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.
Experimental Evolution of Viruses. We use both computational and experimental approaches to understand how viruses adapt to their host environment. Our research attempts to determine how genome complexity constrains adaptation, and how virus ecology and genetics interact to determine whether a virus will shift to utilizing new host. In addition, we are trying to develop a framework for predicting which virus genes will contribute to adaptation in particular ecological scenarios such as frequent co-infection of hosts by multiple virus strains. For more information, and for advice on applying to graduate school at UNC, check out my lab website www.unc.edu/~cburch/lab.
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.
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).
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.
We are interested in basic DNA-protein interactions as related to - DNA replication, DNA repair and telomere function. We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.
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.
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 lab is focused on the development of HIV-1 vectors for gene therapy of genetic disease. In addition, we are using the vector system to study HIV-1 biology. We are also interested in utilizing the HIV-1 vector system for functional genomics.
The regulatory role of platelet membrane phosphatidylserine in blood coagulation; mechanism of protein-mediated membrane fusion in secretory processes and virus infection. Director of the Molecular & Cellular Biophysics Training Program.
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.
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.
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.
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.
We are engaged in studying the molecular biology of the human parvovirus adeno-associated virus (AAV) with the intent to using this virus for developing a novel, safe, and efficient delivery system for human gene therapy.
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.
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.
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.
A goal of the laboratory is to understand viral molecular pathogenesis in the oral cavity. We seek to understand the critical molecular interactions that occur between DNA viruses and the host that govern the development of oral disease.
Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for all cellular and viral RNAs. To this end, we are developing high-throughput RNA structure analysis technologies (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today. We then use these tools to understand otherwise daunting problems that play pivotal roles in cellular function. Current projects include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of human viruses and (ii) assembly of large biomedically important ribonucleoprotein complexes inside living cells.
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.
