Manish Arora, Ph.D.
Academic Title: Professor of Environmental Medicine & Public Health, and Dentistry; Co-Director of the Senator Frank R. Lautenberg Environmental Health Sciences Laboratory
Institution: Icahn School of Medicine at Mount Sinai
Project Title: Early Warning Systems for Childhood and Adult Disorders
Grant Number: R35ES030435
Research: Many scientific fields, such as physics, psychology, and biology, develop deep theories to explain their domain of the world and also make predictions of yet unobserved phenomenon. The recent observation of the black hole, predicted decades ago by the theory of general relativity, is one such example. Environmental health sciences for the most part operate differently; typically, information on various components of the environment is collected and linked to health outcomes using statistical tools. Manish Arora Ph.D. along with Paul Curtin Ph.D. and their team have proposed a theory – the Biodynamic Interface – that suggests the existence of a temporally dynamic interface between the environment and human physiology. By applying this theory and newly developed technology to disorders that appear at all stages of life, the team will develop early warning systems to predict, and perhaps even prevent, diseases decades before any clinical signs are apparent.
Bruce Hammock, Ph.D.
Academic Title: Distinguished Professor of Entomology; Member, University of California, Davis (UCD) Comprehensive Cancer Center; Director, NIEHS-UCD Superfund Research Program
Institution: University of California, Davis
Project Title: Bioactive Lipids as Effectors and Indicators of the Deleterious Effects of Environmental Exposure on Chronic Diseases
Grant Number: R35ES030443
Research: Epoxyfatty acids (EpFA) including epoxides of omega 3 fatty acids are part of a natural regulatory pathway that maintains health. Bruce Hammock, Ph.D., is studying how chemical exposures and other factors disrupt this pathway sometimes leading to disease. He is also developing approaches to stabilize EpFAs to prevent and treat diseases. Biochemical stress pathways within cells, such as the endoplasmic reticulum (ER) stress pathway, are interconnected with fatty acid regulation. Hammock is developing tools and methods to measure ER stress and inhibit enzymes that break down EpFAs. In animal models, some EpFA breakdown inhibitors are beneficial in treating pain, cancer, Parkinson’s disease, and other diseases. Hammock is working to better understand these processes and apply the knowledge to improve human health.
Patricia Opresko, Ph.D.
Academic Title: Associate Professor, Department of Environmental and Occupational Health
Institution: University of Pittsburgh
Project Title: Excision Repair of Environmental Telomere Damage
Grant Number: R35ES030396
Research: DNA is packaged into chromosomes, and telomeres at the end of chromosomes play important roles in maintaining normal cell functions. Shortened or damaged telomeres contribute to cancer and diseases associated with aging. Patricia Opresko, Ph.D., worked with collaborators to develop a highly innovative tool, which uses light and small molecule probes to selectively cause DNA lesions at telomeres. The technology allows her research team to target specific DNA sequences so they can understand how telomere damage occurs and how it leads to disease. Opresko will also target telomere damage to specific organs and tissues to study the impacts on health in animal models with a goal of preventing and treating diseases.
Kim Tieu, Ph.D.
Academic Title: Professor and Interim Department Chair, Department of Environmental Health Sciences
Institution: Florida International University
Project Title: Toxicant-induced Neurotoxicity Mediated by Glia-Neuron and Gene-Environment Interactions in Parkinson’s Disease
Grant Number: R35ES030523
Research: Kim Tieu, Ph.D., has been studying interactions between genes and environmental exposures in Parkinson’s disease. This project will focus on the role of dynamin related protein-1 (Drp1) in the disease. Drp1 is a protein that plays a role in the splitting of mitochondria, the energy-producing component in cells. However, this protein has been proposed in recent years to play a role in brain disorders such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease. Based on his recent unexpected discovery of a new function of Drp1, Tieu will research its role in neurotoxicity by looking at neural cell interactions and gene-environment interactions. His team will also explore the role of Drp1 in toxicity after exposure to manganese or pesticides alone, or in combination with gut bacteria. His research on Drp1 will contribute to his long-term goal of developing new therapeutics for Parkinson’s Disease.
Wen Xie, M.D., Ph.D.
Academic Title: Joseph Koslow Endowed Chair and Professor, Department of Pharmaceutical Sciences
Institution: University of Pittsburgh
Project Title: Xenobiotic Receptors in Mediating the Environmental Effects on Human Disease and Morbidity
Grant Number: R35ES030429
Research: Wen Xie, M.D., Ph.D., is studying receptors that can bind xenobiotic factors, which come from outside the body, such as environmental chemicals. The same receptors can also bind factors that exist naturally inside the body, or endobiotics. He is leading a transdisciplinary team of researchers and clinician scientists to study how xenobiotic receptors regulate the ability to breakdown environmental chemicals, and how they regulate normal body functions. Xie plans to use the information to design strategies to target these receptors for new therapeutics to prevent and treat diseases, and to reduce toxicity from environmental exposures.
Mark Zylka, Ph.D.
Academic Title: Director, Neuroscience Center; W. R. Kenan, Jr. Distinguished Professor, Department of Cell Biology and Physiology
Institution: University of North Carolina at Chapel Hill
Project Title: Environmental-use Chemicals that Target Pathways Linked to Autism and Other Neurodevelopmental Disorders
Grant Number: R35ES028366
Research: This project focuses on interactions between genetics and environmental exposures that may contribute to neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder. Mark Zylka, Ph.D., is leading a three-pronged approach to identify exposure risks and susceptible individuals. First, his team will identify environmental chemicals and mixtures that target molecular neurodevelopmental pathways. Second, a network of researchers will characterize real-world exposures to these chemicals. Third, using specific gene variants that have been linked to autism, the research team will study genetic susceptibility to toxicity from chemical exposures in animals to help identify and confirm susceptibility genes in humans, and how these genes influence toxicit.
Christopher A. Bradfield, Ph.D.
Academic Title: Professor
Institution: University of Wisconsin-Madison
Project Title: The PAS Sensor Family and Human Health
Grant Number: R35ES028377
Research: Proteins with Per-Arnt-Sim (PAS) domains are found in mammalian sensors for foreign substances, light, and oxygen. Members of this sensor family of proteins also function in signaling pathways important for mammalian development. Bradfield is leading a transdisciplinary team of population health scientists, geneticists, molecular biologists, and clinician scientists to study the role of PAS sensors in environmentally-influenced diseases such as cancer and obesity. Their overarching goals are to increase understanding of PAS family signaling pathways and to develop interventions and therapeutic strategies to improve human and environmental health.
Matthew C. Cave, M.D.
Academic Title: Associate Professor of Medicine
Institution: University of Louisville
Project Title: Environmental Liver Disease
Grant Number: R35ES028373
Research: Liver disease is a major health problem, affecting many people worldwide. To enhance liver disease research, Cave is leading efforts to establish the Environmental Liver Disease Revolutionizing Innovative, Visionary Environmental Health Research Program (ELD-RIVER). The vision is to establish ELD-RIVER as a global hub for integrative environmental liver disease research. Basic scientists, epidemiologists, and physicians will investigate roles of chemical exposures and nutrient-chemical interactions in liver disease in humans and animal models. Initially they will focus on endocrine- and metabolism-disrupting chemicals. Their goals include development of new biomarkers, treatments, and clinical practice guidelines to improve treatment and prevention of liver disease.
Myron Goodman, Ph.D.
Academic Title: Professor, Department of Biological Sciences and Chemistry
Institution: University of Southern California
Project Title: Hypermutation in Bacteria and Humans
Grant Number: R35ES028343
Research: DNA hypermutation processes, which can generate a high frequency of mutations in organisms, can be beneficial because they promote survival following DNA damage and signal antibody responses to infections. Goodman is using cutting-edge biochemical and high-resolution microscopy methods to visualize changes in the shape of a DNA polymerase involved in hypermutation in both disease causing and non-disease-causing bacteria. Goodman hopes to understand how the process occurs. He is also investigating the regulation of hypermutation that leads to the generation of diverse antibodies in response to infections in humans. Building on this research, Goodman’s team is developing technologies to create antibodies that will bind quicker and better to any antigen in cell culture. Such technologies could have substantial implications for medical therapeutics.
Gary Joseph Patti
Academic Title: Michael and Tana Powell Associate Professor
Institution: Washington University
Project Title: Developing Metabolomic Technologies to Advance Environmental Exposure Analysis
Grant Number: R35ES028244
Research: Metabolomics is the comprehensive profiling of small molecules. When doing a metabolomics experiment, only a small number can be identified by their chemical structure. A major limitation has been the noise characteristic of metabolomic datasets, or false signals that may mask a true signal in the data. Patti’s team will use newly developed technologies to remove this noise, thereby facilitating the naming of metabolite signals. By using annotated datasets as a reference, Patti’s lab will analyze zebrafish exposed to toxic compounds to identify biochemical pathways affected by the exposures. Beyond this specific application, the metabolomic tools developed will enhance researchers’ ability to harness information from metabolomic analyses.
Gary H. Perdew, Ph.D.
Academic Title: John T. and Paige S. Smith Professor in Agricultural Sciences and the Director of the Center for Molecular Toxicology and Carcinogenesis
Institution: Pennsylvania State University – University Park
Project Title: Activation of the Ah Receptor and Epithelial Integrity
Grant Number: R35ES028244
Research: Cells lining the skin and gut, or epithelial barriers, play important roles in disease processes and prevention including immune surveillance. Leading a multi-disciplinary team, Perdew is studying the aryl hydrocarbon receptor (AhR) as a central regulator of barrier tissue function and repair. They are identifying naturally occurring compounds in the diet and the gut that bind to the AhR, and proteins that form AhR regulatory complexes. Perdew is also studying the role of the AhR in immune regulation and barrier functions in skin and in the gut to gain understanding that may translate to new therapeutic approaches.
Brandon Lee Pierce, Ph.D.
Academic Title: Associate Professor
Institution: University of Chicago
Project Title: Arsenic and the Human Genome: Susceptibility and Response to Exposure
Grant Number: R35ES028379
Research: More than one hundred million people worldwide consume arsenic-contaminated drinking water, increasing risks for adverse health conditions including cancer. Previous genetic studies have identified gene variants and other genome features (e.g., telomere length) that render some people more susceptible to arsenic toxicity. To identify additional gene-environment relationships, Pierce is leading development of a large genomic data resource in the context of an ongoing study in Bangladesh. Pierce aims to identify features of the human genome, both inherited and acquired, that reflect susceptibility to arsenic toxicity. This work may reveal mechanisms of toxicity and susceptibility and provide strategies for identifying high-risk individuals and reducing their exposure.
Graham Walker, Ph.D.
Academic Title: Professor of Biology, American Cancer Society Professor, and Howard Hughes Medical Institute Professor
Institution: Massachusetts Institute of Technology
Project Title: Mechanism of Eukaryotic Environmental Mutagenesis
Grant Number: R35ES028303
Research: DNA damage arises during responses to environmental exposures, and during the initiation and treatment of cancer. Translesion synthesis (TLS) is one process by which organisms respond to DNA damage while maintaining functioning, and ironically may also result in DNA mutations. Walker’s lab focuses on mechanisms of TLS to better understand the process and to improve chemotherapy. To modify these processes, his team is developing new inhibitors of TLS and is testing them in cell lines and mouse models of human cancer. By using state-of-the-art approaches, Walker and his team will provide new detailed functional insights into the complex protein interactions during TLS.
Michael B. Yaffe, M.D., Ph.D.
Academic Title: David H. Koch Professor of Science, professor of biology and biological engineering, director of the MIT Center for Precision Cancer Medicine, director of the MIT Koch Institute Clinical Investigator Program
Institution: Massachusetts Institute of Technology
Project Title: Protein Kinase Signaling in the Genotoxic Stress Response
Grant Number: R35ES028374
Research: Responses to DNA damage and inflammation can lead to the development of cancer. To better prevent and treat cancer, it is important to understand the regulation of protein kinase signaling pathways. Yaffe identified the dual role of the p38MAPK-MAPKAP kinase-2 pathway, which functions in both DNA damage response and inflammation. Recently Yaffe and others have also identified RNA damage response pathways that cause cell damage and death. For this project, Yaffe and his team are studying the regulation and effects of these pathways in epithelial tissues and testing mechanistic models in animal and computational human studies.