminar Summary: Since 2001 most researchers have investigated the genome to discover causes of chronic diseases. But evidence points to the exposome (representing all exposures) as being the major contributor to these diseases. Current technology permits untargeted exposome-wide-association studies (EWAS) to identify causal exposures. Then targeted follow-up investigations can pursue exposure sources, dose-response and disease mechanisms.

Readings:

EH Doctoral Student Presentations

December 6

Lindsay Underhill, MPH
Doctoral Student, Department of Environmental Health, BUSPH
How Can Simulation Modeling Predict the Health and Economic Impacts of Energy Efficient Design? A Case Study of Multifamily Housing in Boston, MA

Judy Ou, MPH
Doctoral Student, Department of Environmental Health, BUSPH
Social & Environmental Determinants of Physical Activity: Results & Lessons Learned