BBSP Faculty

The Arthur lab is interested in mechanisms by which inflammation alters the functional capabilities of the microbiota, with the long-term goal of targeting resident microbes as a preventative and therapeutic strategy to lessen inflammation and reduce the risk of colorectal cancer. We utilize a unique and powerful in vivo system – germ-free and gnotobiotic mice – to causally link specific microbes, microbial genes, and microbial metabolites with health and disease in the gut.  We also employ basic immunology and molecular microbiology techniques as well as next generation sequencing and bioinformatics to evaluate these essential host-microbe interactions.

My research aims to understand the pathogenesis and host immune response to emerging and re-emerging viral infections, including encephalitic alphaviruses such as chikungunya virus and respiratory coronaviruses such as SARS-CoV-2. Other areas of interest include examination of genetic and environmental factors that influence the response to infection and disease outcome, evaluation of vaccines and novel therapeutics against emerging viruses, and development and optimization of animal models of infectious disease.

My laboratory studies the relationship between host nutrition and the immune response to infectious disease. Using a mouse model of obesity, we are exploring the mechanism(s) for high mortality from influenza infection in obese mice compared with lean mice. We also have an ongoing clinical research study designed to understand the mechanism(s) involved that impair the influenza vaccine response in obese adults compared with healthy weight adults. We have also demonstrated that host deficiencies in antioxidant nutrients can lead to viral mutations resulting in an avirulent pathogen becoming virulent, suggesting that the host nutritional status can be a driving force for the evolution of viruses.

We study the molecular mechanisms of HIV latency. Transcriptional silencing of HIV is a key mechanism of persistence in patients, and is a barrier to viral eradication, but little is known about the latent reservoir or the molecular mechanisms that regulate it. As such, our repertoire of drugs for targeting latently infected cells is limited. Some latency reversing agents (LRAs) have been developed, but these are typically reactivate only a minor subset of proviruses. This inefficiency is in part due to the reservoir not constituting a uniform target, but instead being a heterogeneous set of cells with diverse characteristics and restrictions to HIV expression. However, most analyses of latency use bulk cell cultures assays in which crucial information about the behavior of individual cells is lost. Also, latently infected cells in patient samples are exceedingly rare, making them very difficult to study directly. New technological breakthroughs in the field of single cell analysis as well as the development of primary cell models for HIV latency now open the possibility of observing how latently infected cells form and are maintained at single cell resolution. Our lab has developed tools to study the establishment, maintenance and reversal of HIV latency at single cell resolution using multi-omics methods. Furthermore, we combine these approaches with genetic perturbation, time-lapse microscopy and novel bioengineering tools to gain insight into how the host cell regulates HIV latency. We have recently discovered using single cell RNAseq (scRNAseq) that latency in primary CD4 T cells is associated with expression of a distinct transcriptional signature (Bradley et al 2018). Our hypothesis is that this signature represents part of a cellular program that regulates latency, and that this program is an exciting novel target for the development of LRAs. Ongoing projects in the lab involve the application of new technologies to our model systems, and testing/validation of the roles of host cell pathways we have identified in HIV latency. Our overall goal is to identify new targets for the development of drugs to clear the HIV reservoir.

Our laboratory now studies mechanisms of genome replication and pathogenesis of respiratory enteroviruses and evolution of neurovirulence using the tools of mechanistic enzymology, cell biology, stem-cell engineering, and virology. Our laboratory is also pioneering the development of tools to monitor viral infection dynamics on the single-cell level, aka “single-cell virology.”

My lab is focused on the improvement of treatment of chronic bacterial infections. We aim to determine the mechanisms of antibiotic tolerance. Our aim is to understand the physiology of the bacterial cell, primarily Staphylococcus aureus, during infection and how this physiology allows the cell to survive lethal doses of antibiotic. We will use advanced methods such as single cell analysis and Tn-seq to determine the factors that facilitate survival in the antibiotic’s presence. Once we understand this tolerance, we will develop advanced screens to identify novel compounds that can be developed into therapeutics that can kill these drug tolerant “persister” cells and eradicate deep-seated infections.

Dr. Cotter’s research is aimed at understanding molecular mechanisms of bacterial pathogenesis. Using Bordetella species as models, her group is studying the role of virulence gene regulation in respiratory pathogenesis, how virulence factors activate and suppress inflammation in the respiratory tract, and how proteins of the Two Partner Secretion pathway family are secreted to the bacterial surface and into the extracellular environment. A second major project is focused on Burkholderia pseudomallei, an emerging infectious disease and potential biothreat agent. This research is aimed at understanding the role of autotransporter proteins in the ability of this organism to cause disease via the respiratory route.

The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.

We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions. All of our study organisms are sequenced, making the tools of genomics accessible.

Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease. In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.

Our research focuses on the immunological aspects of pathogen-host interactions. The lab is actively involved in HIV pathogenesis and vaccine studies using the nonhuman primate model of SIV infection. We are particularly interested in pediatric HIV transmission by breast-feeding and the early, local host immune response. A main research focus is on developmental differences in host immune responses between infants and adults and how they alter pathogenesis. The effect of co-infections (e.g. malaria and Tb) on HIV pathogenesis and transmission is a second research focus. The lab is developing a nonhuman primate model of SIV-Plasmodium fragile co-infection to study HIV-P. falciparum infection in humans.

We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.

Our lab tries to understand viral pathogenesis. To do so, we work with two very different viruses – West Nile Virus (WNV) and Kaposi¹s sarcoma-associated herpesvirus (KSHV/HHV-8).

My lab studies a recently identified pathogen-sensing signaling complex known as the inflammasome. The inflammasome is responsible for the proteolytic maturation of some cytokines and induces a novel necrotic cell death program. We have found that critical virulence factors from certain pathogens are able to activate NLRP3-mediated signaling, suggesting these pathogens may exploit this host signaling system in order to promote infections.  Our lab has active research projects in several areas relating to inflammasome signaling ranging from understanding basic molecular mechanisms of the pathway to studying the role of the system in animal models of infectious diseases.

The Ehre laboratory studies the role of mucus in obstructive pulmonary diseases, such as asthma, and cystic fibrosis (CF), as well as in response to respiratory viruses (SARS-CoV-2 and RSV). Our research goal is to gain insights into the basic defects of airway mucus that lead to impaired mucociliary clearance and viral penetration. We use in vitro and in vivo models to study disease pathogenesis, test pharmacological agents and investigate how mucus obstruction and viral infection cause epithelial damage. In addition, we examine patient specimens to understand the role of inflammatory cytokines in disease severity. For these projects, we use integrative omics technologies (transcriptomics, digital spatial profiler, phenocycler) and high-resolution imaging (live, laser and scanning/transmission electron microscopy) to answer critical questions regarding mucus biology and airways response to inhaled pathogens and/or treatment.

In the Ferris lab, we use genetically diverse mouse strains to better understand the role of genetic variation in immune responses to a variety of insults. We then study these variants mechanistically. We also develop genetic and genomic datasets and resources to better identify genetic features associated with these immunological differences.

Fessler laboratory investigates mechanisms of the innate immune response, in particular Toll like Receptor (TLR) pathways and how they regulate inflammatory and host defense responses in the lung.  To this end, we use both in vitro (macrophage cultures) and in vivo (mouse models of acute lung injury and pneumonia) model systems, and also use translational approaches (e.g., studies using human peripheral blood leukocytes and alveolar macrophages).  An area of particular interest within the laboratory is defining how cholesterol trafficking and dyslipidemia innate immunity.

Our lab studies the underlying structural and functional substrates of behavior in disease using rodent models. Specifically our goal is to develop a better understanding of how cellular function in the CNS is affected by drug-related substances (opioids, cannabinoids) in the context of HIV infection. That includes the study of how drugs of abuse exacerbate the pathogenesis of neuroAIDS but also the study of targets within the endocannabinoid system for the potential treatment of HIV. We use various in vivo and in vitro techniques, including primary cell culture models, behavioral conditioning tasks, live cell imaging, and electrophysiology.

Our laboratory studies the role of the blood coagulation system in inflammatory, infectious, and malignant disease. Specifically, we are interested in better defining the roles of factors such as prothrombin, fibrinogen and plasminogen in driving disease processes in the contexts of pancreatic ductal adenocarcinoma (PDAC), Staphylococcus aureus infection, and obesity/metabolic syndrome. Current studies suggest that coagulation factors drive mechanisms of disease both dependent and independent of their traditional roles in hemostasis and thrombosis. Our overall goal is to translate this knowledge into novel approaches for treating these common yet deadly diseases.

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 Good Laboratory is focused on the cellular and molecular mechanisms involved in the pathogenesis of a devastating intestinal disease primarily affecting premature infants called necrotizing enterocolitis (NEC). The long-term goal of the Good Lab is to understand the signaling pathways regulating the uncontrolled immune response in NEC and how these responses can be prevented through dietary modifications or targeted intestinal epithelial therapies. Her basic and translational research utilizes a bench-to-bedside approach with multiple cutting-edge techniques. In her pre-clinical studies, their team utilizes a humanized neonatal mouse model of NEC to understand the signaling pathways and immune cell responses involved in NEC development. Specifically, the laboratory interrogates ways to modulate the immune response, epithelial cell and stem cell regeneration as well as early microbial colonization during NEC. In the clinical component of her research program, Dr. Good leads a large multi-center NEC biorepository for the dedicated pursuit of molecular indicators of disease and to gain greater pathophysiologic insights during NEC in humans. Dr. Good also developed a premature infant intestine-on-a-chip model to study NEC and provide a personalized medicine approach to test new therapeutics. Her laboratory is currently funded with multiple NIH R01 grants and has previously received K08 and R03 funding as well as awards from the March of Dimes, the Gerber Foundation and the NEC Society.

We are a human immunology lab focusing on all aspects of T cell immunobiology in HIV-1 infection. Studies range from basic questions like, ‘What are the determinants of the first T cell response following infection?’ to translational challenges such as ‘What is the best design for a T cell vaccine to either prevent infection or achieve HIV-1 cure?’

Keywords: T cells, HIV-1, Escape, CD8 T cells, Vaccines, Cure, Vaccines

We study alphavirus infection to model virus-induced disease.  Projects include 1) mapping viral determinants involved in encephalitis, and 2) using a mouse model of virus-induced arthritis to identify viral and host factors associated with disease.

Individuals with alpha-gal syndrome, characterized by delayed anaphylaxis (severe allergic reactions) to mammalian meat, have been reported across the globe, yet we have limited understanding of the mechanisms underlying this condition. My lab explores the role of glycolipids interacting with different cells within our innate and adaptive immune systems in the pathogenesis of this allergy. Our vision is to broaden understanding of glycolipids and their role in hypersensitivity disorders. We also want to understand why tick exposure, which is associated with the development of alpha-gal meat allergy, can promote allergic immune responses and how epigenetic dysregulation may influence allergic immune responses. PhD Program: Pathobiology and Translational Science.

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.

Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention.

Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.

We use studies of HIV/SIV evolution to reveal information about viral dynamics in vivo. This typically involves genetic and/or phenotypic analyses of viral populations in samples from HIV-infected humans or SIV-infected nonhuman primates (NHPs). We are currently exploring the mechanisms that contribute to neurocognitive impairment in HIV-infected people by sequencing viral populations in the CNS of humans and NHPs not on antiretroviral therapy. We are also using these approaches to examine viral populations that persist during long-term antiretroviral therapy in an effort to better understand the viral reservoirs that must be targeted in order to cure HIV-infected people.

Our dynamic group are broadly involve in three topics: (i) prevention of infectious diseases by harnessing interactions between secreted antibodies and mucus, (ii) immune response to biomaterials, and (iii) targeted delivery of nanomedicine.  Our group was the first to discover that secreted antibodies can interact with mucins to trap pathogens in mucus.  We are now harnessing this approach to engineer improved passive and active immuniation (i.e. vaccines) at mucosal surfaces, as well as understand their interplay with the mucosal microbiome.  We are also studying the adaptive immune response to polymers, including anti-PEG antibodies, and how it might impact the efficacy of PEGylated therapeutics.  Lastly, we are engineering fusion proteins that can guide targeted delivery of nanomedicine to heterogenous tumors and enable personalized medicine.

We use molecular virology approaches and mouse models of infection to understand innate immune mechanisms that control arbovirus pathogenesis (e.g. West Nile, Zika, and La Crosse viruses). Bat flaviviruses have unusual vector/host relationships; understanding the viral and host factors that determine flavivirus host range is important for recognizing potential emerging infections. We are studying the antiviral effects of interferon lambda (IFN-λ) at barrier surfaces, including the blood-brain barrier and the skin. We also use mouse models of atopic dermatitis and herpes simplex virus infection to understand the effects of IFN- λ in the skin.

Dr. Lin is an infectious disease physician-scientist whose research lies at the interface of clinical and molecular studies on malaria. My current projects focus on 1) determinants of malaria transmission from human hosts to mosquitos and 2) the epidemiology and relapse patterns of Plasmodium ovale in East Africa. Work in my lab involves applying molecular tools (real-time PCR, amplicon deep sequencing, whole genome sequencing, and to a lesser extent antigen and antibody assays) to samples collected in clinical field studies to learn about malaria epidemiology, transmission, and pathogenesis.

Biochemistry, cell biology, and immunology of skin, immunopathogenesis of autoimmune and inflammatory skin blistering diseases.

Traditionally, basic science has sought to enter the translational pipeline through what can be referred to as “Bottom-Up” science, that is, studies that start with a hypothesis in the lab and aim to develop clinical relevance of the findings. In some cases, notably in conventional antibiotic development, this has worked well – but it assumes one-size fits all solutions that are only as good as our assumptions about the biology of many infectious diseases such as tuberculosis. By contrast, my research focuses on a “Top-Down” approach, leveraging the power of bacterial population genomics to identify bacterial processes important for Mtb success in people and to then employ cutting-edge experimental techniques to mechanistically dissect these processes with the goal of leveraging them using new translational tools.

In my work to date, I have applied this “Top-Down” strategy to define bacterial determinants of treatment outcomes and transmission success, as evident in first-author/corresponding author publications in prestigious journals such as Science, Nature Ecology Evolution, Cell Host Microbe, Science Advances, Genome Biology, PNAS, etc. My work combines expertise in evolutionary biology and bacterial genomics, cutting-edge bacterial genetics and high-throughput experimental phenotyping.

In my own lab, I will use these tools to (1) define the biological mechanisms that enable Mtb to survive antibiotic treatment; (2) identify bacterial determinants of TB transmission success; and (3) elucidate the evolutionary mechanisms underlying the emergence of new bacterial pathogens.

The Livraghi-Butrico lab is focused on exploring the key determinants of effective airway mucus clearance in health, as well as the consequences of its derangement in muco-obstructive lung diseases. Our lab leverages the unparalleled functional integration offered by in vivo animal models to test mechanistic hypotheses and vet therapeutic options for pre-clinical development.

The overall goal of our laboratory is to obtain new insights into the host-virus interaction, particularly in HIV infection, and translate discoveries in molecular biology and virology to the clinic to aid in the treatment of HIV infection. A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. Current work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. These studies give insight into the basic molecular mechanisms of eukaryotic gene expression, as well as new therapeutic approaches for HIV infection.

Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis and the development of therapeutic strategies for the treatment of neuroinflammation. Inflammatory changes within the brain caused by the viral infection initiate a toxic cascade that disrupts normal neural function and can eventually lead to neuronal death. To explore the mechanisms responsible for this damage, we investigate changes in calcium homeostasis, glutamate receptor function and inflammatory responses in primary neuronal, microglial and macrophage cultures. New therapeutic approaches targeted to signal transduction pathways and calcium regulation that protect the neurons and reduce inflammation are under investigation.

Molecular genetic analysis of virulence of Yersinia and Klebsiella: My laboratory uses Yersinia enterocolitica, Y. pestis, and Klebsiella as model systems to study bacterial pathogenesis. The long-term goals of our work are to understand the bacteria-host interaction at the molecular level to learn how this interaction affects the pathogenesis of infections and to understand how these pathogens co-ordinate the expression of virulence determinants during an infection. To do this we use genetic, molecular and immunological approaches in conjunction with the mouse model of infection.

The overall focus of our lab is to develop new and exciting approaches for enhancing the efficacy of cancer immunotherapies. We utilize cutting-edge techniques to identify transcriptional and epigenetic regulators controlling T cell differentiation and function in the tumor microenvironment, and we seek to leverage this insight to reprogram or tailor the activity of T cells in cancer. Our group is also interested in understanding how to harness or manipulate T cell function to improve vaccines and immunotherapies for acute and chronic infections.

My work focuses on the role of plant pathogens in (A) controlling or facilitating biological invasions by plants, (B) structuring plant communities, and (C) modulating the effects of global change on terrestrial ecosystems.  My group works on viruses, bacteria, and fungi that infect wild plants, chiefly grasses and other herbaceous species. Ultimately, I am interested in the implications of these processes for the sustainable provisioning of ecosystem services and for the conservation of biological diversity.

Our lab focuses on the life cycle of cancer-associated human papillomaviruses (HPV); small DNA viruses that exhibit a strict tropism for the epithelium. Several studies in our lab focus on the interface of HPV with cellular DNA damage response (DDR) pathways and how HPV manipulates DNA repair pathways to facilitate viral replication. We are also interested in understanding how the viral life cycle is epigenetically regulated by the DDR as well as by other chromatin modifiers. Additionally, we are investigating how HPV regulates the innate immune response throughout the viral life cycle.

The main goal of the Nagarajan lab research program focuses on how the innate branch of the immune system regulates adaptive immunity, as it relates to the pathogenesis of autoimmune disease such as lupus or rheumatoid arthritis (RA)-induced cardiovascular disease.   IgG-Fcgamma receptor (FcgR)-mediated signaling is critical for mediating host defense against infectious disease, but they also mediate disease pathology in autoimmunity and atherosclerosis. Specifically, we are studying the role of IgG-Fcgamma receptor (FcgR) signaling network in innate immune cells activation that contributes to autoantibody production and T cell subset activation associated with autoimmune, and cardiovascular diseases.  We are using a repertoire of relevant knockout mouse and humanized FcgR mouse models to address the questions of how FcgR-mediated signaling promotes autoimmune disease-induced atherosclerosis. As a translational component, we are collaborating with rheumatologists and cardiologists to analyze changes in innate and T cell subsets in patients with lupus or RA, who has premature atherosclerosis.

The overall focus of research in my laboratory is to improve the diagnosis and treatment of airway diseases, especially those that result from impaired mucociliary clearance. In particular, our efforts focus on the diseases cystic fibrosis and primary ciliary dyskinesia, two diseases caused by genetic mutations that impair mucociliary clearance and lead to recurrent lung infections. The work in our laboratory ranges from basic studies of ciliated cells and the proteins that make up the complex structure of the motile cilia, to translational studies of new drugs and gene therapy vectors. We use a number of model systems, including traditional and inducible animal models, in vitro culture of differentiated mouse and human airway epithelial cells, and direct studies of human tissues. We also use a wide range of experimental techniques, from studies of RNA expression and proteomics to measuring ciliary activity in cultured cells and whole animals.

My laboratory, located in the Cystic Fibrosis/Pulmonary Research and Treatment Center in the Thurston-Bowles building at UNC, is interested in how respiratory viruses infect the airway epithelium of the conducting airways of the human lung.

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.

Our lab uses a systems biology approach to study phenotypic heterogeneity in bacteria. We develop tools that quantify single cell bacterial transcription. We then compare dynamic measurements during vegetative growth and infection to identify regulators of gene expression and mechanisms that bacteria use to coordinate community organization. With this data we want to understand the role of heterogeneity and noise in infectious disease.

Our long term goals are to better define mechanisms of chronic intestinal inflammation and to identify areas for therapeutic intervention. Research in our laboratories is in the following four general areas: 1) Induction and perpetuation of chronic intestinal and extraintestinal inflammation by resident intestinal bacteria and their cell wall polymers, 2) Mechanisms of genetically determined host susceptibility to bacterial product,. 3) Regulation of immunosuppressive molecules in intestinal epithelial cells and 4) Performing clinical trials of novel therapeutic agents in inflammatory bowel disease patients.

Dr. Sheahan is an expert virologist with a primary appointment in the Department of Epidemiology in the Gillings School of Global Public Health and a secondary appointment in Microbiology and Immunology in the School of Medicine. His research is focused on understanding emerging viral diseases and developing new means to stop them with a current focus on coronavirus and hepacivirus.

First, we study the complex HIV-1 population that exists within a person.  We use this complexity to ask questions about viral evolution, transmission, compartmentalization, and pathogenesis.  Second, we are exploring the impact of drug resistance on viral fitness and identifying new drug targets in the viral protein processing pathway.  Third, we participate in a collaborative effort to develop an HIV-1 vaccine.  Fourth, we are using mutagenesis to determine the role of RNA secondary structure in viral replication.

Our lab studies the mechanisms facultative pathogens use to adapt to disparate and changing extracellular conditions. Our primary interest is in the ability of Vibrio cholerae, the causative agent of cholera, to persist in its native aquatic environment and also flourish in the host intestinal tract. We are addressing key questions about the role of cyclic diguanylate, a signaling molecule unique to and ubiquitous in bacteria, in the physiological adaptations of V. cholerae as it transits from the aquatic environment into a host. In addition, we are identifying and characterizing factors produced by V. cholerae during growth in a biofilm, a determinant of survival in aquatic environments, that contribute to virulence.  I will be accepting rotation students beginning in the winter of 2009.

By 2035, more than 500 million people worldwide will be diagnosed with diabetes. Individuals with diabetes are prone to frequent and invasive infections that commonly manifest as skin and soft tissue infections (SSTIs). Staphylococcus aureus is the most commonly isolated pathogen from diabetic SSTI. S. aureus is a problematic pathogen that is responsible for tens of thousands of invasive infections and deaths annually in the US. Most S. aureus infections manifest as skin and soft tissue infections (SSTIs) that are usually self-resolving. However, in patients with comorbidities, particularly diabetes, S. aureus SSTIs can disseminate resulting in systemic disease including osteomyelitis, endocarditis and sepsis. The goal of my research is to understand the complex interactions between bacterial pathogens and the host innate immune response with focus on S. aureus and invasive infections associated with diabetes. My research is roughly divided into two project areas in order to understand the contributions of the pathogen and the host response to invasive infections associated with diabetes. Project 1: Defining mechanisms of immune suppression in diabetic infections. Project 2: Determine the role of bacterial metabolism in virulence potential and pathogenesis.

I am a clinical/translational researcher in Infectious Diseases. I am the Director of the Immunocompromised Host Program – which provides ID care to patients with transplants, malignancies, and burns. My primary research interests are antibacterial resistance in gram-negative bacilli, and infections in vulnerable patients. I am the PI for the Carbapenem Resistance Consortium for Klebsiella and other Enterobacteriaceae (CRACKLE) and PI for the Multi-Drug Resistant Organism (MDRO) Network. I am also supported by NIAID to evaluate community origins of carbapenem-resistant Enterobacterales.

We are interested in understanding how autoreactive B cells become re-activated to secrete autoantibodies that lead to autoimmune disease.  Our research is focused on understanding how signal transduction through the B cell antigen receptor (BCR) and Toll Like Receptors (TLR) lead to secretion of autoantibodies in Systemic Lupus Erythematosus (SLE).

We want to understand why common pediatric respiratory virus infections cause severe disease in some people. Currently we focus on enterovirus D68, which typically causes colds but rarely causes acute flaccid myelitis, a polio-like paralyzing illness in children. We study both the pathogen and the host immune response, as both can contribute to pathogenesis. Projects focus on use of reverse genetic systems to create reporter viruses to infect both human respiratory epithelial cultures and small animal models such as mice. Human monoclonal antibody effects on pathogenesis are also of interest.

The Whitmire lab investigates how the adaptive immune system protects against virus infection.  The research is focused on understanding the mechanisms by which interferons, cytokines, and other accessory molecules regulate T cell numbers and functions following acute and chronic virus infections.  The goal is to identify and characterize the processes that differentiate memory T cells in vivo. The long-term objective is to develop strategies that improve vaccines against infectious diseases by manipulating these pathways.

We investigate mechanisms in blood coagulation and diseases that intersect with abnormal blood biomarkers and function, including cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism), bleeding (hemophilia), inflammation, obesity, and cancer. We also investigate established drugs and new drugs in preclinical development to understand their role in reducing and preventing disease. Our studies use interdisciplinary techniques, including in vitro, ex vivo, and in vivo mouse models and samples from humans in translational studies that span clinic to bench. Our lab emphasizes a culture of diversity, responsibility, independence and collaboration, and shared excitement for scientific discovery. We are located in the UNC Blood Research Center in the newly-renovated Mary Ellen Jones building.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for a variety of diseases in individuals with compromised immune function. Dr. Wolfgang’s research focuses on the pathogenesis of Pseudomonas aeruginosa infection.  The goal of his research is to understand how this opportunistic pathogen coordinates the expression of virulence factors in response to the host environment. Projects in his laboratory focus on the regulation of intracellular cyclic AMP, a second messenger signaling molecule that regulates P. aeruginosa virulence. Dr. Wolfgang’s laboratory uses a combination of molecular genetics and biochemical approaches to understand how P. aeruginosa controls the synthesis, degradation and transport of cAMP in response to extracellular cues. Other related projects focus on the regulation and function of P. aeruginosa Type IV pili (TFP). TFP are cAMP regulated surface organelles that are critical for bacterial colonization of human mucosal tissue. In addition, the Wolfgang lab is actively involved in characterizing the lung microbiome of patients with chronic airway diseases and studying the interactions between P. aeruginosa and other bacterial species during mixed infections.