BBSP Faculty

We have several areas of research interest broadly in the area of immunomodulation using micro/nanoparticles and other carrier systems.  This can include development of traditional vaccines, therapeutic autoimmune vaccines and classic drug delivery platforms targeted to bacterial, viral or parasitic host cells.  To this end, we also seek to develop new materials and platforms optimal for use in modulating immune responses as well as developing scalable production of micro/nanoparticles.

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.

The UNC Food Allergy Institute (UNCFAI) was established in 2012 to address the growing needs of children and adults with food allergy. Program investigators study the biologic basis of food allergy in the laboratory and in clinical research studies seeking to better understand the role of allergen-specific IgE and the mechanism of allergen immunotherapy. The Institute provides comprehensive, family-centered patient care for food allergy, food-related anaphylaxis, and other related disorders like atopic dermatitis and eosinophilic esophagitis.

The immune system of severely burned patients becomes extremely suppressed after injury. An overwhelming number of patients die from wound infection and sepsis. However, we are unable to graft these patients with skin from other donors as their immune system is still able to reject the graft efficiently. Our inability to cover the wound site leaves the patients further open to bacterial and fungal infections. Our laboratory investigates the translational immune mechanisms for these devastating consequences of burn within mouse models and burn patients. Focuses in the lab include 1) investigation of innate molecule control of both the innate and adaptive immune systems after burn injury, 2) Role of innate signaling to Damage Associated Molecular Patterns in Immune Dysfunction after burn / inhalational injury,focusing on mTOR-mediated Immunomodulation 3) Using NRF2/KEAP1-Targeted Therapy to Prevent Pneumonitis and Immune Dysfunction After Radiation or Combined Burn-Radiation Injury and 4) Investigating sex-specific disparities in Immune Dysfunction after trauma / transplantation. ​

Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.

The Chung lab is engineering immune cells, particularly T cells, to achieve maximum therapeutic efficacy at the right place and timing. We explore the crossroads of synthetic biology, immunology, and cancer biology. Particularly, we are employing protein engineering, next-gen sequencing, CRISPR screening, and bioinformatics to achieve our objectives:

(1) Combinatorial recipes of transcription factors for T cell programming.

(2) Technologies for temporal regulation and/or rewiring of tumor and immune signal activation (chemokine, nuclear, inhibitor receptors).

(3) Synthetic oncolytic virus for engineering tumor-T cell crosstalk.

The overriding goal of Dr. Coleman’s work is to identify novel treatments for alcohol use disorders (AUD) and associated peripheral disease pathologies. Currently, this includes: the role of neuroimmune Signaling in AUD pathology, the role of alcohol-associated immune dysfunction in associated disease states, and novel molecular and subcellular mediators of immune dysfunction such as extracellular vesicles, and regenerative medicine approaches such as microglial repopulation.

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.

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.

We study host defense mechanisms in the lungs, particularly the inflammatory and innate immune processes important in the pathogenesis and course of bacterial pneumonia, acute lung injury/acute respiratory distress syndrome, and cigarette smoke-associated lung disease. Basic and translational studies address mechanisms of host defense, including recruitment and function of leukocytes, vascular permeability leading to edema, bacterial clearance and resolution.  Cell signaling pathways initiated by binding of leukocyte-endothelial cell adhesion molecules and molecular mechanisms underlying the functions of neutrophils are two particular areas.

The overall focus of the laboratory is to develop immunotherapy strategies to treat human malignancies. Specifically, one area of research is dedicated to the genetic engineering of immune cells to redirect their specificity to tumor-associated antigens. The most effective strategies developed in the laboratory are then translated into phase I clinical studies since we have access to the cellular therapeutic facility at UNC. The second area of research is dedicated to the tumor microenvironment and the development of engineering strategies aimed at countering its immunosuppressive properties.

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.

Our research interests focus on the immunologic and genetic mechanisms of lymphomagenesis, particularly in the setting of HIV infection. While hematologic malignancies and lymphoproliferative disorders in sub-Saharan Africa (SSA) arise under intrinsic and extrinsic pressures very different from those in the United States, comprehensive analyses of these diseases have not been performed. We use advanced sequencing, immunophenotypic and cellular analyses to address gaps in our understanding of lymphomagenesis and tumor microenvironment in the context of HIV-associated immune dysregulation, with the goal of translation to clinical care and future clinical trials.

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 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.

The Furey Lab is interested in understanding gene regulation processes in specific cell types, especially with respect to complex phenotypes, and the effect of genetic and environmental variation on gene regulation. We have explored these computationally by concentrating on the analysis of genome-wide open chromatin data generated from high-throughput sequencing experiments; and the development of statistical methods and computational tools to investigate underlying genetic and biological mechanisms of complex phenotypes. Our current projects include determining the molecular effects of exposure to ozone on chromatin, gene regulation, and gene expression in alveolar (lung) macrophages of genetically diverse mouse strains. We are also exploring genetics, chromatin, transcriptional, and microbial changes in inflammatory bowel diseases to identify biomarkers of disease onset, severity, and progression.

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

Fundamentally, our research is focused on how the nervous and immune systems are developmentally educated by infectious and non-infectious stressors across the “gum-to-gut” axis. One current major focus of the lab is to elucidate how early life stress impacts the developing gut and dentition using zebrafish as an ideal — and translational — model organism. We utilize a combination of advanced imaging, next-generation sequencing, and genetic approaches to achieve a greater understanding of how early life events dictate health outcomes across the lifespan and generations. In addition to these primary research interests, we maintain active collaborations with other groups within the Adams School of Dentistry and across campus.

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.

Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.

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.

My research interests and diagnostic responsibilities center around nephropathology and immunopathology. My laboratory carries out basic, translational and clinicopathologic research on kidney diseases. I am most interested in pathogenic mechanisms and pathologic manifestations of glomerular diseases and vasculitis. A major current research focus is on elucidating the pathogenesis of vascular inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCA).

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.

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.

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

Psychoneuroimmunology; the effects of conditioning on lymphocyte reactivity

The Miller lab is working to improve the efficacy of immunotherapy to treat cancer. We aim to develop personalized immunotherapy approaches based on a patient’s unique cancer mutations. We have a particular interest in myeloid cells, a poorly understood group of innate immune cells that regulate nearly all aspects of the immune response. Using patient samples, mouse models, single-cell profiling, and functional genomics approaches, we are working to identify novel myeloid-directed therapies that allow us to overcome resistance and successfully treat more patients.

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.

Our research interests focus on investigating the reparative processes critical to the resolution of acute lung injury. Acute events such as pneumonia, inhalational injury, trauma, or sepsis often damage the lung, impeding its primary function, gas exchange. The clinical syndrome these events can lead to is termed Acute Respiratory Distress Syndrome (ARDS). ARDS is a common pulmonary disease often seen and treated in intensive care units. Despite decades of research into the pathogenesis underlying the development of ARDS, mortality remains high. Our laboratory has built upon exciting observations by our group and others on the importance of how the lung repairs after injury. One type of white blood cell, the Foxp3+ regulatory T cell (Treg), appears essential in resolving ARDS in experimental models of lung injury–through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. Importantly, Tregs are present in patients with ARDS, and our lab has found that subsets of Tregs may play a role in recovery from ARDS.

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.

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.

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 Nguyen lab develops the next generation of effective and safe biotherapeutics for life-threatening diseases such as cancer and myocardial infarction. We engineer novel immunomodulatory carriers based on genetically encoded materials and lipids that home to the site of disease, respond to changes in the microenvironment, and effectively deliver nucleic acids and drugs.

Our lab is broadly interested in utilizing high resolution 3D printing to develop novel drug delivery carriers for the treatment of cancer and infectious diseases. Current research interests lay in manufacturing biodegradable porous hydrogel scaffold implants for cell/drug delivery for the treatment of recurrent brain cancer. We are actively investigating biomaterial properties for passive cell/drug loading into scaffolds as well as developing materials and methods to support conjugation strategies for actuated release mechanisms.

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.

Many diseases of the kidney remain poorly understood. My research program spans a range of disciplines (e.g., genetics, cell biology, immunology) and experimental approaches (e.g., microscopy, molecular biology, biochemistry, and model organisms—Drosophila and zebrafish) to answer fundamental questions regarding the genetic and cellular basis of kidney function and disease. We are also developing novel assays to study autoimmune diseases of the kidney, with the goal of facilitating patient diagnosis and treatment. By applying modern tools to long-standing problems, we hope to translate our research findings to improved patient outcomes.

The goal of my research is to define molecular mechanisms of immune cell co-option by cancer cells, with the hope of identifying novel targets for immune cell reprogramming. Central to our approach is analysis immune cell subtypes in KRas-driven models of pancreatic cancer. We use cell and animals models to study signals important for pro-tumorigenic activity of immune cells, as well as define role of physiologically relevant oncogenic mutations in driving these signals and enabling immune escape.

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.

I work on predicting the determinants of adaptive immune responses. Most of my work has focused on T-cell epitope prediction for mutant antigens derived from cancer. I have collaborated closely with clinical groups to translate this work in personalized cancer vaccine trials. More recently I have also been working on joint T-cell and B-cell prediction for viral pathogens. The technologies and techniques applied across all of my projects are at the intersection of computational immunology, genomics, and machine learning.

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.

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.

My research interests are in the immunology and pathogenesis of Epstein-Barr virus (EBV) associated lymphomas developing in immunosuppressed patients. I have studied the use of EBV specific cytotoxic T-cells (CTLs) for therapy of post-transplant EBV-associated lymphoproliferative disease (PTLD). I am also interested in the preclinical development of cancer immunotherapy approaches for hematological and solid tumors, specifically by using T cells as platform for exploring genetic immune-manipulations to redirect them to tumors by transgenic expression of alpha-betaTCRs or of chimeric antigen/tumor-specific receptors (CARs). My research also focus on gene modifications aimed at improving the homing of T cells to tumor cells , improving their proliferation and persistence and finally overcoming  the inhibitory effect of the tumor environments, including effects of regulatory T (Treg) cells.

The Serody laboratory focuses on tumor and transplant immunology studies using both animal models and translational work with clinical samples. We have performed pioneering work in both of these areas. Our laboratory was the first to describe a role for migratory proteins in the biology of acute GVHD. We were the first group to use eGFP transgenic mice generated in part by our group to track the migration of donor cells after transplant. This work showed a critical role for lymphoid tissue in the activation of donor T cells. Most recently we have been the first group to demonstrate the absence of ILC2 cells in the GI tract after all types of transplant and we have generated novel studies into the ILC2 niche in the bone marrow. For our tumor work we were one of the first groups to use genomic evaluations of the tumor microenvironment to characterize the immune response in cancer models. We were the first group to demonstrate how to enhance checkpoint inhibitor therapy in triple negative breast cancer models and have been one of the leading groups in performing genomic evaluations using TCGA data. Finally, we are one of the leading groups in the world characterizing the role of B cells in the anti-tumor immune response.

The Shaikh lab aims to understand how differing dietary fatty acids regulate outcomes associated with immunity and metabolism in the context of obesity, type 2 diabetes, and cardiovascular diseases. The lab conducts studies at the human level and in mouse models.  We are currently focused on the mechanisms by which omega-3 fatty acids improve chronic inflammation and humoral immunity upon viral infection in obesity. We are also elucidating how select fatty acids disrupt the biophysical organization of the inner mitochondrial membrane of differing cell types and thereby respiratory activity.

We seek to understand how information is encoded and dynamically utilized in immune cells from healthy and disease prone intestines (The Inflammatory Bowel Diseases: Crohn’s disease and Ulcerative Colitis). Our lab is multi-disciplinary and combines high-throughput genomics with innate immunity and microbiology. We focus specifically on genes that regulate response to the bacteria that normally reside in our intestines. Many of these genes make products that regulate the immune system in the intestine. These products defend the intestine against the attack of foreign materials; such as bacteria that live in the intestine. We use genome-sequencing technology to precisely identify regions throughout the genome that are potential ‘on’ or ‘off’ switches for these genes. There is a fine balance between the genes that produce inflammatory substances that are necessary to kill bacteria and genes that produce anti-inflammatory substances that are important to prevent damage to the intestine. If this balance between inflammatory and anti-inflammatory substance production in the intestine is disrupted, IBD may result. Our lab focuses on understanding how these important controllers of inflammation are turned on and off in IBD. We also study how inflammatory and anti-inflammatory signals impact disease severity, progression and response to therapy in individuals with IBD. This information has the potential to increase our understanding of causes of IBD (personalized medicine) and to contribute to the development of new treatments.

The Shiau Lab is integrating in vivo imaging, genetics, genome editing, functional genomics, bioinformatics, and cell biology to uncover and understand innate immune functions in development and disease. From single genes to individual cells to whole organism, we are using the vertebrate zebrafish model to reveal and connect mechanisms at multiple scales. Of particular interest are 1) the genetic regulation of macrophage activation to prevent inappropriate inflammatory and autoimmune conditions, and 2) how different tissue-resident macrophages impact vertebrate development and homeostasis particularly in the brain and gut, such as the role of microglia in brain development and animal behavior.

We are a computational biology lab jointly located between the department of computer science and the computational medicine program. We develop new methods for automated, efficient, and unbiased analysis of immune profiling data, such as, flow cytometry, mass cytometry, and imaging mass cytometry. Our work specifically seeks to link particular immune cell-types and their functional responses to clinical or experimental phenotypes. Application areas of interest include, vaccine development, T-cell differentiation and designing more effective immunotherapies, neurodegenerative diseases, sexually transmitted diseases, and pregnancy. To design scalable and automated tools for these data, we develop and apply new methods using machine learning and graph signal processing.

The Thaxton laboratory studies the intersection of stress and metabolism in immune cells for applications in cancer immunotherapy. Our pursuits center around the biology of the endoplasmic reticulum (ER). We aim to define how stress on the ER defines changes in protein homeostasis, metabolic fate, and antitumor efficacy of immune subsets in human tumors. In order to pursue our goals we collaborate vigorously with clinicians, creating a highly translational platform to expand our discoveries. Moreover, we design unique mouse models and use innovate technologies such as metabolic tracing, RNA-sequencing, and spectral flow cytometry to study how the stress of solid tumors impacts immune function. Ultimately, we aim to discover new ways to restore immune function in solid tumors to offer unique therapies for cancer patients.

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.

Projects involve the study of cellular and molecular events involved in autoimmunity, and development and application of genetic vaccines to prevent and treat autoimmunity and cancer.

We aim to dissect the epigenetic and transcriptional mechanisms that shape T cell lineage specification during development in the thymus and in the periphery upon antigen (microbial, viral) encounter. Aberrant expression of transcription and epigenetic factors can result in inflammation, autoimmunity or cancer. We are using gene deficient mouse models, multiparameter Flow Cytometry, molecular biology assays and next generation sequencing technologies to elucidate the regulatory information in cells of interest (transcriptome, epigenome, transcription factor occupancy).

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).

The Vincent laboratory focuses on immunogenomics and systems approaches to understanding tumor immunobiology, with the goal of developing clinically relevant insights and new cancer immunotherapies.  Our mission is to make discoveries that help cancer patients live longer and better lives, focusing on research areas where we feel our work will lead to cures. Our core values are scientific integrity, continual growth, communication, resource stewardship, and mutual respect.

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.

We are a molecular genetics laboratory studying immune functions by using mouse models. The focus of our research is to investigate the molecular mechanisms of immune responses under normal and pathological conditions. Our goal is to find therapies for various human immune disorders, such as autoimmunity (type 1 diabetes and multiple sclerosis), tumor and cancer, and inflammatory diseases (inflammatory bowel disease, asthma and arthritis).

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.