Michael D. McClean - US grants

DESCRIPTION (provided by applicant) The investigators are applying to continue a successful interdisciplinary pre-doctoral training program focused on Environmental Epidemiology in Community Settings (EECS program) within the Department of Environmental Health at the Boston University School of Public Health (BUSPH). The EECS program consists of a specific training regimen that is located within a mature doctoral program and designed to prepare pre-doctoral students to use the most sophisticated methods currently available to advance the state of knowledge and develop new methods in community-oriented environmental epidemiology. The program has an intellectual commitment to interdisciplinary work, built on a robust collaborative research program within BUSPH and with outside research partners and designed to provide research training that is interdisciplinary in spirit, substance and outcome. The investigators will recruit two pre-doctora trainees each year for a steady state census of six trainees and build on a demonstrated record of recruiting trainees from underrepresented groups. EECS trainees typically receive support from the training grant during their first three years and then transition to external research grants awarded either to the trainee (e.g. NIH F-series awards, EPA STAR fellowships) or to faculty mentors (e.g. NIH R01 awards, EPA STAR grants). An advisor is assigned upon entering the program to assist with selecting courses, identifying research rotations, and developing dissertation plans. The investigators offer a core curriculum that provides multidisciplinary training in environmental health, epidemiology, toxicology, biostatistics, and physiology. Clusters of advanced specialty courses are tailored to particular areas of ongoing research such as epidemiologic methods, social epidemiology, and exposure assessment. Trainees engage in three research rotations on active projects during their first year (fall, sprin, summer), which facilitates integration into the program and refinement of research interests. Additionally, the program provides regular opportunities for oral presentation, teaching, and proposal writing. Trainees are required to prepare a dissertation proposal by the end of their fift semester before scheduling their written and oral qualifying exams. Upon passing their exams, trainees establish a dissertation committee and engage in full-time research activities. Key enrichment activities of the training program include a weekly departmental research seminar, a biweekly proseminar and journal club, an annual research retreat, and explicit instruction in the responsible conduct of research. The Training Program Steering Committee (TPSC) reviews the progress of each trainee with respect to program milestones via course grades and progress reports submitted by the trainee and faculty mentor. The progress of the EECS program is evaluated via feedback from trainees at the end of each semester, reviews conducted by the External Advisory Committee, critical examination of successes and failures by the TPSC, and monitoring of graduates to track career paths and publications.

This application proposes that the BU SRP Training Core will continue to provide interdisciplinary training in laboratory science, bioinformatics and computational biology, while also expanding the Training Core to act as a common reference point for all graduate students and post-doctoral fellows who work within the BU SRP program (including those who are supported by other BU SRP projects, other related training programs, and directly by the Training Core). The Training Core will directly support two students a year in bioinformatics techniques applied to the laboratory sciences, with an emphasis on analysis of high throughput, genome-wide data sets and on molecular modeling. This focus responds to the strategic importance of these methods for the biology of the future, the relative lack of exposure to them in traditional laboratory training programs, and the unique resources ofthe applicant institution. A major element ofthe program theme, the susceptibility ofthe developing organism to low-level xenobiotic exposures through a variety of pathways, is ideally suited to be the context for this cross discipline training. After nomination by project PIs at the end of their first year of study, two students will be selected by a Steering Committee consisting ofthe Program Director, the Training Core Director, and two additional BUSRP PIs, contingent on their commitment to one of the laboratories within the BUSRP. These students will receive appropriate core courses covering bioinformatics, reproduction and development, environmental health, and toxicology during their training program. In addition, we focus on communication skills, not only within the scientific community but to disseminate scientific knowledge to the broader community and to close the communication gap between bench and laboratory science and the public at large. Importantly, the Training Core will orient graduate students and post-doctoral fellows supported by BU SRP projects or the Training Core to the mission, activities and needs of the NIEHS SRP, EPA and state environmental and health agencies; and thereby develop a sense of shared mission and peer network as they work towards advancing the science needed to provide a firm foundation for solving the complex health and environmental issues associated with the nation's hazardous waste sites.

DESCRIPTION (provided by applicant): The proposed application, entitled Precursors and Prognosis of Traumatic Brain Injury in Young to Middle Aged Adults seeks to determine whether single or repeated traumatic brain injuries (TBI) increase risk for later life decline in cognition mood, behavior and daily function. This project leverages already available health, lifestyle, biomarker, genetic, cognitive and neuroimaging data and combines it with proposed acquisition of new TBI data recommended as Common Data Elements (CDE) by the National Institute of Neurological Disorders and Stroke (NINDS). This study marks an initial effort to systematically collect specific NINDS CDE on TBI in a community-based sample. Further, while the concept of developing risk profile scores originated within the Framingham Heart Study and have been widely used, risk profile scores have not been utilized for documenting activities that can lead to impact exposures and TBIs in order to characterize whether those exposures lead to later life consequences. The proposed study will obtain detailed histories of military service, sports participation, and employment to retrospectively assess exposure to impacts, and will also determine prevalence of diagnosed TBI in the Framingham Heart Study Generation 3 (Gen 3; n=4095) and its smaller multi-ethnic Omni Generation 2 (n=410; Omni Gen 2) cohorts. We will then relate these risk factors to available and new computerized measures of cognition to determine whether history of impact exposures and/or diagnosed TBI is associated with cognitive impairment and accelerated decline. We will also examine whether history of impact exposures and/or diagnosed TBI is associated with smaller brain volumes and compromised white matter integrity, particularly in the regions of the brain linked to memory and executive function. Further we will address the question of whether these risk factors are associated with changes in mood, behavior and daily functioning. Finally, we will seek to identify metabolic and inflammatory biomarkers associated with history of impact exposures and/or diagnosed TBI and whether specific genetic markers modify the relationship between TBI and chronic health outcomes. Our focus on the potential long-term consequences of engaging in activities that can lead to impact exposures and TBIs in the general population has significant implications for public health.

Project Summary The proposed pilot study application, entitled Impact of Traumatic Brain Injury on Brain Aging and Dementia seeks to determine whether history of traumatic brain injury (TBI) increases risk for later life neurodegenerative decline in the Framingham Heart Study Generation 1 (Gen 1; n=5209) cohort. This project leverages available health, lifestyle, biomarker, genetic, cognitive and neuroimaging data to study TBI and its consequences in a comprehensively characterized community-based sample that has been followed prospectively for dementia for nearly 40 years. For this pilot project, we plan to identify moderate to severe TBI that is validated by medical records (vTBI) and document the prevalence of vTBI. We will then determine whether history of vTBI is associated with increased risk for accelerated cognitive decline and dementia, particularly Alzheimer's Disease. We will also examine whether the TBI metrics are associated with greater brain atrophy and changes in white matter. Further, we will address the question of whether history of vTBI is associated with short- and long-term changes in mood and daily functioning. Finally, we will also seek to identify metabolic and inflammatory biomarkers associated with vTBI and whether specific genetic markers modify the relationships between TBI and health outcomes. The results from this pilot study will lay the foundation for a larger scale study. The primary long-term objective is to determine whether the consequences of TBI are related to increased risk for dementia and other health related outcomes within a community-based sample. Results from this research will help determine the significant long- term public health implications of TBI.