The objective of this predoctoral and postdoctoral training program is to educate a new generation of environmental pathologists to use the tools of cell biology, molecular biology, and biochemistry to study basic mechanisms of disease related to environmental exposures. The central focus is an independent laboratory research project to explore the pathogenesis of altered reproductive function, adverse developmental and pregnancy outcomes, neurodegenerative disease, or cancer resulting from exposure to industrial wastes and environmental contaminants including metals, plasticizers, pesticide, particulates and fibers. Predoctoral trainees will be recruited with majors in biology, chemistry, toxicology, or environmental sciences and a commitment to basic research on mechanism of disease and environmental health. Postdoctoral trainees may hold a doctoral degree in a basic science discipline, pathology, or toxicology. All predoctoral trainees are required to learn the basic mechanisms and morphologic manifestations of human disease. Training is also required to learn the basic mechanisms and morphologic manifestations of human disease. Training is also provided in molecular pathology, imaging, and environmental toxicology, signal transduction, carcinogenesis, and molecular genetics. All trainees will be instructed in the responsible conduct of research and will have the opportunity to develop their communication and teaching skills at the Sheridan Center for Teaching and Learning at Brown University. Didactic courses are supplemented by weekly research seminars, student journal clubs, career development workshops, and an annual Environmental Pathology Symposium, Strong emphasis is placed on communication skills, grantsmanship, interdisciplinary approaches, and implications of basic research for recognition and prevention of human disease. Opportunities are provided for clinical and translational research collaborations at Rhode Island Hospital and Women &Infants'Hospital, as well as field work and community outreach at existing industrial waste sites and Brownfields in Rhode Island. The eight faculty have active, well-funded research programs ($4.4 million in annual direct costs) and access to modern research facilities equipped for quantitative imaging, laser capture microdissection, genomics and proteomics, flow cytometry, transgenic animals, and access to human tissue and specimen banks. These trainees will be prepared to apply their basic research expertise to the definition, analysis, and solution of complex environmental health problems working together with experts in epidemiology, toxicology, public health, and government and regulatory agencies. BACKGROUND This Training in Environmental Pathology program is in its 14th year of support and is centered in the department of Pathology and Laboratory Medicine in the Division of Biology and Medicine at Brown University. The program enlists eight faculty, five of which are physicians, as mentors that have environmental related research in the areas of pulmonary, hepatic, reproductive and neurological health. The research focuses on mechanistic, translational and public health outcomes from environmental agents and common cofactors. Dr. Agnes Kane MD/PhD has acted as Director of the program since its inception and the Co-Director is Dr. Kim Boekelheide MD/PhD. The application requests funding for five predoctoral and two postdoctoral positions. Recruitment of a new Dean in 2005 with a strong mandate to improve graduate education in the Division of Biology and Medicine was considered an advantageous asset to the Environmental Pathology Training Program. In 2006 the Training Program recruited its largest applicant pool. It was noteworthy that the program has over $4 million in direct cost funding. A major change in the predoctoral curriculum was a reduction in the number of required courses and seminars and transfer of the first research rotation to the first semester. This change was considered to facilitate the trainee's selection of a thesis research mentor at the end of the second semester and to facilitate the trainee's progression to completion of the preliminary examination at the end of the second year. The program has multiple interactive activities with trainees to address the responsible conduct of research. In response to feedback received via internal and external reviews the number of invited speakers representing diverse career pathways has been increased. This application seeks continuing support (years 16-20) for training in the environmental pathology track within the Pathobiology Graduate Program at Brown University. This program is part of the Division of Biology and Medicine and Center for Environmental Studies. Eight preceptors are named in the renewal application, down from ten named in 2001.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Institutional National Research Service Award (T32)
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Special Emphasis Panel (ZES1-LWJ-C (AK))
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Shreffler, Carol K
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Brown University
Schools of Medicine
United States
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Leggett, Susan E; Khoo, Amanda S; Wong, Ian Y (2017) Multicellular tumor invasion and plasticity in biomimetic materials. Biomater Sci 5:1460-1479
Valentin, Thomas M; Leggett, Susan E; Chen, Po-Yen et al. (2017) Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics. Lab Chip 17:3474-3488
Leggett, Susan E; Wong, Ian Y (2017) Nanomedicine: Catching tumour cells in the zone. Nat Nanotechnol 12:191-193
Rodd, April L; Messier, Norma J; Vaslet, Charles A et al. (2017) A 3D fish liver model for aquatic toxicology: Morphological changes and Cyp1a induction in PLHC-1 microtissues after repeated benzo(a)pyrene exposures. Aquat Toxicol 186:134-144
Dai, M S; Hall, S J; Vantangoli Policelli, M M et al. (2017) Spontaneous testicular atrophy occurs despite normal spermatogonial proliferation in a Tp53 knockout rat. Andrology 5:1141-1152
Gamboa Castro, Marielena; Leggett, Susan E; Wong, Ian Y (2016) Clustering and jamming in epithelial-mesenchymal co-cultures. Soft Matter 12:8327-8337
Borgas, Diana; Chambers, Eboni; Newton, Julie et al. (2016) Cigarette Smoke Disrupted Lung Endothelial Barrier Integrity and Increased Susceptibility to Acute Lung Injury via Histone Deacetylase 6. Am J Respir Cell Mol Biol 54:683-96
Francois-Vaughan, Heather; Adebayo, Adeola O; Brilliant, Kate E et al. (2016) Persistent effect of mTOR inhibition on preneoplastic foci progression and gene expression in a rat model of hepatocellular carcinoma. Carcinogenesis 37:408-419
Vantangoli, Marguerite M; Wilson, Shelby; Madnick, Samantha J et al. (2016) Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues. Toxicol Lett 248:1-8
Leggett, Susan E; Sim, Jea Yun; Rubins, Jonathan E et al. (2016) Morphological single cell profiling of the epithelial-mesenchymal transition. Integr Biol (Camb) 8:1133-1144

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