2020 AwardeesDana Dolinoy, Ph.D.
Academic Title: NSF International Chair of Environmental Health Sciences, Professor of Environmental Health Sciences, Professor of Nutritional Sciences
Institution: University of Michigan School of Public Health
Project Title: Environmental Epigenomics and Precision Environmental Health
Grant Number: R35ES031686-01
Research:Dana Dolinoy, Ph.D., studies how early life environmental exposures lead to changes in DNA and contribute to disease. She creates new tools to study wide-ranging epigenetic markers in multiple tissue and cell types, both animal and human. Epigenetic marks are changes in the chemical nature of DNA that affect cellular functions. Dolinoy and her team are identifying changes in DNA, non-coding RNA, chromatin structure, and gene expression after exposure to metals or plasticizers. They plan to identify epigenetic markers of environmental exposure and disease susceptibility. She also plans to develop a suite of epigenetic editing tools that overcome limitations of current technologies. Her long-term goal is to develop human epigenome editing as a therapeutic tool to treat environmental and epigenetic diseases including cancer.
Joann B. Sweasy, Ph.D.
Academic Title: Interim Director, Cancer Center Division; Professor, Cellular and Molecular Medicine; Professor, Radiation Oncology; Associate Director, Basic Sciences, University of Arizona Cancer Center
Institution: University of Arizona
Project Title: Aberrant DNA Repair and Lupus
Grant Number: R35ES031708-01
Research: More than one million Americans suffer from Systemic Lupus Erythematosus (SLE or lupus), an autoimmune disease for which there is no cure. Joann Sweasy, Ph.D., studies how environmental exposures and gene-environment interactions influence lupus development. Her research into the causes of cancer led her to the surprising discovery that mice, which do not have the capacity to repair damaged portions of their DNA, develop lupus. In collaboration with other colleagues, Sweasy also identified a series of related human gene variants that are common in people with lupus. Combining this knowledge, she plans to construct mouse models with abnormal DNA repair genes like those found in people with lupus. These innovative models will allow Sweasy to study how genetic predisposition and environmental exposures together contribute to lupus with the goal of improving disease treatment.
Bennett Van Houten, Ph.D.
Academic Title: Professor, Pharmacology and Chemical Biology
Institution: University of Pittsburgh
Project Title: Watching Cooperative Interactions Between Base and Nucleotide Excision Repair Proteins
Grant Number: R35ES031638-01
Research: Ben Van Houten, Ph.D.’s research uses ground-breaking technologies to give new and unique information as to how common forms of DNA damage are detected and repaired in a living cell. This project will generate single cell, molecular-level views of the complex process of repair of DNA damage in living cells. DNA lesions form after exposure to genotoxic agents including environmental pollutants. DNA damage, if unrepaired, can cause cancer, premature aging, neurodegeneration, and other diseases. Van Houten’s team combines biochemistry, single molecule analysis, and cutting-edge cell biology tools to provide unprecedented optical views of the process. His team will develop high-resolution methods to enable the ability to watch individual repair proteins in purified systems and living cells as they interact and process DNA damage sites in real-time. Van Houten will also examine how DNA repair proteins work with other enzyme proteins to influence gene expression.
Yinsheng Wang, Ph.D.
Academic Title: Distinguished Professor and Donald T. Sawyer Endowed Founder's Chair in Chemistry
Institution: University of California, Riverside
Project Title: Chemical Biology of DNA and RNA Alkylation
Grant Number: R35ES031707-01
Research: Compounds that can chemically modify DNA and RNA through alkylation are common in the environment. Alkylation, a type of damage that creates lesions in DNA, can alter gene expression and lead to disease. Yinsheng Wang, Ph.D., studies how alkylated DNA lesions affect DNA stability and how cells sense and repair these lesions. He also studies how modifications in RNA contribute to neurological diseases. To explore these questions, his team studies how specific proteins influence expression of genes with DNA lesions. They also identify DNA damage recognition proteins and their role in DNA damage response signaling and repair. Wang draws on his expertise in DNA damage and repair to use cutting-edge technologies to answer these questions. This project should increase understanding about human health consequences from exposure to alkylating agents and other environmental toxicants. This knowledge may, in turn, help the prevention and treatment of human diseases arising from nucleic acid alkylation.
Donna Zhang, Ph.D.
Academic Title: Musil Family Endowed Chair in Drug Discovery; Associate Director of Superfund Research Program; Professor, Pharmacology and Toxicology
Institution: University of Arizona
Project Title: Nrf2 Transcription Factors in Environmental Stress and Disease Intervention
Grant Number: R35ES031575-01
Research: Exposure to arsenic affects 160 million people worldwide leading to cancer and diabetes. Donna Zhang, Ph.D. studies how arsenic-related diseases develop with the goal of identifying new pharmaceuticals to treat or prevent health effects resulting from arsenic exposure. The protein Nrf2 helps regulate the cellular stress response and reduces the damage from arsenic and recognition of its role is the basis for a number of pharmaceuticals used to prevent cancer. However, Dr. Zhang discovered a “dark side” of Nrf2; that constant stimulation can drive cancer progression and resistance to therapy. The goals of her project, then, are to characterize the molecular basis of diseases associated with arsenic.
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 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, Ph.D.
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.