Inflammation

Christopher Allen 

Asthma is a complex disease of the lung with persistent underlying inflammation. The lab is using two-photon microscopy and other advanced techniques to study the cellular interactions among inflammatory cells in the lungs and associated lymphoid tissues.

Other Research in Dr. Allen's Lab:

Allergy and AsthmaImmune RegulationImmune Receptors and Signaling

 

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 ImmunityImmune Receptors and Signaling 

 

Harold 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 Harold A. Chapman. 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 AsthmaAutoimmunity 

 

Laurence Cheng

Allergic inflammation represents a specific inflammatory module that is closely tied to the immune response observed during parasite infection or in human allergic diseases.  The hallmarks of this inflammatory response include tissue eosinophil accumulation and elevated IgE levels.  A major goal of the laboratory is to understand how IgE drives chronic allergic inflammation.  We have developed a model system which indicates that IgE binding to antigen drives an inflammatory 'switch' toward allergic inflammation in the skin.  Though both mast cells and basophils are capable of binding and responding to IgE, only basophils are required to mediate this response.  Using animal models of disease, we are working to understand the product(s) that basophils produce to drive this switch and the cellular targets of these factors.  Ongoing efforts are also being made to use patient samples to investigate whether human disease demonstrates analogous findings.

Other Research in Dr. Cheng's Lab 

Allergy and AsthmaImmune Regulation

 

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 

 

Judith Hellman

We are studying the role of innate immune pathways in systemic and organ inflammation and coagulopathy induced by bacterial sepsis as well as by non-infectious acute inflammatory disorders such as lung ischemia-reperfusion injury. Through our studies on TLR2-dependent endothelial signaling, we have recently identified ERK5 as a key mediator of inflammatory activation of endothelial cells and monocytes/macrophages. We are now delving more deeply into ERK5 as a central mediator of inflammation in a variety of acute disorders, including both infectious and non-infectious processes. We have recently also be studying the immunomodulatory effects of the endocannabinoid system. We have found that an endogenous cannabinoid, N-arachydonoyl dopamine down regulates endothelial activation by TLR agonists and by TNF. We are continuing to characterize the endothelial endocannabinoid system and to define its role in sepsis and other acute inflammatory disorders.

Other Research in Dr. Hellman's Lab: 

Immune Receptors and SignalingImmune Response to Microbial Pathogens 

 

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 DifferentiationImmune RegulationImmune Response to Microbial Pathogens 

 

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 AutoimmunityImmune Receptors and Signaling 

 

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 RegulationImmune Receptors and SignalingImmune Response to Microbial Pathogens • 

Diabetes and Autoimmunity

 

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 DifferentiationImmune Regulation

 

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 ImmunityDiabetes and Autoimmunity

 

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 interested in understanding the interplay between this cytokine and other inflammatory cytokines during viral and host interactions.

Other Research in Dr. Sanjabi's Lab:

HIV and Viral ImmunityImmune Response to Microbial PathogensImmune Regulation

 

Dean Sheppard 

We study the immediate and long-term adverse consequences of tissue inflammation. Much of this work focuses on how members of the integrin dynamically regulate tissue inflammation, vascular permeability and tissue fibrosis. Through this approach we have developed novel treatments for acute lung injury, septic shock and pulmonary fibrosis and are working toward the development of new treatments for fibrosis of the liver, kidney and skin. 

Other Research in Dr. Sheppard's Lab: 

Allergy and Asthma

 

Zena Werb 

Inflammatory cells contribute to development of adipocytes and epithelial ducts.  We are studying the molecular mechanisms and molecules, including matrix metalloproteinases,  by which myeloid cells contribute to epithelial development, tissue repair and how these cell populations change during tumor progression.

Other Research in Dr. Werb's Lab:

Tumor Immunology Development and Differentiation