Penn researchers awarded $10 million grant to study adverse health effects, remediation of asbestos

Researchers at the Center of Excellence in Environmental Toxicology (CEET), Perelman School of Medicine at the University of Pennsylvania, have been awarded a $10 million grant from the National Institute for Environmental Health Sciences (NIEHS) over the next four years to study asbestos exposure pathways that lead to mesothelioma, the bioremediation of this hazardous material, and mechanisms that lead to asbestos-related diseases. One of these, mesothelioma, a rare cancer diagnosed in about 3,000 patients each year, is caused almost exclusively by exposure to asbestos. The disease is usually fatal with very poor prognosis once diagnosed.

The Penn Superfund Research and Training Program (SRP) Center, which was established by this grant, evolved as a direct consequence of concerns from the community living near the BioRit Asbestos Superfund site in Ambler, PA, about 20 miles north of Philadelphia. CEET is the academic home for the Penn Superfund Center.

NIEHS is a primary stakeholder in the SRP Center, with its sister Superfund programs at the U.S. Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry.

This award is the first NIEHS Superfund grant driven by problems identified in a community-academic partnership. CEET's Community Outreach and Engagement Core (COEC) has facilitated bi-directional communication with the Ambler community for the last five years. The communities of West and South Ambler have long been active in studying the ramifications of their town's long-closed asbestos factory. Residents in these communities remain at risk for environmental exposure and a potentially increased risk of developing mesothelioma. Ian A. Blair, PhD, professor of Pharmacology, is the director of the Center. CEET director Trevor M. Penning, PhD, professor of Pharmacology is the deputy director of the Center. Christine Shwed is the Center's administrative coordinator. Researchers from the Abramson Cancer Center (ACC), the Penn School of Arts and Sciences, and Fox Chase Cancer Center are also lead investigators on the grant.

"The work of the Superfund Center is a model of how to bring precision medicine into the realm of environmental health by determining, on an individual basis, who has been exposed to a toxicant and whether they will develop disease," says Penning.

"I am heartened that the NIEHS has chosen to fund this truly interdisciplinary center, which is uniquely qualified to address the concerns relating to asbestos exposure that have been identified by the Ambler community," notes Blair.

"This new research and training award is designed to address important asbestos-related issues so that more informed risk and clean-up decisions can be made and shared," said NIEHS Superfund research program director William Suk, PhD. "This funding of the Penn SRP Center has the potential to help communities affected by asbestos exposures locally and elsewhere."

Long-term Solutions for a Long-term Problem

From the late 1880s through the present day, Ambler residents have had either occupational or environmental exposure to asbestos. As a result, both current and former residents of the area face potentially serious long-term health consequences. The Pennsylvania Department of Health, with the aid of the COEC, determined that there has been an increase in the rate of mesothelioma in the area compared to the adjacent zip codes, with women having a greater risk than men. The researchers are hopeful that continued investigation and education will yield more information about exposure pathways that led to these health risks.

The new Center will tackle two inter-related environmental science studies and four biomedical science studies. The six projects were designed to address a community-based question or concern that been previously identified by the COEC:

• Can we remediate asbestos without moving it from the original disposal site?

• What do we know about the fate and transport of asbestos in the environment by water and air?

• What do we know about the exposure pathways that were responsible for the mesothelioma cluster in Ambler? And why is the incidence higher in women?

• Is susceptibility to mesothelioma genetic?

• Can asbestos-related disease be prevented?

• Is there a blood test to determine whether a person will get asbestos-related disease?

"The new SRP Center is a great example showing the value of Penn's Environmental Health Sciences Core Center's community outreach and engagement activities," notes NIEHS Core Center program director Claudia Thompson, PhD. "CEET includes two-way communication that spurs new research opportunities to address environmental public health concerns of community residents."

The environmental projects centering on the remediation of asbestos particles will be conducted by Jane Willenbring, PhD and Brenda Casper, PhD (School of Arts and Sciences) and will use mycrorrhiza fungi to break down asbestos to a new non-toxic mineral form. Studies on the mobility and fate of asbestos particles in streams and rivers will be conducted by Doug Jerolmack, PhD (School of Arts and Sciences) and Willenbring. Methods to detect asbestos in the environment will involve monitoring its movement through soil and water using translucent soil substitutes and a nanoaqaurium. A sociological study to identify how asbestos exposure can occur and whether this can explain the cluster of asbestos-induced mesotheliomas in Ambler will be conducted by Fran Barg and Ted Emmett (Penn Medicine).

Although these projects evolved in response to the Ambler community's concerns, the results could be readily translated to the 15 other Superfund asbestos sites in the US.

The biomedical arm of the Center grant will explore the genetics of mesothelioma susceptibility and develop a blood test for early detection using a mouse model of mesothelioma. Becky Simmons, PhD (Penn Medicine) will be working with Joseph Testa, PhD (Fox Chase) and a tumor-suppressor knockout mouse he has developed. The team will determine if there is genetic predisposition that makes individuals more susceptible to asbestos-induced mesothelioma. The mouse model can be used to test whether the remediated asbestos is less toxic. Melpo Christofidou-Solomidou, PhD, and Steve Albelda, MD (Penn Medicine) will study how to prevent mesothelioma in mice exposed to asbestos using an antioxidant in flaxseed and also use the flaxseed to treat the mice if they have early signs of mesothelioma. Anil Vachani and Blair will develop a blood test to determine if subjects have been exposed to asbestos and whether they are at risk for developing mesothelioma. In order to do this, they will use blood samples from workers who were heavily exposed to asbestos. These samples will be provided by the National Center for Vermiculite and Asbestos Related Cancer at Wayne State University and by the Philadelphia Insulators and Asbestos Workers Local 14 Union. The mesothelioma blood samples will be provided by the Penn Lung Center and the Mesothelioma and Pleural Program, the National Mesothelioma Virtual Bank, and stored mesothelioma samples held at the Mt. Sinai Medical School in New York.

The Biostatistics Research Core directed by Wei-Ting Wang, PhD (Penn Medicine) will provide the biostatistical expertise for all of the projects and the Research Translational Core directed by Richard Pepino, MSS, and Robert Schenkel, PhD (Penn Center for Innovation) will transmit results of the Center's activities to the scientific community, regulatory agencies and promote such new technologies as asbestos remediation strategies for commercialization, as well as new prognostic and diagnostic tests for asbestos exposure. The Community Engagement Core directed by Emmett and Barg will transmit all of the findings back to the Ambler community, as well as relaying additional community concerns to Center investigators.

"The new Superfund Center, with its focus on asbestos fate, exposure, remediation, and adverse health effects will significantly complement a Translational Center of Excellence in Thoracic Oncology that has been established within the Abramson Cancer Center," notes Chi Van Dang, MD, PhD, ACC director. "It will also enrich the Population Sciences Program of the Cancer Center, with its mission of cancer risk assessment."

"I am delighted that the new Center has been established because it will significantly add to Penn's translational research portfolio," noted Garret FitzGerald, MD, FRS, director of Penn's Institute for Translation Medicine and Therapeutics. The grant also provides funds to establish a unique interdisciplinary training program, which will marry environmental sciences with environmental health sciences so that doctoral students and postdoctoral fellows will receive training in these complementary disciplines. Unique features of this training include participation in Superfund webinars sponsored by NIEHS and internships in technology transfer at CTT and the EPA.

Source: University of Pennsylvania School of Medicine