Our laboratory studies an amazing regulatory factor known as NF-kappaB. This transcription factor controls key developmental and immunological functions and its dysregulation lies at the heart of virtually all major human diseases.
It has been postulated for some time that cellular transplantation to the liver might allow for the reversal of hepatic based genetic defects or augmentation of hepatocellular function. However, the identification of the proper cell type and transplant conditions to produce liver engraftment and normal hepatocyte function has remained elusive. We have developed an alternative strategy using embryonic stem (ES) cells differentiated /in vitro/ and transplanted into hepatic parenchyma as “gene vectors” in order to restore wild type hepatocellular function.
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.
Steroid hormones regulate tissue-specific gene expression in animals via receptor dependent intracellular signal transduction pathways. We are particularly interested in glucocorticoid receptors and their actions on the immune system because they reflect the primary response to environmental stress. Current research projects are examining the following aspects of glucocorticoid hormone action. A second major interest of the laboratory focuses on evaluating the mechanisms involved in the regulation of apoptosis in normal and neoplastic cells. Research is aimed at the identification and cloning of genes that are responsible for both the initiation and execution of apoptosis.
The major interest of this laboratory is the differentiation and regulation of autoreactive B cells in health and disease. Our long-range goal is to identify and understand the mechanisms that regulate autoreactive B cells and how they fail in disease. Such information is key to devise rational new therapeutic strategies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE). The lab currently has three main research focuses: 1) regulation of B cells specific for the ribonucleoprotein antigen Sm, a target of the immune system in SLE, 2) analysis of how Epstein Barr virus (EBV) contributes to SLE and 3) investigation of activation of anti-Sm B cells in blood of human SLE patients.
We study how Cytotoxic T Lymphocytes (CTL) are activated during infection and cancer. Our long-term goal is to increase immunity in the case of infection or cancer and to decrease immunity in the case of autoimmunity. The approaches that we use include x-ray crystallography and other biophysical techniques such as SPR and ITC, and immunological assays. We are currently working on three systems. 1) basic immunology to understand how cytotoxic T cells are signaled to kill infected or cancer cells. 2) immunotherapy of melanoma using modified T cell receptors. 3) Determining why specific T cells populate pancreatic islets of Langerhans in Type I diabetes. Students working on these projects could work on immunological or biophysical aspects (or both) depending on their interests. Member of the Molecular & Cellular Biophysics Training Program.
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).
The central goal of my research is to understand how immune cells are activated and regulated within the Central Nervous System. Our research looks at the different pathways of activation of the microglia, the role of the microglia in sensory responses, and the role of stress responses in activating and regulating the response of the microglia. We are currently investigating the mechanism of microglia activation and regulation in Parkinson's Disease (PD). We also study the mechanisms by which CD8 T lymphocytes dictate the nature of inflammatory responses to cancer cells. Research in my laboratory seeks to delineate the immunologic mechanisms involved in the generation of protective anti-tumor responses in CD8 cell populations, and in developing therapies for treatment of cancer.
Our work is focused on understanding how major histocompatibility complex (MHC) molecules function in the immune response to pathogens. This simple question involves the most fundamental aspect of immunology - self/non-self discrimination.
Successful respiratory pathogens must be able to respond swiftly to a wide array of sophisticated defense mechanisms in the mammalian lung. In histoplasmosis, macrophages -- a first line of defense in the lower respiratory tract -- are effectively parasitized by Histoplasma capsulatum. We are studying this process by focusing on virulence factors produced as this "dimorphic" fungus undergoes a temperature-triggered conversion from a saprophytic mold form to a parasitic yeast form. Yersinia pestis also displays two temperature-regulated lifestyles, depending on whether it is colonizing a flea or mammalian host. Inhalation by humans leads to a rapid and overwhelming disease, and we are trying to understand the development of pneumonic plague by studying genes that are activated during the stages of pulmonary colonization. [note: Dr. Goldman will be moving to UNC in Summer 2008]
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.
Research in my lab focuses on the mechanisms by which exposure to air pollutants can enhance the susceptibility to and the severity of respiratory virus infections. Specifically, we are examining the effects of air pollutants such as diesel exhaust and cigarette smoke on influenza virus infections, using several in vitro models of the respiratory epithelium. In
collaboration with physicians from the Department of Pediatrics, 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).
This laboratory focuses on the identification of signaling pathways regulating host/bacteria interaction and the pathological consequences of a dysregulated response. Using germ free mice and gnotobiotic approaches, we investigate the functional impact of toll-like receptor (TLR) and nucleotide oligomerization domain (Nod) signaling on bacteria-mediated intestinal inflammation, colitis-associated colon cancer and intestinal response to injury (ischemia-reperfusion, radiation).
Our research is in two areas. First, we are investigating the pathogenesis of Venezuelan equine encephalitis virus (VEE). In the mouse model of VEE infection, we are examining the lymphotropic and neurotropic aspects of the disease, the initial cells targeted after inoculation, the role of viremia in invasion of the central nervous system (CNS), immune mechanisms of clearance from the CNS, and the genetics of pathogenesis. The second research area is the design of live virus vaccines, vaccine vectors and vaccine adjuvants. In animal models of several important human and animal pathogens, e.g. influenza, Marburg, Ebola, dengue fever and simian immunodeficiency virus, VEE vectored vaccines and adjuvants have proven safe, immunogenic and in most cases, protective.
Our focus is on using genetic methods to improve transplantation using ES and hematopoietic stem cells in transplant models. A second focus of the lab uses mutant mice to examine potential drug targets for ameliorating radiation-induced lung damage.
Molecular, cellular and in vivo approaches in intestine to define mechanisms by which hormones and growth factors regulate normal growth and cancer. Uses model cell lines, mutant mice, mouse models of disease, translational approaches to growth factor action and signal transduction, gut immune interactions in obesity.
My research interests focus on molecular events involved in the initiation of autoimmune response in multiple sclerosis (MS) and mechanisms of action of immunomodulatory and neuroprotective therapies for this disabling disease.
Our laboratory is interested primarily in the responses of macrophages during injury to the central nervous system and during inflammation after insult by bacterial pathogens. We use molecular, cellular and biochemical approaches both in vitro and in vivo to identify the function of key mediators during pathogenesis.
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.
Dr. Preston's research interests address fundamental genetic and biochemical questions related to autoimmune diseases that affect the kidney. A recent discovery by Dr. Preston and coworkers led to the formulation of a novel theory that delineates potential "triggers" that lead to autoantibody production (Nature Medicine 10: 72-79, 2004). Dr. Preston works closely with the research team within the UNC Kidney Center,including the Director of the Center, Ronald Falk, MD. and the Clinical Core, which obtains biologic samples
from patients for research purposes. These interactions provide the perfect setting for a truly Translational Research Program within the UNC Kidney Center
Identification of airway epithelial stem cells; innate immunity in the airway; the pathophysiology of post-lung transplant ischemia reperfusion injury and bronchiolitis obliterans syndrome.
My interests include the use of immunological and molecular probes to study function of normal and abnormal coagulation factors; the study of factors regulating human immune response to coagulation factors; and immunochemical studies of antigen-antibody interaction.
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.
Research interests center around interactions between xenobiotic compounds (ambient and indoor air pollutants as well as food allergens) and the immune system and consequent effects on infectious and allergic disease. The laboratory has developed several rodents models of infetious and allergic disease. The focus is to understand the effects that exposure to environmental agents may have on both local and systemic immune responses, the underlying mechanisms associated with these effects, the consequent impact on susceptibility to disease, and the relationship between rodent data and human health effects.
Our laboratory is involved in studies to determine the mechanisms and proteins involved in the migration of alloreactive and regulatory T cells to organs involved in graft-versus-host disease after stem cell transplantation using mouse models.
My laboratory studies development and function of the human immune system and human liver, and HIV-1/HCV infection and immuno-pathogenesis. 1. Humanized mouse models to study human hamatopoietic stem cells (HSC), thymus and liver stem cells. 2. FoxP3 and regulatory T (Treg) cells in viral infection and immuno-pathogenesis. 3. Modeling immuno-pathogenesis and immuno-therapy of chronic HIV and HCV.
The immune system is a network of interacting biological cells. The molecular events that lead to the activation and regulation of these cells often occur at the cell surface. However, little is known about the arrangement, motions and interactions of the participating cell-surface molecules. To examine these phenomena, we construct model cell membranes on planar supports from purified or synthesized molecules. Recently developed techniques in laser-based fluorescence microscopy can then be employed to examine the behavior of select fluorescently labeled molecules at or near the supported planar membranes. This research is significant not only in the basic understanding of the immune system, but also in other areas of cell-cell communication and cell membrane biophysics, in the physics of two-dimensional fluids, and in biotechnology.
Topics include gene discovery, genomics/proteomics, gene transcription, signal transduction, molecular immunology. Disease relevant issues include infectious diseases, autoimmune and demyelinating disorders, cancer chemotherapy, gene linkage.
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 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).
Our research is in viral pathogenesis and vaccine development for viral diseases that affect resource-poor countries. Specific areas of interest include a) innate immune responses to viral infection, b) vaccines for dengue fever, and c) maternal antibody interference with vaccination.
