Location and Contact Information
Parkinson’s disease (PD) is a multifaceted disorder that involves several neurotransmitter systems and a range of motor and non-motor behaviors. The most debilitating motor dysfunction is caused by a concomitant loss of dopamine-producing neurons in the substantia nigra pars compacta and dopamine in the striatum. Our lab focuses on how disruption of the proper storage and release of dopamine from vesicles plays a key role in the loss of dopamine neurons, leading to the development of disease. We use a combination of electrochemical and pharmacological techniques in a wide range of models. We study the role of vesicular monoamine transporter (VMAT2) and synaptic vesicle glycoprotein 2C (SV2C) in Parkinson’s disease pathogenesis.
The exposome concept highlights the importance of environmental factors in disease development. The exposomics approach allows for a systematic analysis of non-genetic contributors to neurodegenerative disease in an unbiased fashion. Using the untargeted metabolomics approach, a list of environmental chemicals was found to be enriched in human patients with Alzheimer’s Disease and Parkinson’s Disease, providing important targets for scientific analysis and policy consideration. The lab has also established a platform to study environmental determinants of aging in C. elegans using ultra high-resolution mass spectrometry-based metabolomics (UHRMS). This platform enables us to measure the impact of toxicants on longevity and age-related cognition in C. elegans. The same platform can be utilized to study human samples, making this method highly translational and providing insights into age-related diseases and potential medical intervention.
For additional information, please visit The Human Exposome Project https://humanexposomeproject.com/
About Dr. Miller
Dr. Miller moved to Columbia University in 2018. He is Professor of Environmental Health Sciences and Vice Dean for Research Strategy and Innovation at Mailman School of Public Health, Columbia University Irving Medical Center. He also has appointments in the Department of Molecular Pharmacology and Therapeutics and the Department of Neurology. As an international expert on the exposome, Dr. Miller is a faculty member of the Irving Institute CTSA, and is currently leading the Columbia Exposome Initiative. Dr. Miller began his work on the exposome in 2010. Since that time he has founded and directed the first NIH center on the exposome (HERCULES Exposome Research Center), authored the first book on the topic, and served as an advisor to several international groups. From 2013 to 2019, Dr. Miller served as the Editor-in-Chief of Toxicological Sciences, the flagship journal of the Society of Toxicology.
Dr. Miller completed his PhD in Pharmacology and Toxicology from the University of Georgia and postdoctoral training in molecular neuroscience at Emory University and Duke University. From 1998 to 2002, he was faculty member in the Division of Pharmacology and Toxicology at the University of Texas at Austin. Dr. Miller moved to Emory University in 2002. He served as Professor at the Department of Environmental Health in the Rollins School of Public Health and the Departments of Pharmacology and Neurology in the School of Medicine and Associate Dean for Research at Rollins School of Public Health from 2009 to 2018.
Vrinda’s expertise is metabolomics, bioinformatics and statistical analysis.
Inamdar AA, Hossain MM, Bernstein AI, Miller GW, Richardson JR, Bennett JW. Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19561-6. doi: 10.1073/pnas.1318830110. Epub 2013 Nov 11. PMC3845153.
Kelly M Lohr*,, Alison I Bernstein*,, Kristen A Stout, Amy R Dunn, Carlos R Lazo, Shawn P Alter, Minzheng Wang, Yingjie Li, Xueliang Fan, Ellen J Hess, Hong Yi, Laura M Vecchio, David S Goldstein, Thomas S Guillot, Ali Salahpour, Gary W Miller. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo. Proceedings of the National Academy of Sciences, USA. 2014 Jul 8;111(27):9977-82. PMC4103325. Highlighted in This Week in PNAS.
Lohr KM*, Stout KA, Dunn AR, Wang M, Salahpour A, Guillot TS, Miller GW. Increased Vesicular Monoamine Transporter 2 (VMAT2; Slc18a2) Protects against Methamphetamine Toxicity. ACS Chem Neurosci. 2015 May 20;6(5):790-9. PMC4489556.
Richardson JR*, Taylor MM, Shalat SL, Guillot TS 3rd, Caudle WM, Hossain MM, Mathews TA, Jones SR, Cory-Slechta DA, Miller GW. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J. 2015 May;29(5):1960-72. PMC4415012.
Lohr KM*, Chen M, Hoffman CA, McDaniel MJ, Stout KA, Dunn AR, Wang M, Bernstein AI, Miller GW. Vesicular Monoamine Transporter 2 (VMAT2) Level Regulates MPTP Vulnerability and Clearance of Excess Dopamine in Mouse Striatal Terminals. Toxicol Sci. 2016 Sep;153(1):79-88. PMID:27287315.
Lohr KM*, Masoud ST, Salahpour A, Miller GW. Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease. Eur J Neurosci. 2017 Jan;45(1):20-33. doi: 10.1111/ejn.13357. Review. PMID: 27520881.
Stout KA*, Dunn AR, Lohr KM, Alter SP, Cliburn RA, Guillot TS, Miller GW. Selective Enhancement of Dopamine Release in the Ventral Pallidum of Methamphetamine-Sensitized Mice. ACS Chem Neurosci. 2016 Oct 19;7(10):1364-1373. PMID: 27501345.
Dunn AR*, Stout KA, Lohr KM, Hoffman C, Bernstein AI, Li Y, Wang M, Sgobio C, Sastry, N, Cai H, Caudle WM, Miller G.W. (2017) Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson’s disease. Proceedings of the National Academy of Sciences. Mar 14;114(11):E2253-E2262. PMC5358362.
Niedzwiecki MM*, Samant P, Walker DI, Tran V, Jones DP, Prausnitz MR, Miller GW. Human Suction Blister Fluid Composition Determined Using High-Resolution Metabolomics. Analytical Chemistry 2018 90 (6), 3786-3792. PMC5863097.
Niedzwiecki MM, Walker DI, Vermeulen R, Chadeau-Hyam M, Jones DP, Miller GW. The Exposome: Molecules to Populations. Annu Rev Pharmacol Toxicol. 2018 Aug 10. doi: 10.1146/annurev-pharmtox-010818-021315. Epub 2018 Aug 10. PMID: 30095351.
Stout KA, Dunn AR, Hoffman C, Miller GW. The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance. ACS Chem Neurosci. 2019 Sep 18;10(9):3927-3938. doi: 10.1021/acschemneuro.9b00351. Epub 2019 Aug 23. PMID:31394034.
Cheung AC, Walker DI, Juran BD, Miller GW, Lazaridis KN. Studying the Exposome to Understand the Environmental Determinants of Complex Liver Diseases. Hepatology. 2019 Nov 8. doi: 10.1002/hep.31028. Epub 2019 Dec 24. Review. PMID:31701542.