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Research in the Brouwer laboratory is focused on: (1) hepatic transport of xenobiotics, including mechanisms of uptake, translocation, and biliary excretion; (2) development/refinement of in vitro model systems to predict in vivo hepatobiliary disposition, drug interactions, and hepatotoxicity; (3) influence of disease (e.g., NASH, kidney disease) on hepatobiliary drug disposition; and (4) pharmacokinetics.


The long-term goal of my research is to incorporate ‘omic (genomic, epigenomic, proteomic, etc.) measurements into environmental human health hazard identification, prioritization and risk assessment using a quantitative and interpretable biological systems framework. Thus, short-term goals have been to develop the molecular tools to investigate key biological events, and measurable biomarkers linked to those events, related to important disease processes that are impacted by environmental chemical exposures, such as liver and lung toxicity.  We have focused recent efforts on early-in-life genomic and epigenetic alterations and linkages to latent adverse outcome susceptibility due to commons exposures, genetics, and pre-existing conditions. Our laboratory uses cutting edge techniques such as gene editing tools including CRISPR-based methods; next generation nucleic acid-based sequencing to probe the genome and epigenome; advance, high-throughput microscopy; targeted RNA, DNA, and non-coding RNA measurements such as digital drop PCR and Fireplex; and advanced in vitro models.


My lab in the UNC CEMALB uses translational in vitro and clinical in vivo approaches to investigate how inhaled xenobiotics modify respiratory innate immune responses in people with and without existing lung disease. A central component of my research is the integration of biomedical engineering, additive manufacturing, and advanced cell culture methods to evaluate the health effects of new and emerging tobacco products such as e-cigarettes. I believe the best research is achieved through collaboration across disciplines and welcome interested trainees to contact me to learn more about my lab.


The work focuses on how air pollutants affect human health, the role of genetics and epigenetic factors in determining susceptibility and clinical/dietary strategies to mitigate these effects. There is a strong emphasis on translational research projects using a multi-disciplinary approach. Thus, by using human in vivo models (such as clinical studies) we validate in vitro, epidemiology, and animal findings.


Air pollution exposure is associated with increased hospital visits and mortality, and is a major area of research for the United States Environmental Protection Agency.  The primary research interest of my laboratory is the examination of the effects and mechanisms of air pollutants in the environment on normal cardiopulmonary function (cardiac toxicology), particularly in models of cardiovascular disease, using state-of-the-art targeted and high throughput methods. Research findings are often used to inform environmental public health and contribute to the refinement of the US EPA’s National Ambient Air Quality Standards for specific air pollutants set to limit their health impact.


The Reproductive Endocrinology Group in the National Toxicology Program (NTP) Labs, led by Dr. Fenton, focuses on the role of environmental chemicals in breast developmental timing as it relates to puberty, increased susceptibility to form breast tumors, altered lactational ability, and the effects of chemicals on independent breast cancer risk factors such as obesity, breast density and pubertal timing. The projects within the lab often take a systems biology approach to the problem and instead of delving into exact mechanisms of an insult, which is in line with the missions of the NTP. The group also provides expertise in the use of whole mount mammary gland preparations in evaluating early life development of both male and female rat offspring and lifelong effects in female mice.


Ferguson, Kelly
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Publications
PHD PROGRAM
Toxicology

The Perinatal and Early Life Epidemiology Group conducts research on how maternal exposure to chemicals impacts pregnancy and the development of the fetus and child. We also investigate biological mechanisms of action — such as inflammation, oxidative stress, and endocrine disruption — that connect chemical exposures to adverse birth outcomes.


Fry, Rebecca
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Publications
PHD PROGRAM
Toxicology
RESEARCH INTEREST
Genetics, Systems Biology, Toxicology

The lab focuses on understanding how environmental exposures are associated with human disease with a particular focus on genomic and epigenomic perturbations. Using environmental toxicogenomics and systems biology approaches, we aim to identify key molecular pathways that associate environmental exposure with diseases. A current focus in the lab is to study prenatal exposure to various types of metals including arsenic, cadmium, and lead. We aim to understand molecular mechanisms by which such early exposures are associated with long-term health effects in humans. For example, we are examining DNA methylation (epigenetic) profiles in humans exposed to metals during the prenatal period. This research will enable the identification of gene and epigenetic biomarkers of metal exposure. The identified genes can serve as targets for study to unravel potential molecular bases for metal-induced disease. Ultimately, we aim to identify mechanisms of metal -induced disease and the basis for inter-individual disease susceptibility.


Dr M Ian Gilmour is a Principal Investigator at the National Health and Environmental Effects Research Laboratory (NHEERL), U.S Environmental Protection Agency in RTP.    He received an Honors degree in microbiology from the University of Glasgow, and a doctorate in aerosol science and mucosal immunology from the University of Bristol in 1988.  After post-doctoral work at the John Hopkins School of Public Health and the U.S. EPA, he became a Research Associate in the Center for Environmental Medicine at the University of North Carolina. In 1998 he joined the EPA fellowship program and in 2000 became a permanent staff member.  He holds adjunct faculty positions with the UNC School of Public Health and the Curriculum in Toxicology, and at NC State Veterinary School.  He has published over 80 research articles in the field of pulmonary immunobiology where his research focuses on the interaction between air pollutant exposure and the development of infectious and allergic lung disease.


The Neurotoxicology Group examines the role of microglia interactions with neurons and the associated immune-mediated responses in brain development and aging as they relate to the initiation of brain damage, the progression of cell death, and subsequent repair/regenerative capabilities.  We have an interest in the neuroimmune response with regards to neurodegenerative diseases such as, Alzheimer’s disease.


Research in my laboratory focuses on the effects of air pollution and other environmental pollutants on the cardiovascular and respiratory systems. We use both traditional as well as novel physiological approaches (radiotelemetry, HF echocardiography, physiological challenge testing) to determine not only the short-term effects of exposure, but also the long-term consequences on health, particularly in the development of chronic diseases (e.g. heart disease). Rodent models are used to study the effects of real-world air pollution concentrations on the central and local neural controls of the cardiovascular and respiratory systems that render a host susceptible to adverse health events. Newer exciting research is focused on public health aspects such as nutrition (e.g. vitamin deficiencies) and non-environmental stressors (e.g. noise, climate change, social disruption) as modifiers of air pollution health effects. These studies examine the epigenetic changes that occur in early life or during development that result in physiological effects and future susceptibility.


Research in my lab focuses on the mechanisms by which exposure to air pollutants alters respiratory immune responses and modifies susceptibility to and the severity of respiratory virus infections. Specifically, we are examining the effects of air pollutants such as ozone, woodsmoke and tobacco product exposures on host defense responses and influenza virus infections, using several in vitro models of the respiratory epithelium. In collaboration with physician scientists, we are also translating these studies into humans in vivo.


While both genes and environment are thought to influence human health, most investigations of complex disease only examine one of these risk factors in isolation.  Accounting for both types of risk factors and their complex interactions allows for a more holistic view of complex disease causation.  The Kelada lab is focused on the identification and characterization of these gene-environment interactions in airway diseases, particularly asthma, a disorder of major public health importance.   /  / Additionally, to gain insight into how the airway responds to relevant exposures (e.g., allergens or pathogens), we study gene expression in the lung (particularly airway epithelia). Our goal is identify the genetic determinants of gene expression by measuring gene expression across many individuals (genotypes). / This “systems genetics” approach allows us to identify master regulators of gene expression that may underlie disease susceptibility or represent novel therapeutic targets. /


Our research focuses on understanding mechanisms of cardiovascular and metabolic health effects of inhaled air pollutants. Specific emphasis is given to susceptibility variations due to underlying cardiovascular disease, obesity, and diabetes. The roles of genetic versus physiological factors are examined. We use molecular and high throughput genomics, and proteomics techniques to establish a link with disease phenotype and physiological alterations. State-of-the-art EPA inhalation facilities are used for air pollution exposures in animal models with or without genetic predisposition. The role of environment in disease burden is the focus.


Dr. Edward (Ed) LeCluyse is currently a Senior Research Investigator in the Institute for Chemical Safety Sciences at The Hamner Institutes of Health Sciences.  Dr. LeCluyse leads a program initiative to identify and develop novel in vitro hepatic model systems to examine cellular responses to drugs and environmental chemicals that target known toxicity pathways. The focus of his research efforts has been to create more organotypic, physiologically-relevant in vitro models that integrate the architectural, cellular and hemodynamic complexities of the liver in vivo.


MacDonald, Jeffrey
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Publications
PHD PROGRAM
Toxicology

Dr. Macdonald is the Founder and Scientific Director of the new Metabolomic Facility and Co-Scientific Director of the joint UNC/NCSU/NOAA Marine MRI facility at Pivers Island near Beaufort NC. Dr. Macdonald’s research goal is to combine metabolomics and tissue engineering and apply these tools to quantitative biosystem analysis.


Madden, Michael C.
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Publications
PHD PROGRAM
Toxicology

Exposure to ambient air particulate matter  has been associated with increased human deaths and cardiopulmonary morbidity, such as lung infections and increased asthma symptoms.  I am investigating some types of PM and associated gases  that may be associated with those health effects so  to better regulate or manage the sources of the airborne particles which are identified as playing a role in the adverse health outcomes. I am currently focusing on the effects of diesel exhaust using a variety of approaches ranging from exposing cultured human lung and vascular cells to the exhaust, to studying responses of humans exposed out in traffic.  I am currently designing and implementing testing strategies to assess the toxicity of the future types of vehicular emissions. Additionally some of my research effort attempts to identify what populations are more sensitive to the effects of air pollutants, and the genetic, diet, and environmental reasons behind the increased sensitivity.


Dr. McCullough’s lab takes a translational research approach that incorporates primary cell and organotypic in vitromodels with clinical research (controlled human exposures) to study the role of cellular and molecular mechanisms in mediating the local and systemic effects of exposure to inhaled chemicals.  His laboratory utilizes primary cell/organotypic in vitro models, live cell imaging of fluorescent biosensors, and both traditional and advanced molecular biology/biochemistry methods to characterize the relationship between redox dysfunction/oxidative stress, inflammation, cell signaling pathway activation, epigenetic changes, gene expression, and cell-specific functional outcomes.  In addition to identifying the mechanisms involved in the effects of toxic exposures, Dr. McCullough’s research also aims to identify biomarkers of toxic exposure effects, predicting susceptible populations, and identifying factors that can be used to mitigate adverse exposure outcomes.


Our research focuses on how environmental exposures impact the development of allergic diseases including asthma and food allergy. We are specifically interested in how exposure to environmental pollutants and immunostimulatory molecules (adjuvants) influence allergic sensitization. The goals of our laboratory are to: (1) define the key environmental adjuvants within the indoor exposome that promote allergic sensitization; (2) characterize the molecular mechanisms by which environmental adjuvants and pollutants condition lung antigen presenting cells to induce allergic immune responses; and (3) identify biomarkers of environmental adjuvant exposure that are associated with increased risk for allergic sensitization in children. Through these research endeavors, we hope to identify potential therapeutic targets for environment-mediated allergic diseases, as well as environmental interventions to mitigate the risk for allergic disease development.


Nylander-French, Leena
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Publications
PHD PROGRAM
Toxicology

My research focuses on understanding the relationship between dermal and inhalation exposure and the effect of individual genetic differences on the function of enzymes that detoxify hazardous agents and that affect the development of disease. My research group has pioneered approaches to quantitatively measure skin and inhalation exposures to toxicants; additionally, my group has developed sophisticated exposure modeling tools using mathematical and statistical principles in an effort to standardize and improve exposure and risk assessment.


Peden, David B.
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Publications
RESEARCH INTEREST
Toxicology

Translational and clinical research in environmental lung disease.


My laboratory research is focused on basic cell biology questions as they apply to clinical lung disease problems. Our main work recently has been contributing to the Cystic Fibrosis (CF) Foundtation Stem Cell Consortium, with a focus on developing cell and gene editing therapies for CF. I contribute to UNC team science efforts on cystic fibrosis, aerodigestive cancers, emerging infectious diseases and inhalation toxicology hazards. I direct a highly respected tissue procurement and cell culture Core providing primary human lung cells and other resources locally, nationally and internationally. I co-direct the Respiratory Block in the UNC Translational Educational Curriculum for medical students and also teach in several graduate level courses.


Research in my lab focuses on investigating sex specific effects of air pollutants and new and emerging tobacco products on respiratory immune health. Specifically, the Rebuli lab is examining how the interaction of sex (genetic and hormonal) and toxicant exposure can alter respiratory health. As the majority of research has been historically conducted in men, male animals, or male-derived cell culture models, there is a paucity of information on female respiratory health and sex differences in the effects of toxicant exposure. We are working to fill this knowledge gap by better understanding the role of genetic and hormonal sex on respiratory health. This is particularly important in understanding the development of sex-biased diseases, where men or women are more susceptible to disease development after environmental exposures, such viral infection, asthma, and chronic obstructive pulmonary disease (COPD). We are interested in toxicants such as ozone, wood smoke, cigarette smoke, and e-cigarette aerosols. We investigate effects at both the individual and population level by using clinical (observational clinical studies and prospective exposure trials) and translational (in vitro and ex vivo cell culture) models of the respiratory immune system.


We are interested in unraveling the molecular basis for human disease and discover new treatments focused on human and microbial targets. Our work extends from atomic-level studies using structural biology, through chemical biology efforts to identify new drugs, and into cellular, animal and clinical investigations. While we are currently focused on the gut microbiome, past work has examined how drugs are detected and degraded in humans, proteins designed to protect soldiers from chemical weapons, how antibiotic resistance spreads, and novel approaches to treat bacterial infections. The Redinbo Laboratory actively works to increase equity and inclusion in our lab, in science, and in the world. Our lab is centered around collaboration, open communication, and trust. We welcome and support anyone regardless of race, disability, gender identification, sexual orientation, age, financial background, or religion. We aim to: 1) Provide an inclusive, equitable, and encouraging work environment 2) Actively broaden representation in STEM to correct historical opportunity imbalances 3) Respect and support each individual’s needs, decisions, and career goals 4) Celebrate our differences and use them to discover new ways of thinking and to better our science and our community


Dr. Rizvi’s expertise is in imaging and therapeutic applications of light, bioengineered 3D models and animal models for cancer, and targeted drug delivery for inhibition of molecular survival pathways in tumors. His K99/R00 (NCI) develops photodynamic therapy (PDT)-based combinations against molecular pathways that are altered by fluid stress in ovarian cancer. He has co-authored 46 peer-reviewed publications and 5 book chapters with a focus on PDT, biomedical optics, and molecular targeting in cancer.


Samet, James M.
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Publications
PHD PROGRAM
Toxicology
RESEARCH INTEREST
Immunology, Toxicology

Our laboratory is focused on the cellular and molecular mechanisms that control  inflammatory and adaptive responses induced by inhalation of ambient air pollutants. Projects focus on early events that result in the disregulation of signaling processes that regulate gene expression, specifically oxidative effects that disrupt signaling quiescence in human lung cells. Approaches include live-cell imaging of human lung cells exposed in vitro and ex-vivo and characterization of oxidative protein modifications.


Styblo, Miroslav
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Publications
PHD PROGRAM
Nutrition, Toxicology
RESEARCH INTEREST
Physiology, Toxicology

Dr. Styblo is a biochemist with background in nutritional biochemistry and biochemical toxicology. His research focuses on topics that require expertise in both nutrition and toxicology and typically involve a translational or interdisciplinary approach. His current research projects examine mechanisms and etiology of diseases associated with exposures to environmental toxins with main focus on cancer and diabetes associated with exposure to arsenic (a common drinking water contaminant), and on the role of diet or specific nutrients in prevention of these diseases.


Research in my laboratory focuses on the cardiovascular effects of air pollution and other environmental pollutants in human, animal, and in vitro models, as well as the dietary interventional strategies to mitigate the adverse health effects of air pollution exposure. We are currently conducting two clinical studies to investigate the cardiopulmonary effects of air pollution exposure, and to determine whether dietary omega-3 fatty acids can mitigate the air pollution-induced health effects in human volunteers. These studies provide good training opportunities for students who are interested in training in clinical and translational toxicology research.


The major area of our research is Biomolecular Informatics, which implies understanding relationships between molecular structures (organic or macromolecular) and their properties (activity or function). We are interested in building validated and predictive quantitative models that relate molecular structure and its biological function using statistical and machine learning approaches. We exploit these models to make verifiable predictions about putative function of untested molecules.


Our broad long-term goal is to understand how mammalian cells maintain ordered control of DNA replication during normal passage through an unperturbed cell cycle, and in response to genotoxins (DNA-damaging agents).  DNA synthesis is a fundamental process for normal growth and development and accurate replication of DNA is crucial for maintenance of genomic stability.  Many cancers display defects in regulation of DNA synthesis and it is important to understand the molecular basis for aberrant DNA replication in tumors.  Moreover, since many chemotherapies specifically target cells in S-phase, a more detailed understanding of DNA replication could allow the rational design of novel cancer therapeutics.  Our lab focuses on three main aspects of DNA replication control:  (1) The S-phase checkpoint, (2) Trans-Lesion Synthesis (TLS) and (3) Re-replication.


My research interests are focused on mechanisms associated with altered innate immune functions, which lead to dysregulated adaptive immunity. Currently my research program has three major arms integrated through with a central philosophy. Specifically, our laboratory focuses on the contribution of epithelial cell biology and signaling to innate and adaptive immune homeostasis and dysfunction. We study the contribution of what I term ‘epithelial cell innate immune (dys)function’ to three major disease conditions: pancreatic cancer, type 1 diabetes (autoimmunity), and periodontal disease (autoinflammation). While appearing to be a diverse research program, we have found that many of the mechanisms and systems in play are surprisingly (or maybe not so surprisingly) similar allowing for rapid translation of our findings. Importantly, previous investigations into the role of epithelial cells in immunobiology have been hindered by a lack of robust primary cell culture techniques, which our laboratory has been able to overcome using both animal and human tissues. Thus, using our novel and unique tools we are able to evaluate our findings in the human conditions, again making translation of our findings that much more feasible. In addition to my primary research objectives, my collaborative research programs, have allowed me to be involved, at some level, in investigating the basic biology of health, multiple autoimmune conditions, autoinflammation, sepsis, and exercise induced inflammation I have been blessed with the opportunities to couple my passions and expertise with that of others to bring together multiple research communities with the goal of advancing human health and hope to be able to continue to do so for years to come.


Watkins, Paul
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Publications
PHD PROGRAM
Toxicology
RESEARCH INTEREST
Physiology, Toxicology

Mechanistic toxicology, hepato-toxicology, research translation, biomarkers


Reproductive biology of early mammalian embryogenesis including gametogenesis, fertilization, and preimplantation embryo development. Effects of environmental disrupting chemicals on female reproductive tract development and function, with a focus on epigenetic alterations.