Asbestos Fate, Exposure,
Remediation, and
Adverse Health Effects
Director: Ian A. Blair, Ph.D.
Deputy Director: Trevor M. Penning, Ph.D.
NIEHS Grant: P42ES023720
Asbestos sites in EPA regions
Questions submitted to
CEET by Ambler community
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Can asbestos be remediated?
Is asbestos transported by water?
Why is there a cluster of mesotheliomas among
women in Ambler?
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?
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 BoRit 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
0min
10min
20min
30min
10μm
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
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1930 US Census
1930 US Life Tables
National Death Index
Data elements
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Age
Gender
Race
Occupation
Address
Exposures of interest
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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)
Bap1+/+
Bap1+/-
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 SV40 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
Mesothelioma
biomarker
Soluble mesothelinrelated peptides or
proteins
Fibulin 3
High mobility group
box 1
Abbrev
Description
SMRP
Mesothelin and SMRP are 40-kDa glycoproteins
from proteolytic cleavage of the 69-kDa mesothelin
precursor protein - both are analyzed.
None
HMGB1
A protein that belongs to a family of extracellular
proteins expressed in the basement membranes of
blood vessels.
HMGB1 is a chromatin protein. Unmodified protein
in nucleus - lysine hyperacetylation causes
translocation into the cytosol.
Sens Spec
(%)
(%)
Ref
50
70
Pass 2008
73
89
Pass 2012
34
Tabata 2013
100 Tababta
2013
Lipid 1
None
Lipid with molecular weight of 330 Da.
80
83
Present study
Lipid 2
None
Lipid with molecualr weight of 371 Da.
95
95
Present study
Lipid 3
None
Lipid with molecular weight of 373 Da.
90
95
Present study
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 BoRit 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
Assess research
 Practical
 Reasonable
 Implementable
Marketing
TDT
PIs of
Projects
Stakeholders
Program
Director
Metrics and
evaluations
Regulatory Agencies, CEC, Local
Government, Private/Public
Partnerships, Healthcare System
National Forum
Policy &
Practice
Patents
PCI
Interdisciplinary
Training Core
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
PhD Students in the Certificate Program
in Environmental Health Sciences *
PhD Students from the Masters in
Environmental Studies or Biology
Graduate Group**
Fall 1st Year
Introduction to Superfund Sites and Health Effects of Hazardous Waste PHRM/ENVS-627
Spring 1st Year
Research Methods Course ENVS 533
Molecular Toxicology PHRM 590
Summer 1st 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 2nd Year
ENVS Elective
Occupational and Environmental Health
PUBH 503
PhD from BGS Graduate Group
PhD from SAS Graduate Group
Approved By Biomedical Graduate Studies and School of Arts & Sciences
Fall 2014
Inter-Disciplinary Training Core
 Integrated Curriculum
-New Superfund Hazardous Waste and Adverse
Health Effects Course
 Optional Training Experiences
-Externships with USEPA
-Penn Center for Innovation Fellows Program
-Community Engagement
 Penn CEET/SRP Seminar Series
 Penn CEET/SRP Annual Symposium
Acknowledgements Penn SRP
Center