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Research Areas and Description

Lymphocyte Development
Research programs in the department of Pathology focus on areas of basic immunology. Several laboratories pursue studies of lymphocyte development, with an emphasis on T cells. The laboratory of Joonsoo Kang investigates the transcription factors and signaling pathways that promote γδ versus αβ T cell lineage decisions. Eric Huseby’s laboratory studies αβ T cell repertoire selection, with an emphasis on how T cell receptor affinity and binding kinetics to MHC/peptide determine the fate of developing T cells. Leslie Berg’s laboratory studies T cell receptor signaling pathways and how these signals regulate conventional versus innate T cell development in the thymus.

Lymphocyte Activation
A second major area of focus in the department of Pathology is lymphocyte activation. Leslie Berg’s laboratory investigates tyrosine kinases involved in antigen and cytokine receptor signaling pathways, and how these signaling proteins regulate lymphocyte activation and differentiation into effector cells. Lawrence Stern studies immuno-receptor structures and subunit organization in an effort to understand how these receptors transduce signals across membranes. Francis Chan investigates the role of tumor necrosis factor (TNF) receptor family signaling pathways in the regulation of cell death, activation, and survival. Susan Swain’s group is focused on understanding CD4 T cell responses to flu viruses, with a goal of developing better vaccines. Liisa Selin’s and Raymond Welsh’s laboratories investigate the T cell response to viral infections, and the role of cross-reactive T cells generated in response to one infection which can alter the immune responses to subsequent unrelated pathogens via heterologous immunity. Joonsoo Kang’s laboratory studies immunological tolerance and the inhibition of T cell activation by regulatory T cells, focusing on the roles of checkpoint costimulatory-coinhibitory axis consisting of CD28 and CTLA-4. Reboldi’s lab is investigating how proper B cell activation and IgA production in the gut and Peyer’s patch leads to immune protection and homeostasis. He is particularly interested in how B cell positioning in germinal centers is established and regulated in secondary lymphoid tissues to ensure optimal antibody production.

Molecular Recognition - Antigen Presentation - Autoimmunity - Dendritic Cell
The department of Pathology also has a number of research programs focusing on molecular recognition events in the immune system. Kenneth Rock’s laboratory investigates the cellular enzymatic pathways that generate peptide antigens for presentation to T cells on major histocompatibility complex (MHC molecules). His lab is particularly interested in a specialized antigen presentation pathway called cross-presentation, where antigens taken up from outside a cell are presented on MHC class I molecules. Lawrence Stern’s laboratory studies the MHC class II molecules, and the cellular pathways involving DM and DO that participate in peptide loading and peptide editing for antigen presentation on MHC class II. Eric Huseby’s laboratory investigates the molecular details of TCR recognition of MHC/peptide complexes, and how subtle changes in TCR binding are translated into distinct outcomes for T cell development and activation. Kang and Berg labs are developing clinical strategies to halt autoreactive T cell migration to non-lymphoid tissues, to treat human T cell mediated organ-specific autoimmunity such as MS and colitis. Liisa Selin’s group investigates evolution of human T cell memory to influenza across different population groups of healthy, chronically infected and immune-compromised individuals. Using a combination of epidemiological, immunological and molecular biological information, this group explores how T cell memory to influenza is generated, maintained and exhausted at individual and population levels. Finally, Kang and Huseby labs collaborate to determine immune components and their activities in spontaneous atopic dermatis.

Programmed Cell Death
Programmed cell death, a cell suicide mechanism that plays crucial roles in both lymphocyte development and functions, is another area of research focus in our department. Francis Chan’s group studies the molecular mechanisms by which TNF family cytokines induce both apoptotic and non-apoptotic cell death in different lymphocyte populations. He discovered RIPK3 function in necroptosis and understanding multifaceted activities of RIPK members in immune homeostasis is a central occupation of his lab. As cells undergo programmed cell death, endogenous adjuvants or danger signals such as monosodium urate crystals (MSU) are released from the injured cell, which cause inflammation. Kenneth Rock’s group is interested in understanding how the release of MSU and other endogenous adjuvants regulate immune surveillance and induce acute inflammation. Raymond Welsh’s group is interested in the role lymphocyte cell death plays in shaping the anti-viral T-cell responses and immunological memory.

Viral Immunology
A major strength in the department is research on viral immunology. Using lymphocytic choriomeningitis virus (LCMV) and other virus infection models, Raymond Welsh’s group focuses on how innate and adaptive immune responses control viral infections and generate immunological memory. Swain lab studies CD4 T cell responses  to flu viruses and how distinct responses are programmed in infected non-lymphoid tissues. Stern and Selin labs are interested in how infection by different viruses shapes the responding T-cell receptor repertoire to alter the immune responses and associated immuno-pathologies. Francis Chan is interested in how necrotic cell injury during viral infections contributes to the initiation of innate and adaptive immunity and the mechanisms by which viruses interfere with the host cell death machineries.

Innate Immunity
Innate immune responses play crucial roles in controlling the majority of pathogenic challenges we face in our daily lives. As a natural extension of our interest in viral immunology, the department has several active research programs in the area of innate immunity. Kenneth Rock’s group is interested in studying the mechanisms by which endogenous adjuvants or “danger signals” alert the immune system during infections and in response to cell injury. Francis Chan is interested in the mechanism by which necrotic cell death contributes to innate immune control of viral infections. Raymond Welsh is interested in identifying the signals that control lymphocyte attrition and expansion during the innate phase of immune responses. Eva Szomolanyi-Tsuda examines the role of Toll-like receptors (TLRs) in the regulation of immune responses against virus infections. Leslie Berg’s group is interested in the development and functions of innate-like lymphocytes. Joonsoo Kang’s group has a major interest in identifying genes that are central for innate-like γδ T cell development, starting from embryonic tissues, prior to the emergence of the first hematopoietic stem cell.

T-cell Receptor Structure and Function 
Several groups within the department are interested in T-cell receptor structure and function analyses. Larry Stern uses a combination of biochemical and biophysical tools to address the molecular interactions between MHC/peptide complexes and T-cell receptors and their role in T-cell activation. Eric Huseby is interested in the molecular signatures within the T-cell receptor that drive T-cell development and tolerance.

Mucosal Immunity
Joonsoo Kang and Eric Huseby have an active program examining the roles of innate and adaptive lymphocyte populations in the control of infections and inflammation in the skin. Dr. Swain is studying the immune response to flu infections in the lung. Reboldi lab’s central research area is the nature of antigens recognized by gut IgA.