Microbiology and Immunology Research Overview - Molecular Pathology

Research Overview - Microbiology and Immunology

Introduction: Although microbiology is one of the oldest medical sciences, dating to the end of the 19th century, it is still an exciting, dynamic and expanding discipline. In the last decade alone several new bacterial and viral pathogens have been discovered, and we have had to face the growing problem of antimicrobial drug resistance. More than a score of bacterial genomes have been sequenced and more genome sequences are on the way. There are several new and powerful tools for studying microbial pathogenesis, and for studying the remarkable interactions between pathogens and host cells.

Bacterial and fungal infections: Dr. Nizet studies human streptococcal pathogens, adopting a molecular genetic approach to discover and characterize virulence determinants involved in cytotoxicity, adherence, invasion, inflammation and resistance to immunologic clearance. Dr. Gallo's laboratory discovered the presence of antimicrobial peptides in mammalian skin, and showed through gene targeting techniques that such peptides are essential for defense of the skin against invasive bacterial infections. They have demonstrated correlation to human disease. Dr. Fierer's laboratory studies innate and acquired resistance to infection of Salmonella sp., focusing on roles of polymorphonuclear leukocytes (PMN) and serum complement in resistance. He and Dr. Kirkland also study the basis for genetic susceptibility of inbred mouse strains to Coccidioides immitis and the role of IL-10 in genetic resistance to this fungus. Dr. L Corbeil's group addresses virulence factors and protective host responses of Haemophilus somnus, focusing on the role of immunglobulin binding proteins on the surface of H. somnus in pathogenesis and the role of specific antibody isotypes and allotypes in immunity.

Protozoan infections: Dr. Gillin's group studies the molecular and cellular biology, genomics, and host-parasite interactions of Giardia lamblia. Dr. L. Corbeil's group is investigating mechanisms of protective immunity and pathogenesis at the genital mucosa in trichomoniasis. Roles of surface lipophoshphogycan and secreted cysteine proteinase are studied in murine and bovine animal models as well as in vitro. Dr. Reed's group focuses on elucidating the mechanisms of virulence of Entamoeba histolytica, which causes amebic liver abscesses and dysentery, and of Toxoplasma gondii, which causes sever congenital and reactivation diseases in immunocompromised patients, such as those on transplantation medication or those with AIDS.

Viral infections: Dr. Guatelli's research is focused on the molecular virology of HIV-1. Specifically, they study the Nef gene product of HIV-1, a small peripheral membrane protein which is important for pathogenesis and affects membrane trafficking and signal transduction in infected lymphocytes. Dr. J. Corbeil applies functional genomics to analyze the relationship between infectious agents and their hosts. They have generated exciting insights for HIV infection of CD4+ T cell and macrophages using high-density microarray technology for quantitative, simultaneous monitoring of thousands of genes. Dr. Torbett has developed gene delivery vectors from HIV-1 to target human hematopoietic cells for the delivery of novel HIV inhibitory products and investigates the structural and biochemical aspects of HIV-1 protease inhibitor resistance. HIV drug resistance was originally recognized in Dr. Richman's laboratory in 1988. In addition to his continuing interest in HIV treatment and drug resistance, his research interests have focused on HIV pathogenesis including the issues of viral latency, evolution and immune responses.

Mucosal immunology: Dr. Nizet studies the role of cationic antimicrobial peptides in defense against invasive bacterial infection. Dr. Kagnoff's group studies innate mucosal immunity with a focus on the mechanisms by which pathogenic microbes signal host epithelial cell responses, the signals produced by intestinal epithelium that activate mucosal immunity, and the importance of key epithelial signaling pathways for host protection. These studies use a spectrum of in vitro and in vivo model systems. The laboratory of Dr. L. Corbeil also studies mucosal immune responses to sexually transmitted infections in the reproductive tract to ask whether they contribute to protection or pathogenesis.Dr. Gillin's group investigates Giardia -host interactions in the GI tract.

The immune response: Pathogen clearance is mediated by both innate (monocyte, neutrophil, etc.) and acquired (B and T lymphoid) immunity. Dr. Varki's research focuses on the role of extracellular protein glycosylation, which is involved in numerous physiological systems, including the innate immune responses of neutrophils and monocytes that require their adhesion and migration out of the vasculature. Dr. Ho's research focuses on the acquired immune responses of T cells, specifically of the mechanisms regulating gene transcription during T cell development and activation. Dr. Wilson's laboratory focuses on X-ray crystal structure determination of the T cell receptor and related signal transduction molecules involved in T cell activation.

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