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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24ES017765-08
Application #
9122428
Study Section
Special Emphasis Panel (ZES1-LKB-J (K3)1)
Program Officer
Hollander, Jonathan
Project Start
2009-05-01
Project End
2019-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
8
Fiscal Year
2016
Total Cost
$167,220
Indirect Cost
$12,387
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara et al. (2017) Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2017) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology :
Racette, Brad A; Gross, Anat; Criswell, Susan R et al. (2017) A screening tool to detect clinical manganese neurotoxicity. Neurotoxicology :
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
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
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
Criswell, Susan R; Nelson, Gill; Gonzalez-Cuyar, Luis F et al. (2015) Ex vivo magnetic resonance imaging in South African manganese mine workers. Neurotoxicology 49:8-14
Morris, Marie; Willis, Allison W; Searles Nielsen, Susan et al. (2015) Physician response to a medication alert system in inpatients with levodopa-treated diseases. Neurology 85:420-4
Andruska, Kristin M; Racette, And Brad A (2015) Neuromythology of Manganism. Curr Epidemiol Rep 2:143-148
Safarpour, Delaram; Thibault, Dylan P; DeSanto, Cori L et al. (2015) Nursing home and end-of-life care in Parkinson disease. Neurology 85:413-9

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