Group leaders: David Aylor, dlaylor@ncsu.edu
Mike Cowley, macowley@ncsu.edu

Who we are: Our interest group includes researchers studying the underpinings of susceptibility. Particular interests are the molecular consequences of early-life toxicant exposures, epigenetic biomarkers that predict disease outcomes, models of epigenetic inheritance, and gene by environment interactions. Our group includes researchers at NC State, ECU, and North Carolina Central University.
Main goal: To share expertise and ideas on experimental designs, technologies, and conceptual frameworks in the areas of environmental epigenetics and genetics.

 

Members

Akpa, Belinda
Assistant Professor, Dept. of Molecular Biomedical Sciences
Email |  Personal website

My group develops mathematical models to connect molecular events to dynamic physiological outcomes. Current areas of interest include: host-pathogen interactions, cardiovascular systems pharmacology, and molecular and systems toxicology.

 

Aylor, David L.
Associate Professor, Dept. of Biological Sciences
Email  |  Personal website

Our lab’s core goal is to identify genetic variants that influence complex traits, genome function, and environmental response. My work has been focused on developing new systems genetics approaches to accomplish that goal. Systems genetics integrates modern high-throughput molecular biology with classical complex trait analysis by considering molecular profiles (such as mRNA abundance) alongside clinical and developmental traits. Current projects in the Aylor lab focus on 1) genetic susceptibility to diethylstilbestrol (DES), a drug that caused infertility and vaginal cancer in some adults who were exposed prenatally; 2) genetic mechanisms of hybrid male sterility in mice; and 3) identifying gene regulatory elements that vary between mouse strains.

 

Breen, Matthew
Oscar J. Fletcher Distinguished Professor, Dept. of Molecular Biomedical Sciences
Email  |  Personal website

Dr. Matthew Breen’s research focuses on genomics, genome mapping and the comparative aspects of canine cancer. In addition his lab is using high throughput molecular cytogenetics for anchoring emerging genome assemblies and for evaluating the changes to genome structure that occur during speciation. The lab is also developing new molecular assays for diagnostic and prognostic use in veterinary medicine.

 

Cowley, Michael A.
Assistant Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Fleming, Jodie M.
Assistant Professor, Dept. of Biology, NCCU
Email  |  Personal website

The overall goal of our lab is to characterize the role of the tissue microenvironment on the behavior and function of normal mammary cells, as well as determine its role in the development and progression of breast cancer. Our program focuses on the early initiating/promoting factors from the microenvironment, including dietary factors and environmental toxins, and how these factors lead to differences in tumor phenotype. Our approach uses both observation and experimental types of data to integrate the burgeoning field of tumor microenvironment with health disparities research.

 

Grant, Delores
Professor, Dept. of Biological and Biomedical Sciences, NCCU
Email  | Personal website

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.

 

Hall, Jonathan
Research Assistant Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Hoyo, Cathrine
Associate Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Jima, Dereje
Research Scholar, Center for Human Health and the Environment
Email  |  Personal website

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.

 

Jirtle, Randy L.
Adjunct Professor, Dept. of Biological Sciences
Email  |  Personal website

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

 

Kaur, Parminder
Research Assistant Professor, Dept of Physics
Email  | Personal website

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.

 

Keene, Keith
Assistant Professor, Dept. of Biology, ECU
Email  |  Personal website

My research focuses on using Genomic approaches to understand complex diseases and health disparities including type 2 diabetes and stroke, particularly in African Americans. Utilizing next generation sequencing, epigenetics, and genome-wide association studies (GWAS), my research aims to identify heritable factors contributing to health disparities. The inclusion of -Omics data will facilitate personalization of risk assessment, prediction of disease (re)occurrence, and targeted prevention (including gene therapy or pharmacogenomic targets). Furthermore, findings may have broader implications by providing insight into environmental exposures (and responses to such exposures), heritable factors that influence the ability to control manageable risk factors, and likewise one’s response to treatments.

 

Kullman, Seth W.
Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Luff, Jennifer
Assistant Professor, Dept. of Population Health and Pathobiology
Email  |  Personal website

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.

 

Mowat, Freya
Assistant Professor, Dept. of Clinical Sciences
Email  |  Personal website

The Mowat lab studies diseases of the light-sensitive retina in the eye. Our current research focuses include 1. The pathogenesis of spontaneous immune-mediated retinal disease in dogs (a disease called sudden acquired retinal degeneration syndrome/SARDS). 2. The effect of oxidative damage on the canine central retina as a method to study the human foveomacular susceptibility to diseases such as age-related macular degeneration 3. We are also studying a suspected X-linked retinal degeneration seen in a population of North Carolina red wolves.

 

Ninomiya-Tsuji, Jun
Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Roberts, Reade
Assistant Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Skaar, David
Research Assistant Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Smart, Robert C.
William Neal Reynolds Distinguished Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Tsuji, Yoshiaki
Professor, Dept. of Biological Sciences
Email  |  Personal website

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.

 

Tzeng, Jung-Ying
Associate Professor, Dept. of Statistics
Email  |  Personal website

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.

 

Wang, Hong
Assistant Professor, Dept. of Physics
Email  |  Personal website

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.

 

Wright, Fred
Professor, Dept. of Statistics
Email  |  Personal website

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.

 

Yoder, Jeffrey A.
Associate Professor, Dept. of  Molecular Biomedical Sciences
Email  |  Personal website

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.