Asbestos Fate, Exposure, Remediation, and Adverse Health Effects Director: Ian A. Blair, Ph. D. Deputy Director: Trevor M. Penning, Ph. D. NIEHS Grant: P 42 ES 023720
Asbestos sites in EPA regions
Questions submitted to CEET by Ambler community • • • Can asbestos be remediated? • Is there a genetic pre-disposition to asbestosinduced mesothelioma? • Can asbestos-induced mesothelioma be prevented? • Is it possible to develop blood tests for asbestos exposure and mesothelioma? Is asbestos transported by water? Why is there a cluster of mesotheliomas among women in Ambler?
Penn SRP Projects & Cores
Penn SRP Center Web Site http: //www. med. upenn. edu/asbestos/
Project 1: Remediation of Asbestos Particles Co-PIs: Jane Willenbring and Brenda Casper (School of Arts and Sciences, University of Pennsylvania) Hypothesis: it will be possible to discover and quantify new, better ways to remediate asbestos sites in situ using a combination of hyper-accumulating plants and plants native to naturally metal rich serpentine soils coupled with their associated arbuscular mycorrhizal fungi (AMF)
Soil Sampling at Bo. Rit Site Soil for capping
Bioremediation: Conceptual Processes
Project 2: Mobility and Fate of Asbestos in Water Co-PIs: Douglas J. Jerolmack and Jane Willenbring (School of Arts and Sciences, University of Pennsylvania) Hypothesis: the mobility of asbestos particles in groundwater has been underestimated, and the unusually large aspect ratio and material properties make asbestos transport significantly different from other fine particles
Real-time observations of dynamics and aggregate formation of asbestos in water 0 min 10 min 20 min 30 min 10μm
Trajectories of asbestos particles in water
Project 3: Social and Spatial Determinants of Asbestos Risk in a Superfund EJ Community Co-PIs: Frances Barg and Edward A. Emmett (Perelman School of Medicine, University of Pennsylvania) Hypothesis: The incidence of mesothelioma is related to occupational and non-occupational exposures in the Ambler area, to the proximity to the site, and to various social, lifestyle and economic factors
Materials and Methods Retrospective cohort study Data • • • 1930 US Census 1930 US Life Tables National Death Index Data elements • • • Age Gender Race Occupation Address Exposures of interest • • • Occupational exposure Paraoccupational exposure Environmental exposure
Project 4: Integrated Models of Malignant Mesothelioma Co-PIs: Joseph R. Testa (Fox-Chase Cancer Center) and Rebecca Simmons (Perelman School of Medicine, University of Pennsylvania) Hypothesis: Mutations in key tumor suppressor genes as well as epigenetic modifications, represent key molecular changes in mesothelial cell physiology that collectively contribute to mesothelioma formation following exposure to asbestos. The identification and characterization of such alterations may afford novel opportunities for early diagnosis, prevention and therapy.
Survival Accelerated mouse models of asbestos-induced malignant mesothelioma (MM) Bap 1+/+ Bap 1+/- Weeks post initial asbestos exposure
Project 5: : Chemoprevention of Asbestos-Induced Malignant Mesothelioma Co-PIs: Melpo Christofidou-Solomidou and Steven M. Albelda (Perelman School of Medicine, University of Pennsylvania) Hypothesis: Secoisolariciresinol diglucoside (SDG) will interfere with inflammasome activation and ROS generation in asbestos-activated macrophages and mesothelial cells and thus interfere with initiation and propagation of damaging processes that would ultimately lead to mesothelioma formation
Flaxseed lignan complex (FLC) in mouse models
Effect of FLC on SV 40 TAg mice
Project 6: Biomarkers of Asbestos Exposure Co-PIs: Ian A. Blair and Anil Vachani (Perelman School of Medicine, University of Pennsylvania) Hypothesis: Unsupervised serum metabolomics analysis using ultra-high resolution Liquid Chromatography-Mass Spectrometry will reveal novel biomarkers of biological response to asbestos that can be characterized
A new approach to discovery of mesothelioma biomarkers Asbestos exposed (n=40) Mesothelioma (n=40)
Mesothelioma biomarkers: summary Tabata 2013
Penn SRP Center Cores · Administrative · Community Engagement · Research Translation · Biostatistics Research · Inter-Disciplinary Training Core
Community Engagement Core Co-PIs: Edward Emmett and Fran Barg (Perelman School of Medicine, University of Pennsylvania) Hypothesis: Concerns of the community can be translated into research projects
Penn SRP Center: local impact
Penn SRP Center: Biomarkers and Ambler Bo. Rit site
Research Translation Core Co-PIs: Richard Pepino and Robert Schenkel (Perelman School of Medicine, University of Pennsylvania) Hypothesis: The knowledge and discoveries of the Center can be translated into actionable items that will remediate asbestos waste (Projects 1 and 2) and reduce its adverse health effects (Projects 3 -6) by forging productive partnerships with the public and private sectors
Research Translation Core Committee Members – Technology Development & Transfer (TDT) includes. . . • Richard Pepino, Ian Blair, Trevor Penning, Robert Schenkel (PCI), Jane Willenbring (Project 1 PI), David Mandelbaum (Superfund Attorney), Sachin Shankar (PA-DEP), Deborah Burgin (ATSDR, HQ) William Hagel (EPA, ORD), and Samantha Beers (EPA, EJ) – Research Translation & Application (RTA) includes. . . • Richard Pepino, Marilyn Howarth, Douglas Jerolmack (Project 2 PI), Francis Barg (CEC), Lora Werner (ATSDR), Charlie Root (EPA /OSC), Jill Lowe (EPA/Ambler Supervisor), Josh Barber EPA/OSC), Barbara Allerton (PADOH), and Catherine Klinger Kutcher (Philadelphia DOH)
TDT and RTA Committee roles in technology transfer Inventions and patents Recommendations Target opportunities Develop metrics Policy issues Regulation changes Legislative fixes Risk assessment protocols RTA TDT PIs of Projects Stakeholders Patents PCI Program Director Metrics and evaluations Regulatory Agencies, CEC, Local Government, Private/Public Partnerships, Healthcare System Assess research Practical Reasonable Implementable Marketing Interdisciplinary Training Core National Forum Policy & Practice Products Process Best Management Practices Removal Investigation/ Feasibility Studies Risk Assessment
Inter-Disciplinary Training Core Co-PIs: Trevor M. Penning and Jane Willenbring (Perelman School of Medicine, University of Pennsylvania) Mission. The Interdisciplinary Superfund Research Training Program provides cross-training in environmental science and environmental health science to ensure that all trainees master the necessary skills and have a sufficient knowledge base to understand the hazards of superfund waste sites and use this knowledge to help remediate these sites and their ensuing health effects.
Inter-Disciplinary Training Core Ph. D Students in the Certificate Program in Environmental Health Sciences * Ph. D Students from the Masters in Environmental Studies or Biology Graduate Group** Fall 1 st Year Introduction to Superfund Sites and Health Effects of Hazardous Waste PHRM/ENVS-627 Spring 1 st Year Research Methods Course ENVS 533 Molecular Toxicology PHRM 590 Summer 1 st Year Summer: EP 811 and EP 812 Introductory Epidemiology and Biostatistics (Summer Rotation-Field Work or Capstone Project with Community Engagement) (Summer- Rotation –Biomedical Research) Fall 2 nd Year ENVS Elective Occupational and Environmental Health PUBH 503 Ph. D from BGS Graduate Group Ph. D from SAS Graduate Group Approved By Biomedical Graduate Studies and School of Arts & Sciences Fall 2014
Inter-Disciplinary Training Core q Integrated Curriculum -New Superfund Hazardous Waste and Adverse Health Effects Course q Optional Training Experiences -Externships with USEPA -Penn Center for Innovation Fellows Program -Community Engagement q Penn CEET/SRP Seminar Series q Penn CEET/SRP Annual Symposium
Acknowledgements Penn SRP Center
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