Coronaviruses, including SARS and Noroviruses are used as models to study the genetics of RNA virus transcription, replication, persistence, cross species transmission and vaccine development.
We study the cell biology of the protozoan parasites that cause Toxoplasmosis and Malaria, especially the mechanism and control of parasite motility and host cell interaction.
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.
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.
Cellular and molecular basis of the mucociliary clearance system in the airways of the lung. Our focus is on the regulation of mucin secretion and ciliary activity at the cell and molecular levels.
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 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.
We are interested in uncovering the fundamental systems-wide processes and mechanisms that underlie life, with a human-health focus. We apply a combination of both modern and traditional tools to this pursuit, including bioinformatics, proteomics, microarrays, molecular genetics, bench work, and software development. Current research areas we focus on include: 1) locating the molecular mechanisms that underlie antibiotic tolerance in the bacteria Pseudomonas aeruginosa, to address the threat that drug resistant organisms pose to those with COPD and Cystic Fibrosis; 2) annotation of the human genome with proteomic data, to determine which genes are translated and when, and how those correlate with prevalent diseases such as cancer; 3) development of computational agent-based models of intramolecular pathways and pathogen-host interactions in HIV, to determine how host-pathogen interactions relate to disease progression; 4) development of software tools for analysis of RNA structures, such as the viral HIV genome, to assist with determining how RNA structure impacts function; and 5) developing software for finding post-translational modifications (PTMs) on proteins by integrating proteomic data sets, to determine the role that these play on cellular signaling in healthy and diseased states. We have a wide diversity lab members, from microbiology bench scientists to computer scientists, and would be a great fit for a student looking for a broad, cross-disciplinary training environment focused on either microbiology and/or genomics.
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]
Our research goal is to understand how bacterial pathogens cause disease on their hosts. We are working with a plant pathogen, Pseudomonas syringae which introduces virulence proteins into host cells to suppress immune responses. Our laboratory collaborates with Jeff Dangl's lab in the UNC Biology Department using genomics approaches to identify P. syringae virulence proteins and to discover how they alter plant cell biology to evade the plant immune system and cause disease.
Dr. Gulley's research is on Epstein-Barr virus (EBV)-related malignancies. Molecular and immunohistochemical techniques are used to characterize infected tissues. We validate new assays to help diagnose and monitor affected patients.
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.
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.
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).
My lab studies the pathogenic mechanisms of two bacterial pathogens, Haemophilus ducreyi and Francisella tularensis. H. ducreryi, the agent of the sexually transmitted infection chancroid, somehow inhibits the development of an effective immune response
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.
Protein-derived radicals, in vivo detection of free radical generation, biomarkers of oxidative stress and free radical formation in aids-related infection (Pseudomonas aeruginosa)
Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis. 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.
Dr. Meshnick studies the molecular epidemiology of malaria and HIV, especially in pregnant women through collaborations in Malawi, the Democratic Republic of the Congo, Thailand and Cambodia. His group is also developing and using novel molecular assays to study the epidemiology and clinical significance of antimalarial drug resistance and to understand the mechanisms of action of antimalarial drugs. His group is also interested in understanding the mechanism of HIV transmission from mother to child and identifying risk factors. Currently, he is using whole genome analyses to further dissect risk factors for transmission.
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. [Note: I will be moving my laboratory to UNC-CH in the summer of 2008]
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.
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.
Our laboratory investigates the role of the Epstein-Barr virus in the etiology of human disease. EBV is a ubiquitous infectious agent, which is associated with specific malignancies including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma (NPC), which develop with high incidence in endemic areas. EBV is etiologic for post-transplant lymphoma and also causes the AIDS-associated disease, hairy leukoplakia (HLP). We have identified three viral genes, which are consistently expressed and have identified a new family of transcripts that are expressed at particularly high levels in NPC tissue. These new mRNAs are intricately spliced and contain several new open reading frames which could potentially code for protein. We have shown one of these open reading frames does encode a protein that is expressed at high levels in EBV associated cancers. Current studies are investigating the potential functions of this gene using the two hybrid analysis in yeast cells and by determining its intracellular location with confocal microscopy.
Identification of airway epithelial stem cells; innate immunity in the airway; the pathophysiology of post-lung transplant ischemia reperfusion injury and bronchiolitis obliterans syndrome.
The intestine harbors a large and diverse community of microorganisms. This gut microbiota impacts upon many aspects of host biology, including nutrient metabolism, immunity, and epithelial cell renewal. Our lab is using genetic and molecular methods in gnotobiotic zebrafish hosts and in selected members of the gut microbiota, to investigate the mechanisms underlying evolutionarily-conserved host-microbial interactions in the vertebrate digestive tract.
Keywords: intestine, microbiota, bacteria, symbiosis, commensalism, immunity, inflammation, metabolism, obesity, germ-free, gnotobiotics, zebrafish
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.
FFirst, 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.
Dr. Tidwell's research is focused on the design and synthesis of new drugs for the treatment of AIDS-associated opportunistic infections. The rationale for design of new drugs is directed at determining the mechanisms of action, antimicrobial activity, and pharmacokinetics of dicationic molecules. Studies have been initiated to isolate and identify new drug targets from Pneumocystis carinii and Cryptosporidium parvum utilizing molecular modeling and biochemical methods to aid in the determination of new structures. The role of proteases and imidazoline receptors in the pathogenesis of disease continues to be a major area of research as well as a new prodrug approach for the cationic molecules to allow for much improved bioavailability.
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 focuses on the mechanisms used by the bacterium Pseudomonas aeruginosa to cause disease. We are interested in identifying signal transduction pathways that regulate the expression of virulence genes in response to the host environment.
