Genes, Environment and Precision Health
Environment, genome and epigenome interactions, and health outcomes
Mission statement: Research focuses on the interactions between the environment, the genome, and the epigenome in influencing disease susceptibility, and the manipulation of these mechanisms to improve lifelong health. Specific interests include the effects and underlying mechanisms of environmental exposures in early life and in adulthood, gene by environment interactions, epigenetic biomarkers that predict different sensitivities and disease outcomes, and environmental carcinogenesis.
Main goal: To promote the exchange of ideas and the sharing of expertise on experimental designs, technologies, and concepts to understand the interactions between the environment, the genome, and the epigenome.
Our laboratory studies how environmental exposures during early life affect health and disease in adulthood. Using the mouse as a model, we investigate the molecular mechanisms underlying these programming effects, focusing particularly on epigenetic changes that occur in response to an exposure. We employ high-throughput techniques (next generation sequencing) to identify early epigenetic and transcriptomic changes, and aim to understand the processes through which these lead to an altered phenotype in later life.
The Genomic Sciences Laboratory (GSL) is a University Shared Research Facility operated under the guidance of the NC State Office of Research & Innovation. The ongoing GSL mission is to provide cutting edge genomics and Next Generation Sequencing services to NC State faculty, Center for Human Health & Environment members and the greater scientific community. As the lead Genomics Navigator for the CHHE Systems Technology Core, my role is to provide expert guidance and enhanced in-person support to Center members seeking to utilize genomic approaches in their research.
Dr. Binder’s research focuses on people’s concerns related to science, technology, and risk and understanding how people make sense of these topics. His published research has focused on a variety of issues, from public opinion of climate change, to social media conversations about nuclear power, and to community controversies surrounding the building of a new national biological research facility in the mainland United States. He coordinates scholarly exchanges of ideas between Center members and other researchers at NC State, consults with Center members on the integration of community engagement into their research projects, and trains Center members in social science perspectives on environmental health research.
Dr. Shobhan Gaddameedhi received his PhD from North Dakota State University and pursued his post-doctoral training at the University of North Carolina. His laboratory studies the mechanisms by which the circadian clock regulates the environmental health outcomes through ‘gene-environment’ interactions and identifies the molecular mechanisms by which circadian disruption influences genomic instability, skin and cardiovascular toxicity, and environmental carcinogenesis outcomes. He hopes to use these findings to identify disease preventive mechanisms and therapeutic treatments for environmental diseases.
Dr. Gookin is nationally recognized for her expertise in gastroenterology with a special emphasis on infectious causes of feline diarrheal disease. Dr. Gookin and her colleagues are credited with identification of Tritrichomonas foetus as a previously unrecognized cause of diarrhea in domestic cats and have dedicated over 15 years of research effort into establishing the pathogenicity, means for diagnosis, worldwide significance, and an effective treatment for this infection.
A long term goal of our laboratory is to delineate the significance of genetic risk factors in the development and etiology of prostate and ovarian cancer in multiethnic populations. Together with my collaborators at NCCU, UNC-CH, DUMC, and NIEHS/NIH, we have employed genomics, epidemiological and functional approaches to identify and study biomarkers that impact susceptibility to disease and environmental response to toxins. We have focused on genes from the drug metabolizing enzyme super family UDP-glucuronosyltransferase (UGT) which play an important role in steroid hormone and xenobiotic metabolism. Studies of DNA sequence variants of the UGT2B and UGT2A subfamilies show suggestive associations with risk of prostate and ovarian cancer in individuals of African ancestry. We have developed a null UGT2 mouse models and now stand ready to collaborate with scientists in the CHHE at NCSU to determine the translational significance of variant UGT2 alleles and their consequences in prostate and ovarian cancer health disparities.
In order to maintain genomic integrity and prevent cancer, cells must respond to DNA damage by engaging the DNA damage. We use a combination of cellular-based systems and genetically engineered mouse models to identify and characterize the genes/signaling pathways that are determinants of susceptibility to skin cancer caused by solar UVB radiation. We are interested the roles of the basic leucine zipper transcription factors, CCAAT/enhancer binding proteins (C/EBPs) and long noncoding RNA, in the UVB-induced DNA damage response involving cell cycle arrest and apoptosis, the maintenance of genomic integrity as well as delineation of the mechanisms of their oncogenic and tumor suppressor functions.
The research in the Epidemiology and Environmental Epigenomics lab (Hoyo, Jirtle and Skaar) involves the identification and characterization of epigenomic marks that that are perturbed by early environmental exposures to alter susceptibility to chronic diseases, including cancer, later in life. We use cohort study design in early life to characterize the timing of exposures, and the stability of epigenetic response over time. We also use case-control designs, to determine the extent to which identified epigenetic marks are associated with chronic diseases. Long term, these epigenetic marks should be developed as assessment biomarkers and to generate hypothesis relating their involvement in the etiology of specific disease pathways.
My research is focused on analytics at the intersection of human health and large, complex sets of data. I conduct Bioinformatics analysis and research in support of projects across the members of Center of Human Health and the Environment (CHHE) and Bioinformatics Research Center (BRC) as a collaboration. I perform consultation at the design stage of research studies to insure that the experimental design of the studies are valid, efficient, and correctly powered. My expertise includes a broader ranges such as cancer genomics, immunology, infectious diseases, epidemiology and application development; and domain expertise includes proteomics, metabolomics, genomics, personalized medicine, and biosignature discovery. I have worked with collaborators on discoveries relating to cancer, infectious disease, immunology, environmental exposure and application development. I have analytical capabilities of whole genome/exome sequencing, RNA-Seq, ChIP-Seq, FAIRE-Seq, small/long ncRNA transcriptome, microbiome, and expression/genotype microarrays.
My research interests are in epigenetics, genomic imprinting, and the fetal origins of disease susceptibility. My lab identified the first imprinted tumor suppressor gene, IGF2R, and showed that its inactivation increases tumor resistance to radiotherapy. We discovered a novel imprinted domain at human 14q32, and identified the Callipyge or ‘beautiful buttocks’ locus in the homologous region of sheep. The lab subsequently traced the mammalian origin of genomic imprinting from monotremes to placental mammals. These studies provided the crucial data that allowed my lab to complete the first genome-wide mapping of human imprinted genes using a bioinformatic approach
My research aims at developing cutting-edge imaging and force techniques for investigating biomolecules to answer critical biological questions. I have through my research contributed to a diverse range of topics including DNA structure, protein-DNA interactions, epigenetic regulation, and live cell imaging. The main focus of my current research is to elucidate the molecular mechanism underlying the replication of the mitochondrial DNA and telomere maintenance pathways at the single-molecule level and studying how the defects in mitochondrial replication machinery contribute towards various diseases. The grand challenge in the AFM research field is to differentiate biological molecules in AFM images. To meet this challenge, I addressed the drawbacks of recognition AFM imaging and force spectroscopy by simultaneously imaging the topography and the functionality using cantilevers modified with antibodies. More recently, we have developed the DREEM imaging technique in collaboration with the Erie group at UNC-Chapel Hill, which is capable of detecting the paths of both ds- and ss-DNA in protein-DNA complexes. I am currently managing multidisciplinary projects through collaborations as well individually pertaining to studying genome and mitochondrial maintenance pathways at the single-molecule level.
My lab is a synthetic biology group that harnesses the information-rich epigenome to understand disease biology and to enable broader biotechnological & cellular engineering applications. We work across multiple biological systems from in vitro systems & yeast, to human stem cells & organoids.
The Kullman laboratory is particularly interested in neural and endocrine pathways that govern critical steps of embryonic development. Much of our work is focused on the role of nuclear receptors and ligand activated transcription factors that regulate key organizational pathways during embryogenesis. A major emphasis of the Kullman laboratory is the application of small aquarium fish models (zebrafish, medaka ) to establish developmental bases of adult disease. Overall, the laboratory is geared towards facilitating a mechanistic understanding of the relationship between chemical-receptor interactions, resultant pleotropic effects and onset and progression of disease etiology.
Dr. Kumar brings expertise in cancer cell and molecular biology, specifically characterizing miRNAs as therapeutic targets and biomarkers for diagnosis, prognosis, and stratification. His lab currently focuses on (1) characterizing molecular targets in prostate, breast, and colon cancer; (2) microRNAs as biomarkers and therapeutic targets in prostate and breast cancer; (3) characterizing molecular targets and signaling pathways modulated by micronutrients; and most importantly, (4) enhancing minority participation in cancer research through education and training in cancer research at all levels.
Rebecca joined the Cowley Lab at NC State in 2021 as a postdoc. She is currently working on two projects: 1) the effects of maternal metabolic state in early development on gene imprinting and programming of liver disease, and 2) how cadmium exposure perturbs nervous system patterning during development.
Shuang Fang Lim serves as a Assistant Professor for the Dept. of Physics. Lim’s research is centered on the synthesis, characterization, photophysics, bioconjugation, and application of UCNPs. These UCNPs are developed for applications as biosensors in microarrays and as biotherapeutics in photodynamic and photothermal therapy. She also works on single molecule epigenetic mapping of DNA and chromatin.
My research is focused on viral immunity and the interferon response in the skin, with particular interest in papillomavirus infections. I am interested in learning the different innate immune pathways involved in viral recognition in canine keratinocytes, the target cell for papillomavirus infections, and the mechanisms behind how papillomaviruses can dampen the immune response to escape detection.
I am a community engagement practitioner with the Community Engagement Cores for CHHE and the Center for Environmental and Health Effects of PFAS. I am currently completing my doctoral work in Science Education, focusing on informal and nonformal learning interventions related to environmental health literacy (EHL). My research interests include EHL, public perceptions of environmental health, program evaluation, and effective science communication strategies.
Inflammation is the first line of defense system, which protects humans from variety of exogenous insults including environmental stressors. However, excess or sustained exposure to stressors induces unregulated inflammation and cell death, which are the major mechanisms by which environmental stressors cause diseases such as chronic inflammatory diseases and cancers. Our research focuses on the intracellular signal transduction pathway that is commonly activated by many types of environmental stressors and leads to inflammation and cell death depending on cellular contexts. Our goal is to understand how stressor-induced inflammation and cell death are regulated at molecular levels.
The overarching strategy of my research program is to inventively fill gaps in biological knowledge by drawing on unexpected tools in the existing diversity of life. I love the pursuit of linking differences in complex traits to specific evolved genetic changes. My ultimate goal is to produce new knowledge with dual impact – informing both our understanding of how genes and species evolve, and providing basic biology insights that may improve the human condition.
Our interests are to determine how environmental exposures affect human health through epigenetic modifications, including DNA methylation and histone modifications that can alter gene expression, affecting cellular differential and development. We are interested in both short-term effects, related to acute toxicity, and long-term effects, that can have outcomes years after exposure, including epigenetic modifications heritable across generations. The plasticity of the epigenome provides both a target susceptible to insult, and a possibility for disease prevention, by protection from epigenetic alterations, and intervention by reversal of alterations. By determining epigenetic markers and mechanisms for the effects of environmental exposures, tools for determining risks of exposure, means of treatment, and assessment of intervention efficacy.
The research in the Smart Lab involves the identification and characterization of genes/signaling pathways that are determinants of susceptibility to cancer, particularly as it relates to gene-environment interactions. We utilize genetic/molecular/cellular-based systems and powerful genetically engineered mouse models to define mechanisms by which environmental stressors induce cancer. We are especially interested in how cells respond to DNA damage to maintain genomic integrity and the role of the basic leucine zipper transcription factors, CCAAT/enhancer binding proteins (C/EBPs) and long noncoding RNAs in this process.
The core research project is to understand the molecular regulatory mechanism of antioxidant detoxification genes, in particular the human ferritin gene that encodes the major cytoplasmic iron storage protein, under the exposure of environmental chemicals and toxicants such as arsenic. Through our ferritin study, we are also interested in the regulation of iron metabolism in normal and disease conditions. Our ongoing projects are branches and new avenues from the core research projects, including microRNA and gene regulation, histone modifications and gene transcription, the Nrf2-ARE signaling pathway, the novel HIPK-CREB/ATF1 signaling pathway under genotoxic and oxidative stress, and the p66Shc longevity gene and mitochondrial oxidative stress and neurodegeneration.
My research interests combine the fields of statistics and genetics and I focus on developing statistical methods that can facilitate genetic epidemiologic research on human complex diseases. Some of my current research projects include statistical modeling of marker-set and gene-set association analysis for diseases and pharmacogenetics, CNV analysis, integrative analysis of multi-omic data, network-guided inference on global and local variant identification in genomic studies.
Research in the Van Dross laboratory is focused on understanding how tumor cells regulate the activity of immune cells. We are particularly interested in examining tumor-immune cell interactions in cancers caused by environmental carcinogens. Our objective is to identify and characterize genes and signaling pathways that are modified by environmental stressors. Current research is examining how COX-2 and its prostaglandin products modulate immunological responses in tumors and dictate tumor cell fate. To investigate this topic, we employ techniques in molecular biology, immunology, photobiology, oncology, and pharmacology using cultured cells, rodent tumor models, and patient tumor samples. Our ultimate goal is to use the information learned from these studies to develop novel chemotherapeutic agents that improve human health.
A main focus of the Wang laboratory in the Physics Department is to use a broad range of biochemical and biophysical assays, including single-molecule atomic force microscopy (AFM) and fluorescence imaging, to study the structure and dynamics of proteins involved in telomere maintenance and DNA repair. The cutting-edge new techniques that we developed during these studies, including a unique DNA stretching method for single-molecule fluorescence imaging and quantum dot labeling of proteins, have uncovered how nucleotide excision repair proteins scan DNA for damage and different DNA damage search modes used by these proteins. Currently, we are especially interested in how DNA lesions affect the DNA binding dynamics of telomere binding proteins and the interplay between telomere binding proteins and DNA repair proteins.
The Wright group develops methods for the analysis and interpretation of genetic data, including the analysis of genome-wide association, gene expression variation, and toxicogenomics. Data from collaborators and public sources is used to inspire novel statistical methods for biological discovery. The biological problems range from assessing gene-environment interactions in disease to dissecting the heritable variation in susceptibility to environmental chemicals.
Three goals of our laboratory are to 1) evaluate how exposure to environmental agents influences immune function, 2) identify novel genetic mediators of innate immunity and 3) develop models for the evolution of innate immune receptors. Nearly all of our research begins with the experimentally amenable zebrafish as a model vertebrate species with the goal of better understanding human immune function and the evolution of immune genes.
Yi-Hui Zhou was appointed in July 2018 as a Chancellor’s Faculty Excellence Program connective cluster member in High-Dimensional Integration of Biological Systems. Zhou is an associate professor in the Department of Biological Sciences and part of the Bioinformatics Research Center. Her research interests include statistical genetics, generalized linear models, and next generation and third generation sequencing models.