Research Projects

Network for Exposomics in the U.S. (NEXUS) Coordinating Center organizes and stimulates research on the human exposome—the cumulative measure of environmental exposures and corresponding biological responses.

NEXUS Coordinating Center is led by Gary Miller, PhD, Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences, at Columbia University Mailman School of Public Health; Chirag Patel, PhD, Associate Professor of Biomedical Informatics at Harvard Medical School; and Rima Habre, ScD, Associate Professor of Population and Health Sciences at the University of Southern California.

Its members include many of the leading researchers in the emerging field, from City University of New York, Delaware State, Emory, Johns Hopkins University, Morehouse, Pacific Northwest National Laboratory, University of California San Francisco, Harvard, University of North Carolina, University of Southern California, and Yale. NEXUS will establish a framework and best practices for exposomics analysis of biological and environmental samples, develop a framework for geospatial-based exposomics studies of environmental and social influences on health and disease, and create a comprehensive exposomics digital framework to support precision environmental health. It will also engage with multidisciplinary academic, community, and industry partners, in the U.S. and around the world, and will support bootcamps, conferences, and other learning opportunities to grow exposomics as a field, with attention to overcoming socioeconomic inequities.

• Gary Miller, Randolph Singh

Partners

• Rima Habre
• Thomas Hartung
• Thomas Metz
• Chirag Patel
• Krystal Pollitt
• Fenna Sille
• Marina Sirota
• Carmen Marsit
• Arcot Rajasekar
• Doug Walker

IndiPHARM: individual metabolome and exposome assessment for pharmaceutical optimization, funded by ARPA-H. IndiPHARM researchers will develop a platform to measure hundreds of drugs and their metabolites and thousands of chemicals derived from the environment, diet, and lifestyles.

Ultimately, the goal is to optimize how medications work by equipping individuals and their doctors with a tool that can answer the question, “Is the drug or combination of drugs I am taking optimized for me?” The platform will also help pharmaceutical suppliers, insurance payors, and providers to anticipate and reduce adverse therapeutic effects, including side effects and inefficiencies, in both individuals and populations.

Led by Gary Miller, PhD, Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences, at Columbia University Mailman School of Public Health, IndiPHARM also includes investigators from the Mayo Clinic, Harvard Medical School, Emory University, Brown University, and the Jackson Laboratory.

• Gary Miller, Randolph Singh

Partners

• Arjun Athreya
• Serge Cremers
• Young-Mi Go
• George Hripcsak
• Xin Hu
• Dean Jones
• Kostas Lazaridis
• Shuzhao Li
• Chirag Patel
• Kurt Pennell
• Doug Walker

This overarching effort is designed to develop and optimize methods to measure exogenous and endogenous small molecules in human samples. This work is based in the Center for Innovative Exposomics with numerous collaborations across Columbia and throughout the world. Some of the applications are listed below, but there are several other examples including Parkinson’s disease and chronic kidney disease. 

• Gary W. Miller
• Randolph Singh
• Yunjia Lai
• Jocelyn Dicent
• Carolina Duarte Hospital
• Vrinda Kalia 

Research Infrastructure for Environmental Exposure Assessment in Europe funded by the European Strategy Forum for Research Infrastructure (ESFRI)-European Commission.

Building off the decades of work by Richard Mayeux and his team, this effort involves two projects conducted in collaboration with partners in Neurology. WHICAP is a community-based study of aging based in Washington Heights. EFIGA is a project based in the Dominican Republic. The Miller team and the Exposomics Laboratory is conducting high-resolution mass spectrometry to provide metabolomics and exposomics data to help better understand the development and progression of Alzheimer’s disease.

• Gary W. Miller
• Vrinda Kalia
• Randolph Singh
• Paolo Reho

Funding: NIA RF1 AG066107-01A1 and R01 AG067501
Collaboration: Dr. Richard Mayeux and Dr. Badri Vardarajan 

This effort is based upon a longstanding collaboration with the Mayo Clinic. The Center for Innovative Exposomics supports this project in collaboration with the Miller Laboratory. The Center provides expertise in high-resolution mass spectrometry to study primary sclerosing cholangitis and primary biliary cholangitis. 

• Gary W. Miller

Funding: RC2DK118619 and R01 DK126691
Collaboration: Dr. Kostas Lazaridis and Dr. Dean Jones

Team SAMBAI aims to create an unprecedented resource to define the factors that cause and influence disparate outcomes in diverse underserved populations. This project will look at social, environmental, biological, and genetic determinants of disease is the African diaspora. Dr. Miller’s team will lead Work Package 2 to conduct the exposomics analysis. 

• Gary W. Miller
• Randolph Singh
• Howie Wu
• HuiChen Wu 
• Kam-Meng Tchou-Wong

Funding: Cancer Grand Challenge-SAMBAI funded by Cancer Research UK and the National Cancer Institute
Collaboration: Dr. Melissa Davis and SAMBAI

This project examines the role of vesicular storage of dopamine in Parkinson’s disease pathogenesis. It builds upon the lab’s work of the vesicular monoamine transporter 2 (VMAT2; SLC18A2) and the synaptic vesicle glycoprotein 2C (SV2C). The premise is that poor handling of dopamine increases vulnerability of the dopamine neuron in Parkinson’s disease. A range of environmental chemicals disrupt the ability of vesicles to store dopamine, which may contribute to the onset and progression of the disease.

• Gary W. Miller
• Meghan Bucher
• Haejung Chung

Partners: Ali Salahpour
Funding: NIEHS R01 ES023839

Our laboratory has a long history of studying mechanisms of neurotoxicity using a range of tools. Over the past few years we have been using the model organism C. elegans to study how various chemicals disrupt neuronal function. 

• Gary W. Miller
• Meghan Bucher
• Joceyln Dicent
• Carolina Duarte Hospital

Funding:  NIEHS R01 ES023839

Our work on SV2C was initiated by the observation that the molecule appears to mediate the counterintuitive ability of smoking and nicotine to prevent Parkinson’s disease. This project builds upon the work on SV2C in PD. The lab previously showed that SV2C regulated the storage and release of dopamine in the nigrostriatal system. The team is now trying to develop pharmaceutical agents to improve outcomes in Parkinson's disease.

• Gary W. Miller
• Meghan Bucher
• Haejung Chung 

Partners: Ali Salahpour
Funding: SPARK-NS