Mark T. Heise, Ph.D.
“Systems Genetics Approaches for Studying Viral Pathogenesis” – January 25, 2018
Professor, Departments of Genetics and Microbiology and Immunology
University of North Carolina at Chapel Hill
My laboratory is interested in understanding the interactions between viruses and the infected host that lead either to virus-induced disease or to resolution of the viral infection. Our current studies are focused on mouse pathogenesis models using alphaviruses (Genus: Togaviridae, Family: Alphavirus), mosquito borne RNA viruses that are a significant cause of encephalitis and infectious arthritis in humans. Several aspects of alphavirus biology make them tools useful for studying viral pathogenesis. The alphavirus genome is extremely amenable to genetic manipulation due to the existence of full length infectious viral cDNA clones. These infectious clones permit the introduction of defined genetic changes into the alphavirus genome for the purpose of evaluating the role of specific viral genetic elements in viral replication or virulence. The infectious clone technology also permits the construction of virus based expression vectors for tracking viral replication within the infected animal or for use in gene delivery. Alphaviruses also cause a spectrum of diseases in mice that include encephalitis and arthritis/arthralgia. Due to the availability of a wide range of genetically modified mice lacking specific immune mediators, it is possible to manipulate both the virus and the infected animal in order to define the role of viral and/or host factors in the pathogenesis of virus-induced diseases.
Gwendalyn J. Randolph, Ph.D.
“The two “trash handlers” in tissues – macrophages and lymphatics – during chronic inflammatory disease” – January 18, 2018
Emil R. Unanue Professor, Pathology & Immunology
Washington University School of Medicine, St. Louis, MO
Our laboratory considers the impact of how transit of cells and molecules out of tissues influences the inflammatory microenvironment. The lymphatic vasculature is the primary regulator of flux out of tissues and thus we focus on the functionality of the lymphatic vasculature as it relates to the transport of cargo, particularly myeloid antigen-presenting cells in immunity and molecular entities like HDL. In this context, we focus on two chronic inflammatory disease settings, experimental atherosclerosis and inflammatory bowel disease.
Shabaana A. Khader, Ph.D.
“Host Immunity to Tuberculosis: A Balancing Act” – December 7, 2017
Associate Professor, Department of Molecular Microbiology
Washington University School of Medicine, St. Louis, MO
The major goal of my lab is to define the basic requirements for induction of protective immunity in the lung against pulmonary pathogens such as Mtb. Our past work has described a novel role for the cytokine Interleukin-17 (IL-17) in vaccine-induced immunity against tuberculosis. More recent work from my lab has utilized this information to target and boost lung Th17 responses to improve vaccine-induced immunity against tuberculosis. We have identified that mucosal immunization with Mtb antigen induces a population of lung-resident Th17 cells. IL-17 made by Th17 cells mediate protection in the host by inducing formation of lymphoid follicles in the lung to initiate T cell localization near infected macrophage for Mtb control. In contrast, IL-17 is a potent proinflammatory cytokine and expression of this cytokine during TB is associated with induction of neutrophil accumulation and associated lung pathology. Thus, current approaches in the Khader lab are focused on enhancing lung Th17 responses to improve vaccine strategies for TB, without inducing the pathological effects of IL-17 mediated lung inflammation. We use cutting edge approaches involving the use of alternative routes of immunization, use of novel Th17 adjuvants, and altering the location of Th17 cells in the lung, as new ways to boost vaccine-induced immunity against TB.
Sunny Shin, Ph.D.
“Innate immune defense against intracellular bacterial pathogens” – November 9, 2017
Assistant Professor, Department of Microbiology
Perelman School of Medicine, University of Pennsylvania
My lab is interested in uncovering innate immune mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade host immunity to cause disease. A major focus of our lab is to understand how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses. We are also interested in elucidating how the immune system successfully overcomes the ability of pathogens to suppress critical immune functions.
Jennifer Herman, Ph.D.
“Regulation of essential cell processes during Bacillus development” – October 26, 2017
Associate Professor, Department of Biochemistry and Biophysics
Texas A&M University
The study of bacterial cell biology has surged in the last decade, largely due to technological advances in live-cell imaging, the discovery of new bacterial cytoskeletal elements, and the need to identify new targets and novel therapies for emerging antibiotic-resistant bacteria. As a result, we now appreciate that bacteria are highly organized creatures at the subcellular level; they localize macromolecules to specific cellular locations, often in dynamic and temporally regulated manners. Strikingly, the range of bacterial molecules with specific localizations encompasses every fundamental cellular process, including DNA replication, cell division, and secretion, not to mention specialized activities such as motility, virulence, and development into differential cell types.
The study of how bacteria organize important cellular processes and determining the functional/physiological implications of this organization for the cell is one of the most exciting areas of research in microbiology. In the Herman lab, we utilize the model organism Bacillus subtilis, a bacterium with superb molecular, genetic and cell biological tools, that that can also differentiate into a resting cell type called a spore. Our research goal is to elucidate how bacteria coordinate key biological processes, with their cellular architecture using molecular, biochemical, and cell biological techniques.
Pinghui Feng, Ph.D.
“Probing roles of protein deamidation using herpesvirus infection” – September 28, 2017
Associate Professor, Department of Molecular Microbiology and Immunology
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
Dr. Feng’s group investigates the roles of innate immune signaling pathways in infection and pathogenesis of human oncogenic gamma herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV).
Ralph R. Isberg, Ph.D.
“Control of host cell tubular endoplasmic reticulum function by Legionella pneumophila” – September 7, 2017
Professor, Department of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Sciences, Investigator, Howard Hughes Medical Institute
Tufts University School of Medicine, Boston
Our research is directed toward answering three questions concerning the lifestyle of invasive bacterial pathogens: How are intracellular pathogens able to penetrate into normally nonphagocytic epithelial cells? What factors do intracellular bacteria encode that allow them to survive and grow within the normally hostile environment of macrophages? What role do factors that are important for bacterial-host cell interaction models play in an infection of the host? We perform genetic and biochemical experiments on two bacterial pathogens, the bacterium Yersinia pseudotuberculosis, and Legionella pneumophila, the causative agent of Legionnaire’s disease pneumonia.
James E. Crowe, Jr., M.D.
“Genetic and structural basis for human antibody neutralization of viruses” – February 23, 2017
Professor, Department of Pediatrics and Pathology, Microbiology and Immunology, Ann Scott Carell Chair, and Director Vanderbilt Vaccine Center
Vanderbilt University School of Medicine
The cell biology of virus infection, genetic and structural basis for development of human neutralizing antibodies and genetic basis of adverse events following vaccination.
Matthew B. Grisham, Ph.D.
“T Cell Trafficking in Chronic Gut Inflammation: The Long and Winding Road” – October 27, 2016
Professor and Chair, Department of Immunology and Molecular Microbiology and the Vernon and Elizabeth Haggerton Chair in Gastroenterology
Texas Tech University Health Sciences Center (TTUHSC)
Inflammatory bowel disease; autoimmune diseases; chronic inflammation; cell-based therapy; mucosal immunology.
Michael S. Diamond, M.D., Ph.D.
“Host Immunity and Pathogenesis of Zida Virus Infection” – September 8, 2016
Professor, Departments of Medicine, Molecular Microbiology, Pathology and Immunology; and Head, Division of Infectious Diseases and Vaccine Development
Washington University School of Medicine
The research in the Diamond laboratory focuses on the interface between viral pathogenesis and the host immune response. For several years, we have been primarily focused on two globally important mosquito-borne human pathogens, West Nile virus and Dengue virus. Both are single-stranded positive-sense RNA viruses of the same genus (Flavivirus) that cause human disease worldwide. Recently, we have begun to study other emerging viral infections including Zika and Chikungunya viruses as well as new bunyaviruses. We are interested in defining mechanisms of innate immune restriction and viral immune evasion, generating novel mouse models and understanding the epitope specificity of protective antibodies. In addition, studies also now focus on the use of high throughput CRISPR/Cas9 whole genome screens to identify host factors required for these viral infections.
Frances E. Lund, Ph.D.
“Regulation of B lymphocyte cell fate decisions by Tbox Proteins” – February 4, 2016
Professor and Chair, Department of Microbiology
University of Alabama at Birmingham
The overarching research objective of the Lund laboratory is to identify the key players that suppress or exacerbate mucosal inflammatory responses with the long-term goal of developing therapeutics to treat immunopathology associated with chronic infectious, allergic and autoimmune disease. One of the lab’s major projects is to characterize the roles that cytokine-producing “effector” B cells play in modulating inflammation and T cell-mediated immune responses to pathogens, autoantigens and allergens. In a second project, the lab evaluates how inflammatory signals regulate the balance between the development of the antibody-producing long-lived plasma cells and the memory B cell compartment within lymphoid tissues. The lab also studies how these cells are maintained long-term at inflammatory sites. Finally, the lab examines how oxidative stress induced by reactive oxygen species impacts inflammation, immune responses and cellular metabolism. In particular, the lab is experimentally modulating the NAD metabolome of immune cell in order to alter the responsiveness of these cells to oxidative stress.
Dirk P. Dittmer, Ph.D.
“Trying to understand viral lymphoma” – January 7, 2016
Professor, Department of Microbiology and Immunology
University of North Carolina at Chapel Hill
By current estimates, 25-35% of all human cancers are of viral origin or require viral infection as an essential cofactor. The goal of our research is to understand viral tumorigenesis, specifically, cancers that are caused by Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8). KSHV is a double-stranded DNA virus of about 120kbp, which belongs to the rhadinovirus family of human herpesviruses. It was discovered in 1994 and is associated with Kaposi’s sarcoma (KS) as well as B-cell lymphoproliferative diseases such as primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). These diseases are ultimately fatal, as they affect internal organs and, in the U.S., are usually seen in the context of immunosuppression such as that found in HIV-positive individuals or transplant patients.
Edward Pearce, Ph.D.
“Metabolic control of innate immunity” – February 19, 2015
Senior Group Leader, Max Planck Institute of Immunobiology and Epigenetics, and Professor, Faculty of Biology, University of Freiburg, Freiburg, Germany.
Immunobiology, schistosomiasis, CD4+ T cell, dendritic cells, macrophages – Dr. Pearce’s laboratory studies innate and adaptive immune responses during chronic infection with the intravascular helminth parasite, Schistosoma mansoni, particularly the development/regulation of Th2 responses, which dominate during helminth infections, and the interplay between Th2 cells and cells of the innate system. In the context of schistosomiasis, Th2 cells serve a protective role in this setting, allowing the host to survive while infected, and yet simultaneously cause the development of immunopathologic changes that can become severe as the infection progresses.
Marc K. Jenkins, Ph.D.
“Tracking the activation of helper T cells during infection” – January 15, 2015
Distinguished McKnight University Professor
Director, Center for Immunology, Department of Microbiology, Northwestern University
Current President of the American Association of Immunologists
CD4+ T and B lymphocyte biology – Dr. Jenkins and his colleagues investigate CD4+ T and B cell activation in vivo by directly tracking antigen-specific cells. The goal of this research is a basic understanding of lymphocyte activation that can be used to improve vaccines and prevent autoimmunity.