Miller Lab
Location and Contact Information
- Office Phone 212-342-1260
- Lab Phone 212-305-1205
Principal Investigator
Neurotransmitter Storage
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.
Exposome
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/(link is external and opens in a new window)
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.
Lab Members
Lab Members
Meghan Bucher
- Postdoctoral Research Scientist
Meghan Bucher, PhD is a Postdoctoral Research Fellow in the Department of Environmental Health Sciences. She joined the Mailman School of Public Health at Columbia University in January 2020 after receiving a PhD in Neuroscience from the University of Pittsburgh. Her current work utilizes in vitro and Caenorhabditis Elegans models to understand biological, toxicological, and pharmacological regulators of dopamine neuron homeostasis with relevance for diseases and disorders of dopamine systems including ADHD, substance use disorder, and Parkinson’s disease. In addition, Dr. Bucher has contributed to literature reviews advocating for the use of Exposomics as a tool to understand how environmental exposures contribute to sex- and gender-specific health outcomes.
Vrinda Kalia
- Associate Research Scientist
Vrinda’s expertise is metabolomics, bioinformatics and statistical analysis.
Yunjia Lai
- Postdoctoral Research Scientist
Yunjia Lai, Ph.D., is a Postdoctoral Research Scientist in the Miller lab. She is broadly interested in elucidating gene-environment interactions and microbiome influences linked to neurological disorders. She received her PhD at UNC Chapel Hill, where she developed analytical chemistry (high-resolution mass spectrometry-based) and systems omics approaches to probing environmental and gut microbial effects on humoral gut-brain axis. In the Miller Lab, her work continues to focus on exposome analysis, microbiomics, and neurotoxicant-oriented toxicological research topics to elucidate the environmental drivers of neurodegeneration, including Parkinson's disease. Yunjia is also involved in the BCL Core Lab thanks to her background as analytical chemist and toxicologist and her extensive research experience in leveraging high-resolution mass spectrometry technologies for systems toxicological insights. She develops novel omics assays and informatics pipelines.
Carolina Duarte Hospital
- Postdoctoral Research Scientist
Carolina Duarte Hospital, PhD, is a Postdoctoral Research Scientist in the Department of Environmental Health Science. She holds a Ph.D. in Toxicology from the Université Paris Cité, where she specialized in studying Mechanisms of toxicity of succinate dehydrogenase inhibitors (SDHi) fungicides: impact on mitochondrial functions and metabolic reprogramming in human colon epithelial cells. Since May 2023, Carolina has been conducting her research at Miller's Lab in the Mailman School of Public Health. Her current work primarily revolves around the exposomic approach to evaluating exogenous toxicants. Additionally, she is actively engaged in research utilizing Extracellular Vesicles (EVs) for exposomics investigations. Carolina's research interests extend to investigating the correlation between exposure to environmental toxicants and neurodegenerative diseases, with a particular focus on Parkinson's and Alzheimer's diseases. Through her research endeavors, she aims to unravel the intricate toxicological mechanisms underlying these neurological impairments, thereby contributing significantly to advancing our understanding of the intricate connections between environmental factors and neurological health.
Paolo Reho
- Postdoctoral Research Scientist
Paolo Reho, PhD, is a Postdoctoral Research Scientist in the Department of Environmental Health Sciences. He earned his PhD in Genetics, Molecular, and Cellular Biology from the University of Pavia (Italy). In 2020, he started his first postdoctoral experience at the NIH - National Institute of Neurological Disorders and Stroke (Bethesda, MD). Dr. Reho has dedicated his research on understanding the genetic and epigenetic factors contributing to neurodegeneration, with a specific focus on Lewy body dementia and multiple system atrophy. He recently elucidated the association of rare pathogenic mutations and specific epigenetic modulations with the etiology of Lewy body dementia. In October 2023, Dr. Reho joined the Mailman School of Public Health at Columbia University. Here, he applies multi-omics computational approaches to investigate the intricate interplay between genetics and exposomics in neurodegenerative disorders such as Alzheimer’s disease, as well as individual drug responses.
Jocelyn Dicent
- Student
Jocelyn is a 3rd-year PhD student in Environmental Health Sciences in Dr. Gary Miller’s lab. She entered the program 2021 with a BS in Chemistry from Yale University. At Yale, her research primarily focused on organic synthesis in Dr. Craig Crews’ lab. She also spent time doing bioengineering research using C. elegans and microfluidic devices in Dr. Hang Lu’s lab at Georgia Tech. After graduating, she worked at NYU in Dr. Kurunthachalam Kannan’s lab. She focused on analyzing concentrations of metabolite organophosphate esters (mOPEs) in urine using mass spectroscopy. Her current research interests include neurotoxicology, metabolomics, and using the C. elegans models to explore the outcomes of toxins or toxicants on health. Currently, she is working on studying trichloroethylene (TCE) in the context of Parkinson’s Disease incidence using metabolomics, the C. elegans model, molecular biology, and basic science approaches for her dissertation work.
Hae Chung
- Lab Manager
Hae Jung Chung joined the Miller lab in December 2022. She manages the day-to-day operations of the Miller lab, ensuring that all personnel have access to the resources they need to complete experiments. Additionally, for her research project, Hae Jung uses cell culture models to investigate the function of two proteins in Parkinson’s Disease, the vesicular monoamine transporter 2 (VMAT2) and the synaptic vesicular glycoprotein 2C (SV2C). Hae Jung has been at Columbia University for 25 years. Before joining the Miller lab, she was in the Steinberg lab, studying the Beta1-Adrenergic Receptor, a transmembrane protein expressed predominantly in cardiac tissue. Hae Jung received her BS and MS in Nutrition Science at Ewha Womans University, Seoul, Korea, her M.A. in Nutrition Science at Kansas State University, Manhattan, Kansas, and her MS in Acupuncture at Tri -tate College of Acupuncture, New York, NY.
Yolanda Durant
- Senior Administrative Coordinator
Scheduler for Dr. Gary Miller.
Select Publications
Lefèvre-Arbogast S, Chaker J, Mercier F, Barouki R, Coumoul X, Miller GW, David A, Samieri C. The chemical exposome of neurodegenerative diseases. Nature Neuroscience. May 1, 2024, in press.
Zhao Y, Lai Y, Konijnenberg H, Huerta JM, Vinagre-Aragon A, Sabin JA, Hansen J, Petrova D, Sacerdote C, Zamora-Ros R, Pala V, Heath AK, Panico S, Guevara M, Masala G, Lill CM, Miller GW, Peters S, Vermeulen R. Association of coffee consumption and prediagnostic caffeine metabolites with incident Parkinson Disease in a population-based cohort. Neurology. 23;102(8):e209201, 2024
Bucher ML, Dunn AR, Bradner JM, Egerton KS, Burkett JP, Johnson MA, Miller GW. Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity. European Journal Neuroscience. Mar 26, 2024.
Walker DI, Juran BD, Cheung AC, Schlicht EM, Liang Y, Niedzwiecki M, LaRusso NF, Gores GJ, Jones DP, Miller GW, Lazaridis KN. High-resolution exposomics and metabolomics reveal specific associations in cholestatic liver diseases. Hepatology Communications. May;6(5):965-979, 2022.
Koelmel JP, Xie H, Price EJ, Lin EZ, Manz KE, Stelben P, Paige MK, Papazian S, Okeme J, Jones DP, Barupal D, Bowden JA, Rostkowski P, Pennell KD, Nikiforov V, Wang T, Hu X, Lai Y, Miller GW, Walker DI, Martin JW, Godri Pollitt KJ. An actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry. Exposome. Aug 25;2(1):osac007, 2022.
Kalia V, Niedzwiecki MM, Bradner JM, Lau FK, Anderson FL, Bucher ML, Manz KE, Schlotter AP, Fuentes ZC, Pennell KD, Picard M, Walker DI, Hu WT, Jones DP, Miller GW. Cross-species metabolomic analysis of tau- and DDT-related toxicity. PNAS Nexus. May 3;1(2):pgac050. doi: 10.1093/pnasnexus/pgac050, 2022.
Hu X, Walker DI, Liang Y, Smith MR, Orr ML, Juran BD, Ma C, Uppal K, Koval M, Martin GS, Neujahr DC, Carmen J. Marsit CJ, Go YM, Pennell KD, Miller GW, Lazaridis KN, Jones DP. A scalable workflow for the human exposome. Nature Communications. Sep 22;12(1):5575, 2021.
Liu KH, Lee CM, Singer G, Bais P, Castellanos F, Woodworth MH, Ziegler TR, Kraft CS, Miller GW, Li S, Go YM, Morgan ET, Jones DP.. Large-scale, enzyme-based xenobiotic identification for exposomics. Nature Communications. Sep 14;12(1):5418, 2021.
David A, Chaker J, Price EJ, Bessonneau V, Chetwynd A,Vitale CM, Klanova J, Walker DI, Antignac JP, Barouki R, Miller GW. Towards a comprehensive characterisation of the human internal chemical exposome: challenges and perspectives. Environment International. Nov;156:106630, 2021.
Vecchio LM, Sullivan P, Dunn AR, Bermejo MK, Fu R, Masoud ST, Gregersen E, Urs NM, Nazari R, Jensen PH, Ramsey A, Goldstein DS, Miller GW, Salahpour A. Enhanced tyrosine hydroxylase activity induces oxidative stress, causes accumulation of autotoxic catecholamine metabolites, and augments amphetamine effects in vivo. Journal of Neurochemistry. Aug;158(4):960-979, 2021.
Bradner JM, Kalia V, Lau FK, Sharma M, Bucher ML, Johnson M, Chen M, Walker DI, Jones DP, Miller GW. Genetic or toxicant-induced disruption of vesicular monoamine storage and global metabolic profiling in Caenorhabditis elegans. Featured Article. Toxicological Sciences. 2021 Feb 4:kfab011.
Mor DE, Sohrabi S, Kaletsky R, Keyes W, Tartici A, Kalia, V*, Miller, GW, Murphy CT. Metformin rescues Parkinson’s disease phenotypes caused by hyperactive mitochondria. Proceedings of the National Academy of Sciences 117: 26438, 2020.
PP Samant, MM Niedzwiecki, N Raviele, V Tran, J Mena-Lapaix, DI Walker, EI Felner, DP Jones, GW Miller, MR Prausnitz. Sampling interstitial fluid from human skin using a microneedle patch. Science Translational Medicine. 12(571): eaaw0285, 2020.
Vardarajan B, Kalia V*, Manly J, Brickman A, Reyes-Dumeyer D, Lantigua R, Ionita-Laza I, Jones DP, Miller GW, Mayeux R. Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity. Alzheimer’s Dement (NY). 6(1):e12025, 2020.
Vermeulen R, Schymanski E, Barabási AL, Miller GW. The exposome and health: where chemistry meets biology. Science, 367:392-396, 2020
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