As a direct response to local community concerns, Dr Ian A Blair and Protect and serve: colleagues at the Penn SRP Center are using federal funds to study asbestos exposure pathways that lead to asbestos-related diseases. Dr Blair hopes to identify biomarkers of asbestos exposure with the aim of community-driven assessing an individual’s risks of developing asbestos-related diseases.
he Center of Excellence in made up of microscopic fibrils, easily shed Environmental Toxicology (CEET), as the material is worked or degraded and superfund science part of the Perelman School of readily inhaled deep into the lungs. Its Medicine at the University of resistant properties then become a major Pennsylvania, used a $10m grant problem as the body is unable to reject the from the National Institute for Environmental material. This causes inflammation at the site takes aim at asbestos THealth Sciences (NIEHS) to set up the Penn and can ultimately lead to the development Superfund Research and Training Program of a cancer known as mesothelioma. Those (SRP) Center: a collaborative reactor for who worked with the material are most at scientists working on superfund research. It risk, but family members and communities exposure brings together all the elements necessary near mines and industrial processing centres to support world-leading science and has six are also affected. Its persistence in the specific project areas under investigation. environment and potential for disturbance Each of the projects addresses a specific through human activity are also major community concern. factors in its toxic legacy.
Superfund sites exist across the United PAINSTAKING DETECTIVE WORK States (US), where federal funds are In communities where exposure levels committed to aid the clean-up of sites are difficult to assess with any accuracy, a contaminated by hazardous materials or method of calculating individual risk is a vital pollutants. One such site, the BoRit Asbestos tool to direct clinical monitoring and follow- site in Ambler, Pennsylvania, is a cause up studies. Dr Blair is investigating how of concern to local communities who are approaches used to identify biomarkers in worried about asbestos contamination other disease states, such as his pioneering from lingering industrial waste. A town work on Friedreich’s ataxia, can be turned built almost entirely on its asbestos mining to asbestos exposure. Oxidative stress industry, Ambler suffers the legacy of this (the response of cells to increased levels of once promising mineral which became the reactive oxygen species) is a prime target pariah of twentieth-century industry. and thought to be associated with asbestos exposure. This can be effectively measured A FELONIOUS FIBRE in blood samples by analysing metabolites Asbestos is a silicate mineral known for in the serum (the fraction of blood left its naturally fibrous nature. It was mined extensively in the early twentieth century and used in building materials, as well as many other applications, because of its desirable mechanical properties. Light, strong and resistant to heat, it was often mixed with concrete and other binders to create panels or fittings with these attributes. Each visible fibre, however, is
A town built almost entirely on its asbestos mining industry, Ambler suffers the legacy of this once promising mineral which became the pariah of twentieth-century industry
47 Cancer
Figure 1 Penn SRP Center pro ects addressing the six Detail
ma or concerns of the Ambler Community RESEARCH OBJECTIVES Dr Blair’s research at the Penn SRP Center Why was the Penn SRP Center formed? as biomarkers for the early detection of aims to identify biomarkers of asbestos Phytoremediation: Can asbestos be remediated The National Institute of Environmental mesothelioma. The Amber community is exposure. Knowing which biomarkers Health Science funded the Center of participating in these biomarker studies. signal previous asbestos exposure will Pro ect 1 in situ Excellence in Environmental Toxicology help practitioners establish whether (CEET), directed by Dr Trevor Penning, in Why are these biomarkers present in an individual is at risk of developing 2008. The Community Engagement and asbestos exposure? asbestos-related diseases. Environmental Science: Is asbestos transported Outreach Director of the CEET, Dr Edward Asbestos is a fiber and so exposure cannot Pro ect 2 through soil and water Emmett, then began participating in the be analysed directly in the systemic FUNDING community advisory group in Ambler, PA circulation like a regular chemical. Instead, National Institute for Environmental where there is a Superfund Asbestos site serum biomarkers of response to asbestos Health Sciences (NIEHS) P42ES023720 Epidemiology: Why is there a cluster of mesothelioma known as the BoRit site. The concerns of the exposure have to be discovered. Asbestos Amber community were too extensive for is known to cause oxidative stress and COLLABORATORS Pro ect 3 among women in Ambler the CEET to deal with and so Dr Penning the challenge is to discover biomarkers From Penn SRP Center: Brenda Casper, invited Dr Blair to form the Penn SRP Center that differentiate asbestos-induced PhD; Reto Gieré, PhD; Douglas Jerolmack, in order to address these concerns. The six oxidative stress from other causes of PhD; Fran Barg, PhD; Edward Emmett, Drs Blair and Emmett with community leaders Is there a genetic predisposition to (Diane Morgan, Bob Adams and Sharon Vargas) at Cancer Genetics: projects in the Center came directly from oxidative stress such as cigarette smoking. PhD; Joseph Testa, PhD; Rebecca A the BoRit Asbestos Superfund Site in Ambler, PA Pro ect 4 asbestos-induced mesothelioma questions posed by the community (see Asbestos exposure is the major cause of Simmons, MD; Melpo Christofidou- Figure 1). mesothelioma and so biomarkers for the Solomidou, PhD; Steven M Albelda, MD; after it has clotted and the cells have been early detection of mesothelioma will also Clementina Mesaros, PhD; Richard Pepino; removed). Chemoprevention: Can asbestos-induced mesothelioma What are the advantages to this model be useful in identifying a prior exposure to Wei-Ting Hwang; Trevor M Penning, PhD. be prevented of research establishment? asbestos. Other key collaborators: David R Lynch, Using advanced chromatography techniques Pro ect 5 Research involves bi-directional knowledge MD, PhD; Garret A FitzGerald, MD, FRS; and mass spectrometry to separate out the exchange in order that the Penn SRP What do you hope the centre will Kathryn E Wellen; Nathaniel W Snyder, constituents of the samples, the researchers Center can address the Ambler community achieve for the local community? PhD. are able to create a series of chromatograms Diagnostics: Is there a blood test for asbestos concerns. This differs from the traditional The Penn SRP Center provides an from healthy serum and compare it to that Pro ect 6 exposure and mesothelioma model in which researchers simply assume independent body for the community BIO of the disease state. This technique has that the community will benefit from members to express concerns that Dr Blair received his PhD provided a list of biomarkers which show lack their research. Community engagement they feel have not been addressed in Organic Chemistry in of normal regulation in asbestos-exposed connects the Penn SRP Center’s science satisfactorily by government 1971 from Imperial College individuals, potentially providing a template with issues that are locally relevant and agencies. It also provides a resource of Science and Technology, against which unconfirmed cases can be The major benefit of the SRP Center is complements the research strengths and for medical intervention if a particular London, under the mentorship of assessed. problem-solving goals of the Center. community member is concerned about Nobel Laureate Sir Derek H R Barton. that researchers working on separate their risk for mesothelioma. Once a He was appointed as the A.N. Richards CALL FOR BACKUP aspects of asbestos remediation, toxicity, How will your research help identify at- serum biomarker of response to asbestos Professor of Systems Pharmacology and This is just one of the projects at the SRP risk individuals? exposure has been validated, it will provide Translational Therapeutics at the University which houses six distinct research teams and exposure can collaborate effectively Biomarker studies conducted in Project 6 a reliable way for concerned individuals to of Pennsylvania in 1997 and Vice-Chair working on different aspects of asbestos of the Center will identify serum biomarkers find out whether or not they been exposed of the Department in 2002. He became toxicity: of response to asbestos exposure as well to asbestos. Director of the Penn SRP Center in 2014. • Project 1, led by Dr Brenda Casper, • Project 5, led by Associate Professor Melpo uses the same oxidative stress markers Dr Blair has published over 370 refereed researching how plants and fungi can be Christofidou-Solomidou and Professor identified by the team to investigate the manuscripts and he has an h-index of 63. utilised in the remediation of asbestos Steven Albelda, looking into therapeutic efficacy of flaxseed lignans as potential contamination in the environment. agents for the prevention of mesothelioma chemotherapeutic agents. Reto Gieré), which gives physicians valuable previously exposed individuals are common CONTACT • Project 2, led by Professors Douglas in asbestos-exposed individuals. insight into the causes and treatment of around the world, and in some areas, Ian A Blair, PhD Jerolmack and Reto Gieré, investigating • Project 6, led by Professor Ian Blair and The Center also brings together data- asbestos-related diseases. asbestos extraction and use continues Systems Pharmacology & Translational the mobility and fate of asbestos in the Assistant Professor Anil Vachani, studying crunching expertise in the form of the despite the known hazards. Therapeutics environment to prevent offsite migration. biomarkers of asbestos exposure. Biostatistics Research Support Core (led by SERVING THE WIDER COMMUNITY University of Pennsylvania • Project 3, led by Associate Professors Dr Wei-Ting Hwang), provides administrative This model has shown how research centres, The Penn SRP Center shows how it is possible 853 BRB II/III Frances Barg and Douglas Wiebe, studying This means that Dr Blair’s team are not functions to free up researchers' time and, engaging with local communities, can to produce a truly collaborative research and 421 Curie Boulevard epidemiological and ethnographic data on operating alone; the major benefit of the perhaps the key component, provides a facilitate interdisciplinary collaboration to teaching environment, making it possible to Philadelphia, PA 19104-6160 the incidence of asbestos-related diseases SRP Center is that researchers working mechanism for the findings to quickly benefit build creative solutions to local problems combine effective bi-directional community in the community. on separate aspects of asbestos toxicity the local community through the Research with global significance. The problem of engagement with innovative scientific E: [email protected] • Project 4, led by Dr Joseph Testa and Prof can collaborate effectively and share their Translation Core (headed up by Mr Richard asbestos-related diseases, while particularly research. This in turn produces translational T: +1 215 573 9880 Rebecca Simmons, investigating animal findings. For example, Project 6 is providing Pepino) and Community Engagement Core close to the hearts of the communities science that can rapidly benefit local W: http://www.med.upenn.edu/blairlab/ models of mesothelioma to understand data for Project 4 to use in assessing (led by Drs Edward Emmett and Fran Barg). around the BoRit site, has international communities as well as other populations Penn SRP Center: http://www.med.upenn. the genetics of mesothelioma and explore remediation strategies through animal There is also a vital training element to the relevance. Due to its ubiquity in twentieth- at risk for exposure and other scientists edu/asbestos/ possible remediation strategies. models of asbestos exposure, while Project 5 centre (led by Drs Trevor M Penning and century construction, populations of working in the field.
48 www.researchfeatures.com www.researchfeatures.com 49