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Jody Baron
Our lab seeks to identify the cell types, and cytokines involved in the immunopathogenesis of chronic hepatitis B virus infection, virus-induced liver disease, and hepatocellular carcinoma in our transgenic mouse model. Previous experiments in our lab focus on characterization of the acute hepatitis and lymphocytes extracted from the livers of animals which had acute hepatitis, 2, 3, and 4 days after adoptive transfer of naïve, syngeneic splenocytes. Our current experiments now include identifying the cell types and cytokines involved in the chronic phase of the disease. Dr. Baron's web page.
Other Research in Dr. Baron's Lab
HIV and Viral Immunity • Immune Receptors and Signaling
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Hal Chapman
The lab is currently focused on mechanisms of epithelial injury and matrix remodeling in the context of inflammatory lung disease. We are currently pursuing two questions in this area: what are the mechanisms underlying the fate decision by epithelial cells to either undergo epithelial to mesenchymal transition (EMT) or undergo apoptosis in response to the cytokine TGFb1 ? This question gets at the mechanisms of how TGFb1 is activated and signals. And secondly, how does relative excess of interferon-gamma in the alveolar compartment lead to epithelial apoptosis and emphysema? We have already established that this is a cathepsin S dependent process but the underlying mechanism is obscure.
We are using a combination of transcriptional profiling, ex vivo studies of primary cells, and molecular genetic approaches selectively targeting specific integrins in airway cells to test our hypotheses.
Recent relevant publications:
Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, Desanctis G, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-{gamma}-Induced Alveolar Remodeling and Pulmonary Emphysema. J Immunol 2005; 174: 8106-8115.
Kevin K. Kim, Matthias C. Kugler, Paul J. Wolters, Liliane Robillard, Michael G. Galvez, Alexis N. Brumwell, Dean Sheppard and Chapman HA. Alveolar Epithelial Cell Mesenchymal Transition Develops in vivo during Pulmonary Fibrosis and is Regulated by the Extracellular Matrix. Proc Natl Acad Sci 2006, in press.
Other Research in Dr. Chapman's lab
Allergy and Asthma •
Autoimmunity
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Lisa Coussens
The overall goal of our research program is to define cellular, molecular and microenvironmental determinants of cancer development. My research is based upon the premise that, in addition to intrinsic changes occurring within neoplastic cells, e.g., activation of oncogenes and inactivation of tumor suppressor genes, extrinsic factors, e.g., inflammation, extracellular matrix (ECM) remodeling and angiogenesis also regulate critical properties of tumor evolution.
During the early development of cancer, many physiological processes occur in the vicinity of 'young tumor cells' that are similar to processes that occur during embryonic development and to healing of wounds in adult tissue, e.g., leukocyte infiltration, activation of pre-existing vasculature and development of new blood supply (angiogenesis) and extensive tissue remodeling. During wound healing, immune cells are recruited to sites of injury to eliminate potential bacterial infection as well as to facilitate healing by providing growth factors and proteases that are essential to the process. In so doing, tissue remodeling occurs and accommodates generation of a new blood supply that further helps the tissue heal. When 'healing' is complete, inflammation and tissue remodeling resolves and the tissue returns to its former state. Several of these parameters are conserved during tumor development; however, instead of initiating a 'healing' response, inflammatory cells, tissue remodeling and angiogenesis provide growth-promoting factors that promote tumor development. By studying mouse models of skin and breast cancer development, the Coussens lab is identifying important cellular pathways and molecules involved in regulating tumor-associated inflammation, tissue remodeling and angiogenesis. Identification of these important regulatory mechanisms will reveal drug-targets that can then be used to design novel therapeutic strategies for treating and imaging cancer development in humans.
Other Research in Dr. Coussen's lab
Tumor Immunology
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Warner Greene
My laboratory has maintained a long-standing interest in NF-kappaB/Rel transcription factors, principal mediators of the inflammatory response. Our studies are currently focusing on intranuclear events that control the magnitude and duration of the NF-kappaB/Rel transcriptional response. These studies have also led us into the function of NF-kappaB/Rel factors in the brain and the link of these factors to learning and memory.
Other Research in Dr. Greene's Lab
HIV and Viral Immunity
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Richard Locksley
Helper T cells and the cytokines IL-4 and IL-13 have been implicated in many aspects of allergy and asthma. The lab uses several mouse models of allergic immunity to study the initiation and maintenance of innate and adaptive Th2 cells that sustain the allergic state by following the fates of cells marked by their expression of various important cytokines.
Other Research in Dr. Locksley's lab:
Development and Differentiation • Imune Regulation • Immune Response to Microbial Pathogens
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Cliff Lowell
The focus of the lab is on signaling in innate immune cells, which directly affects the ability of these cells to initiate inflammatory reactions. Hence, many of our knockout strains are evaluated in various inflammatory (and bacterial infectious) disease models. Mutations in these signaling pathways alters (either decrease or in some cases actually increase) inflammatory responses.
Other Research in Dr. Lowell's Lab
Diabetes and Autoimmunity • Immune Receptors and Signaling
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Averil Ma
Our work on intracellular mechanisms of coordinating signal transduction events has focused on the molecule A20. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that stimulates multiple cellular activation and survival signaling pathways. By targeting the TNF induced A20 gene, we found that A20 deficient mice develop profound autoimmunity coupled with an inability of A20 deficient cells to terminate TNF induced NF-kB responses (Lee et al, Science 2000). We subsequently generated A20 TNF and A20 TNFR double mutant mice, and found that A20 is critical for regulating toll-like receptor (TLR) induced NFkB signals that commit both innate and adaptive immune responses (Boone et al, Nature Immunology 2004). Moreover, we have found that A20 is also critical for terminating JNK signals. Thus, A20 mediates cross-talk between NFkB and JNK signaling pathways. Moreover, we have found that A20 is a unique ubiquitin modifying enzyme that requlates both the activity and stability of signaling proteins Wertz et al, Nature 2004; Boone et al, Nature Immunology 2004). A20 is thus a biochemically unique molecule that is critical fro regulating multiple signaling pathways and biological processes that depend on these pathways. Recent studies indicate A20 is expressed in T cells and dendritic cells, and may play critical roles in regulating both innate and adaptive immune responses. Ongoing studies focus on the physiological targets of A20’s enzymatic activity, the biochemical mechanisms by which A20 functions, the regulation of A20 activity, and the roles of A20 in regulating T cell and dendritic cell activation and survival.
Other Research in Dr. Ma's Lab
Immune Regulation • Immune Receptors and Signaling • Immune Response to Microbial Pathogens •
Diabetes and Autoimmunity
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Emmanuelle Passegué
Our laboratory studies the mechanisms driving aberrant myeloid differentiation from the blood-forming hematopoietic stem cells (HSCs) to identify molecular targets for the treatment of myeloid disorders such as myeloproliferative neoplasms (MPN) and chronic inflammation.
Other Research in Dr. Peters' Lab
Development and Differentiation • Immune Regulation
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Marion Peters
The liver is the first line of defense against gut derived antigens and pathogens entering via the portal vein. It must maintain a balance between tolerance to incoming antigens and generation of an immune response. It is rich in immune cells whose composition and state of activation differ from those of other lymphoid organs. This proposal will test the hypothesis that innate and adaptive immune cells specific to the liver actively regulate biliary directed liver inflammation. We have developed transgenic mice, which express chicken ovalbumin (OVA) on the surface of biliary epithelium. These OVA-BIL mice are tolerant to OVA because of protein expression in the thymus during development. The mice develop normally and have shown no evidence of liver or other disease. However adoptive transfer of OVA specific CD4+ (OT-II) and CD8+ (OT-I) T lymphocytes results in biliary centered inflammation which is self limited. We have characterized the cells and cytokines involved in this inflammatory response. Understanding the mechanisms involved in the development and control of this inflammation, including which responses are critical for limiting disease, which are adaptive and which are innate, is essential to understanding the pathogenesis of many liver diseases and to develop novel and specific methods to interfere in the progress of such diseases.
Other Research in Dr. Peters' Lab
HIV and Viral Immunity • Diabetes and Autoimmunity
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Steve Rosen
The Rosen lab is studying the contribution of the L-selectin adhesion system in asthma and rheumatoid arthritis. Several mouse models of rheumatoid arthritis are being tested in conjunction with mice that are null for L-selectin and for sulfotransferases involved in the synthesis of endothelial ligands for L-selectin.
Other Research in Dr. Rosen's lab:
Development and Differentiation • Immune Receptors and Signaling • Tumor Immunology
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Shomyseh Sanjabi
TGFβ is best known as an anti-inflammatory cytokine; however, it is also induced during acute inflammatory conditions and it controls the number of activated lymphocytes. We are also interested in understanding the role of this cytokine under chronic inflammatory conditions such as HIV infection, tumors, and autoimmunity.
Other Research in Dr. Sanjabi's lab
HIV and Viral Immunity • Immune Response to Microbial Pathogens • Immune Regulation
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Zena Werb
Inflammatory cells contribute to development of adipocytes and epithelial ducts in the mammary gland. We are studying the mechanisms by which macrophages and mast cells contribute to pubertal development and post-lacational involution.
Other Research in Dr. Werb's lab
Immune Response to Microbial Pathogens • Tumor Immunology • Development and Differentiation
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