This renewal of K24ES017765 builds on substantial scientific and mentoring progress made in the last five years. Scientifically, the investigators have conducted impactful human clinical epidemiological, imaging, and pathology studies investigating the neurotoxic effects of manganese (Mn) exposure. Manganese (Mn) is a metal with complex pharmacology due to its role as both an essential trace element and an established neurotoxicant. The scientific aims of this renewal provide a critical link between Mn deposition in tissue and biomarkers in Mn- exposed workers, consistent with the theme of this application. A better understanding of these relationships and the biology of the MRI signal intensity in humans will provide essential information to inform future studies on the health effects of Mn. The investigators propose to leverage a long-standing relationship with our colleagues in South Africa to collect neuropathologic (brain) and other tissue from deceased Mn miners to investigate the inter- relationship between Mn exposure, state-of-the-art quantitative MRI metal sequences, and tissue Mn/Fe concentrations. This study will inform their currently funded research in Mn-exposed welders and future studies in South African Mn miners. In addition, it will provide a rare opportunity to investigate metal deposition in brain and other tissues in Mn-exposed subjects in order to develop and validate biomarkers for Mn exposure. Over the last five years, the candidate has mentored numerous trainees in his neurodegenerative environmental epidemiology laboratory as well as trainees studying migraine, autism, stroke, musculoskeletal disorders, and physical therapy/rehabilitation. The protected mentoring time afforded by the K24 has resulted in three KL2 and three K23 grants awarded to my trainees, numerous foundation training grants, and over 30 publications. The activities outlined in the mentoring plan are the logical next step in the evolution of his mentoring career and will have two key components. First, the candidate will take on a more prominent mentoring role in the Washington University KL2 program, including developing a grant writing program based upon a peer-mentoring approach. Second, he will serve as an international mentor at the University of the Witwatersrand, where he will assist in mentoring public health students and teach a course on NIH grant writing.
This K24 mentoring grant has two components, a mentoring plan and new research. The mentoring will include serving as a program mentor for the Washington University KL2 program, serving as a graduate student mentor at the University of the Witwatersrand in Johannesburg, South Africa, and teaching NIH style grant courses at both institutions. The new research will investigate brain and non-brain tissue manganese and iron deposition in South African manganese and non-manganese miners in relation to occupational exposures.
|Racette, Brad A; Gross, Anat; Criswell, Susan R et al. (2018) A screening tool to detect clinical manganese neurotoxicity. Neurotoxicology 64:12-18|
|Racette, Brad A; Gross, Anat; Vouri, Scott Martin et al. (2018) Immunosuppressants and risk of Parkinson disease. Ann Clin Transl Neurol 5:870-875|
|Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2018) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology 64:43-49|
|Camacho-Soto, Alejandra; Gross, Anat; Searles Nielsen, Susan et al. (2018) Inflammatory bowel disease and risk of Parkinson's disease in Medicare beneficiaries. Parkinsonism Relat Disord 50:23-28|
|Searles Nielsen, Susan; Hu, Shu-Ching; Checkoway, Harvey et al. (2017) Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington State. J Agromedicine 22:215-221|
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|Camacho-Soto, Alejandra; Warden, Mark N; Searles Nielsen, Susan et al. (2017) Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data. Ann Neurol 82:744-754|
|Racette, Brad A; Searles Nielsen, Susan; Criswell, Susan R et al. (2017) Dose-dependent progression of parkinsonism in manganese-exposed welders. Neurology 88:344-351|
|Martin, W R W; Hartlein, J; Racette, B A et al. (2017) Pathologic correlates of supranuclear gaze palsy with parkinsonism. Parkinsonism Relat Disord 38:68-71|
|Searles Nielsen, Susan; Checkoway, Harvey; Criswell, Susan R et al. (2015) Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders. Parkinsonism Relat Disord 21:355-60|
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