Contact Info:Email: john.goudreau@ht.msu.edu Phone: (517) 432-2478 Fax: (517) 353-8915

Research Synopsis

My research interests are focused on genetic and environmental factors involved in the pathogenesis of neurodegenerative disorders such as Parkinson's Disease (PD). PD is a progressive illness characterized by resting tremor, slowness and stiffness of movement in addition to problems with balance and walking. PD is a common disease, affecting nearly 1 million people in the United States. The cause of PD is unknown, but combinations of both genetic and environmental factors are thought to play an important role. The goal of our research is to develop novel neuroprotective or neurorestorative therapeutics to slow, halt or reverse the progressive neurodegeneration for patients with Parkinson's disease.

The work in my laboratory extends from the bench to the bedside. We use rodent and cell culture models to identify and characterize genetic and environmental factors that may lead to PD. Selective neurotoxin exposure, alone or in combination with transgenic or knockout animals are used to test the importance of environmental and genetic factors. Animals will be evaluated on the basis of their motor behavior in combination with neurochemical, pathological, and immunohistochemical changes in selected regions of the brain. In addition, genome-wide mRNA expression profiling is used to identify anticipated or novel changes in gene expression in animals or regions of brain with differential sensitivity to enviornmental neurotoxins. Using these approaches, novel target for neuroprotective therapies in PD will be identified and validated. We also use animal models to screen potential neuroprotective compound for efficacy and safety. Finally, we conduct clinical trials testing neuroprotective therapies in patients with Parkinson's disease and are working to develop neuroimaging biomarkers of neurodegenerative disease.

Current Projects

"Neuroprotective role of a-synuclein using in vivo and in vitro models of Parkinson's Disease." The goal of this project is to understand the molecular mechanisms whereby a-synuclein modifies nigrostriatal DA neurodegeneration in response to neurotoxin exposure using in vivo and in vitro models of Parkinson's disease.

"Molecular mechanisms of selective neurotoxin vulnerability in nigrostriatal versus hypothalamic dopaminergic neurons." The goal of this project is to understand the molecular mechanisms that render nigrostriatal DA neurons sensitive and hypothalamic DA neurons resistant to exogenous neurotoxins

"Neuroprotective effects of a novel NADPH-oxidase inhibitor in an animal model of Parkinson's disease." The goal of this project is to provide pre-clinical efficacy and safety data for the use of a potential neuroprotective agent in the chronic MPTP mouse model of Parkinson disease.

"Michigan State University Parkinson Disease Clinical Center" This project seeks to test novel agents for neuroprotective therapy in patients with early Parkinson’s disease.

"Phase IIIb Trial of a novel MAO-B inhibitor as a Neuroprotective Therapy in Parkinson’s Disease." The goal of this project is to determine if the MAO-B inhibitor, rasagiline, has neuroprotective efficacy in a cohort of patients with early Parkinsons’s Disease.

"Environmental neurotoxin exposure-induced nuclear-mitochondrial cascade mechanisms of neurodegeneration in Parkinson’s disease.” Prototype agents, representing potential exposure risks to military personnel, will be used to assess the role of peripheral benzodiazepine receptors as a pivotal, neuroinflammation-dependent, step mediating the apoptosis inducing factor/poly ADP ribose polymerase pathway of dopaminergic cell death.

Research Support: National Insitutes for Neurological Disorders and Stroke (NS053380-01; NS049057-01A1; NS051406-01), US Army Research Acquisition Activity (Neurotoxin Exposure Treatment Research Program, ERMS 06144019), Pfizer, Teva Pharmaceutical Industries.

National & State Positions
Chair COMLEX Level 1 Committee, National Board of Osteopathic Medical Examiners.

National Insitutes for Neurological Disorders and Stroke, Special Emphasis Review Panel: Cell Biological Studies of Parkinson's Disease

Michael J. Fox Foundation, Animal Models of Parkinson’s disease and Therapy Development Initiative Review Panels

Parkinson Study Group Member

Professional Advisory Board, Michigan Parkinson Foundation

University Committees

Research and Graduate Studies Committee, College of Osteopathic Medicine

Executive Committee, Department of Neurology, Michigan State University

Selected Publications

Duka, T., Rusnak, M., Drolet, R.E., Duka, V., Wersinger, C., Goudreau, J.L., Sidu, A., Alpha-synuclein induces the hyperphosphorylation of tau in the MPTP model of parkinsonism. FASEB Journal, 20:2302-2312, 2006.

Drolet, R.E., Behrouz, B., Lookingland, K.J., Goudreau, J.L., Substrate-Mediated Enhancement of Phosphorylated Tyrosine Hydroxylase in Nigrostriatal Dopamine Neurons: Evidence for aRole of a-Synuclein, J Neurochem, 96:950-959, 2006.

Zheng, J.S., Tang, L.L., Zheng, S.S, Zhan, R.Y , Zhou, Y.Q., Goudreau, J., Kaufman, K., Chen, A.F., Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson’s disease. Molecular Brain Research, 134:155-161, 2005.

Drolet, R.E., Behrouz, B., Lookingland, K.J. Goudreau, J.L., “Mice Lacking -Synuclein Have An Attenuated Loss Of Striatal Dopamine Following Prolonged Chronic MPTP Administration. Neurotoxicology, 25:761-769, 2004

Goudreau, J.L., Maraganore, D.M., Farrer, M.J., Lesnick, T.G., Singleton, A.B., Hardy, J.A., Rocca, W.A., Case-control study of dopamine transporter-1, monoamine oxidase-B and catechol-O-methyl transferase polymorphisms in Parkinson’s disease. Movement Disorders, 17:1305-1311, 2002.

Goudreau, J.L., Wijdicks, E.F.M., Emery, S.F. Complications and predisposing factors during apnea testing in the determination of brain death. Neurology, 55:1045-1048, 2000.

Lincoln, S., Gwinn-Hardy, K., Goudreau, J., Chartier-Harlin, M.C., Lynch, T., Hardy, J., Farrer, M. No pathogenic mutations in the persyn gene in Parkinson’s disease. Neurosci Lett, 259:65-66, 1999.

Book Chapters

Goudreau, J.L., Medical management of advanced Parkinson’s disease, Clinics in Geriatric Medicine, 22:753-772, 2006.

Goudreau, J.L. Hereditary Spinocerebellar Degeneration, in Neurological Therapeutics: Principles and Practice, 2nd Edition, John Noseworthy, ed. Martin Dunitz, London, Chapter 214, 2496-2509, 2006.

Goudreau, J.L., Ahlskog, J.E., Symptomatic Treatment of Parkinson’s Disease: Levodopa, in Parkinson’s Disease, Ebadi, M and Pfeiffer, R. eds., CRC Press, New York, Chapter 56, 713-728, 2005