John Goudreau, Ph.D., D.O.
- Drug Discovery and Receptor Faculty, Neuropharmacology Faculty
Pharmacology & Toxicology
Assoc. Prof.; Director, Neuro-Degenerative Research Unit
B436 Life Sciences
1355 Bogue Street
East Lansing, MI 48824
Fields of Interest: My research interests are focused on genetic and environmental factors involved in the pathogenesis of neuro-degenerative disorders such as Parkinson's Disease (PD).
- 1988 - B.S. and B.A., Michigan State University
- 1994 - Ph.D., Pharmacology and Toxicology, Michigan State University
- 1995 - D.O., College of Osteopathic Medicine, Michigan State University
- 2000 - Residency, Department of Neurology, May Clinic/Rochester
- 2001 - Movement Disorders Fellowship, Mayo Clinic/Rochester
- 2001-2007 - Assistant Professor, Neurology & Ophthalmology, and Pharmacology & Toxicology, Michigan State University
- 2007-present - Associate Professor, Neurology & Ophthalmology, and Pharmacology & Toxicology, and Neuroscience Program, Michigan State University
Biography & Current Research
My research interests are focused on genetic and environmental factors involved in the pathogenesis of neuro-degenerative 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 environmental 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 neuro-degenerative disease.
- "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. We currently focused on the role of parkin in the unique ability of hypothalamic dopaminergic neurons to recover from a neuronal injury.
- "Environmental neurotoxicant exposure-induced nuclear-mitochondrial cascade mechanisms of neuro-inflammation and neurodegeneration in Parkinson’s disease.” Neurotoxicant exposure in vivo and in vitro will be used to assess the role of the peripheral benzodiazepine receptor (also known as 18 KDa translocator protein or TSPO) as a pivotal, neuroinflammation-dependent, step mediating the cycle of neuroinflammation and dopaminergic cell death.
- “Michigan State University Parkinson Disease Clinical Center.” This project is part of the NINDS Exploratory Trials in PD consortium and seeks to test novel agents for neuroprotective therapy in patients with early Parkinson’s disease. We are currently investigating the disease modifying effects of creatine in subjects with mild, treated Parkinson’s disease.
- “Phase IV Trial of the disease modifying effect of rasagiline, a novel MAO-B inhibitor, in patients with Parkinson disease subjects who participated in the ADAGIO study.” The goal of this project is to deter-mine if disease modifying effects of rasagiline observed in the ADAGIO study are persistent over time.
Awards & Achievements
National and State Positions
- Vice-Coordinator, COMLEX Level 1CE, National Board of Osteopathic Medical Examiners
- National Institutes for Neurological Disorders and Stroke, NSD-B (Ad Hoc 2007-present) Study Section, NIEHS, Special Emphasis Panel: Centers for Neurodegeneration Science
- Member, Parkinson Study Group
- Member, Professional Advisory Board, Michigan Parkinson Foundation
Committees & Activities
- Research and Graduate Studies Committee, College of Osteopathic Medicine
- Executive Committee, Department of Neurology, Michigan State University
Full list of publications at MSU Scholars
- The Parkinson Study Group SURE-PD Investigators, Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, IsaacsonSH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K. Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2013 Dec 23. doi: 10.1001/jamaneurol.2013.5528. [Epub ahead of print] PubMed PMID: 24366103.
- Parkinson Study Group. Phase II safety, tolerability, and dose selection study of isradipine as a potential disease-modifying intervention in early Parkinson's disease (STEADY-PD). Mov Disord. 2013 Nov;28(13):1823-31. doi: 10.1002/mds.25639. Epub 2013 Sep 30. PubMed PMID: 24123224.
- Benskey M, Lee KY, Parikh K, Lookingland KJ, Goudreau JL. Sustained resistance to acute MPTP toxicity by hypothalamic dopamine neurons following chronic neurotoxicant exposure is associated with sustained up-regulation of parkin protein. Neurotoxicology. 2013 Jul;37:144-53. doi: 10.1016/j.neuro.2013.04.002. Epub 2013 May 1. PubMed PMID: 23643664.
- Tiernan CT, Edwin EA, Goudreau JL, Atchison WD, Lookingland KJ. The role of de novo catecholamine synthesis in mediating methylmercury-induced vesicular dopamine release from rat pheochromocytoma (PC12) cells. Toxicol Sci. 2013 May;133(1):125-32. doi: 10.1093/toxsci/kft025. Epub 2013 Feb 19. PubMed PMID: 23425605; PubMed Central PMCID: PMC3627552.
- Hsu SC, Sears RL, Lemos RR, Quintáns B, Huang A, Spiteri E, Nevarez L, Mamah C, Zatz M, Pierce KD, Fullerton JM, Adair JC, Berner JE, Bower M, Brodaty H, Carmona O, Dobrici? V, Fogel BL, García-Estevez D, Goldman J, Goudreau JL, Hopfer S, Jankovi? M, Jaumà S, Jen JC, Kirdlarp S, Klepper J, Kosti? V, Lang AE, Linglart A, Maisenbacher MK, Manyam BV, Mazzoni P, Miedzybrodzka Z, Mitarnun W, Mitchell PB, Mueller J, Novakovi? I, Paucar M, Paulson H, Simpson SA, Svenningsson P, Tuite P, Vitek J, Wetchaphanphesat S, Williams C, Yang M, Schofield PR, de Oliveira JR, Sobrido MJ, Geschwind DH, Coppola G. Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification. Neurogenetics. 2013 Feb;14(1):11-22. doi: 10.1007/s10048-012-0349-2. Epub 2013 Jan 20. PubMed PMID: 23334463.