GC399TR AN INHIBITOR OF AUTOIMMUNITY
Emanual M Maverakis, Assistant Professor
East Bay Institute For Research And Educ, Martinez, Ca 94553-4668
Grant 5K08AI075029-03 from National Institute Of Allergy And Infectious Diseases
Keywords: Angiogenesis Antagonists; Angiogenesis Blockers; Angiogenesis Inhibitors; Angiogenetic Antagonists; Angiogenic Antagonists; Angiostatic Agents; Animal Model; Animal Models and Related Studies; Animals; Anti-Angiogenetic Agents; Anti-Angiogenic Agents; Anti-Angiogenic Drugs; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-inflammatory; Antiangiogenesis Agents; Antiangiogenic Agents; Antibodies; Antiinflammatories; Antiinflammatory Agents; Autoimmune Status; Autoimmunity; Binding; Binding (Molecular Function); Binding Sites; Biochemistry; Biology; Blood Coagulation Factor I; Blood Coagulation Factor One; Blood Factor One; Blood Vessels; Body Tissues; C-terminal; C57BL/6 Mouse; CD11b; CR3A; Cell Communication and Signaling; Cell Function; Cell Process; Cell Signaling; Cell Surface Receptors; Cell physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Chemistry, Biological; Chronic; Clinical; Coagulation Factor I; Coagulation Factor One; Combining Site; Consumption Coagulopathy; DNA Molecular Biology; Dermatology; Development; Diagnosis; Disease; Disorder; Disseminated Intravascular Coagulation; Docking; Doctor of Medicine; EAE; Encephalomyelitis; Encephalomyelitis, Allergic; Endothelial Cells; Experimental Allergic Encephalitis; Experimental Allergic Encephalomyelitis; Experimental Autoimmune Encephalitis; Experimental Autoimmune Encephalomyelitis; Extracellular Matrix, Integrins; Factor I; Factor One; Fibrinogen; Goals; Hortega cell; Human; Human, General; INFLM; ITGAM; ITGAM gene; Immune response; Immune system; Immunologist; Immunology; Immunology (Including BRMP); Immunology (NCI Program); In Vitro; Inflammation; Inflammatory; Inhibitors, Angiogenetic; Inhibitors, Angiogenic; Integrin Binding; Integrins; Intracellular Communication and Signaling; Learning; M.D.; MAC-1; MAC1A; MO1A; Mammals, Mice; Man (Taxonomy); Man, Modern; Measures; Mediating; Mentors; Mice; Microglia; Molecular Biology; Molecular Interaction; Murine; Mus; Myeloencephalitis; Neovascularization Inhibitors; Organism-Level Process; Organismal Process; Physicians; Physiologic Processes; Physiological Processes; Play; Prevention; Property; Property, LOINC Axis 2; Reactive Site; Receptors, Cell Surface; Research; Role; Scientist; Signal Transduction; Signal Transduction Systems; Signaling; Subcellular Process; Surface; T-Cells; T-Lymphocyte; Testing; Therapeutic Agents; Thymus-Dependent Lymphocytes; Tissues; Training; Tube; Wound Healing; Wound Repair; angiogenesis; antiangiogenic; anticancer research; autoantibody inhibitor; autoimmune encephalomyelitis; autoimmunity inhibitor; base; biological signal transduction; body system, allergic/immunologic; cancer research; disease/disorder; fibrinogen-gamma chain; fibrinopeptides gamma; gitter cell; host response; immunoresponse; in vivo; interest; macrophage; mesoglia; microglial cell; microgliocyte; migration; model organism; mutant; new growth; organ system, allergic/immunologic; perivascular glial cell; prevent; preventing; self recognition (immune); simulation; social role; thymus derived lymphocyte; tissue repair; tumor; tumor growth; vascular
Project start date: 2008-03-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-06-512
5K08AI075029-03 (2010): $118995
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Emanual M Maverakis
CHARACTERIZATION OF PATHOGENIC T CELLS IN ALOPECIA AREATA
Emanual M Maverakis, Assistant Professor
University Of California Davis, Office Of Research - Sponsored Programs, Davis, Ca 95618
Grant 1R03AR059312-01 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases
Abstract: In order to improve the treatment regimen of patients with autoimmunity it is critical to better define the pathogenic T cell population involved. To accomplish this we will take advantage of a novel application that for the first time will allow a highly focused dissection of the pathogenic T cell repertoire. This analysis will bridge the gap that hitherto existed in understanding the effector mechanisms of an autoreactive immune response, using alopecia areata as a prototypic example. Since severe cases of alopecia areata are rarely managed with systemic agents, this organ-specific autoimmune disease represents a unique opportunity to longitudinally characterize the evolution of an autoreactive immune response in vivo in the absence of confounding immunosuppressive medications. No study to date has followed in detail an autoreactive repertoire longitudinally from a patient´s initial presentation to the establishment of chronic autoimmunity. The specific hypothesis being tested is that pathogenic self-directed T cells can be identified, characterized and followed longitudinally in patients with alopecia areata by combining CDR-3 length repertoire analysis with magnetic sorting and flow cytometry. The goal will be to determine how this pathogenic T cell response evolves over time, the surface phenotype of the pathogenic T cells, and the in vivo or directly ex vivo cytokine secretion profile of the individual pathogenic T cells. The specific aims are as follows. Specific Aim 1 Identify activated clonotypic T cells in patients with alopecia areata. Specific Aim 2 Determine if the same clonotypic T cell expansions are present longitudinally as a patient´s disease evolves. Specific Aim 3 Determine the pathogenic T cell´s surface expression of activation markers, chemokine receptors, and integrin adhesion molecules as well as the pathogenic T cell´s cytokine secretion profile. Under normal circumstances the immune system protects against foreign invading pathogens such as bacteria and viruses. The T cells are a type of cell of the immune system. These cells have the ability to distinguish viral and bacterial proteins from enogenous "self" proteins and cells that make up your body. Alopecia areata is an autoimmune disease. In autoimmunity the usually protective T cells mistakingly recognize enogenous "self" proteins as foreign, which leads to tissue and organ damage. We propose to study these T cells to determine how the autoimmune disease response evolves over time. We will also characterize the surface of the autoreactive T cells and the molecules they secrete
Keywords: ATGN; Adhesion Molecule; Alopecia Areata; Animal Model; Animal Models and Related Studies; Animals; Antigens; Autoimmune Diseases; Autoimmune Status; Autoimmunity; B cell activating factor; B cell growth factor; B-Cell Differentiation Factor-1; B-Cell Growth Factor-1; B-Cell Growth Factor-I; B-Cell Proliferating Factor; B-Cell Stimulating Factor; B-Cell Stimulating Factor-1; B-Cell Stimulation Factor-1; B-Cell Stimulatory Factor-1; BAF; BCDF-1; BCGF; BCGF-1; BCSF 1; BSF-1; BSF1; BSF1 (B cell stimulating factor 1); Bacteria; Bacterial Gene Proteins; Bacterial Proteins; Binetrakin; Biological Models; Biopsy Sample; Biopsy Specimen; Blood; Body Tissues; CD62L; CDR3-region; CTLA-8; CTLA8; Cell Adhesion Molecules; Cell Isolation; Cell Segregation; Cell Separation; Cell Separation Technology; Cell surface; Cells; Characteristics; Chronic; Chronic Disease; Chronic Illness; Cytofluorometry, Flow; Cytotoxic T-Lymphocyte-Associated Antigen 8; Cytotoxic T-Lymphocyte-Associated Serine Esterase 8; DISSEC; Diagnosis; Disease; Disease model; Disorder; Dissection; Drugs; Event; Evolution; Expression Profiling; Expression Signature; Extracellular Matrix, Integrins; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; Gene Expression; Gene Products, Bacterial; Goals; HLHRC; IL-17; IL-17A; IL-4; IL17; IL17 Protein; IL17A; IL4; IL4 Protein; Immune response; Immune system; Immunology; Immunology (Including BRMP); Immunology (NCI Program); Immunosuppressants; Immunosuppression Effect; Immunosuppressions (Physiology); Immunosuppressive Agents; Immunosuppressive Effect; In Vitro; Individual; Integrins; Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8); Interleukin 17 Precursor; Interleukin-17; Interleukin-4; Interleukin-4 Precursor; Invaded; LAM-1 gene; LECAM1; LNHR; LSEL; LYAM-1; LYAM1; Length; Lymphocyte; Lymphocyte Stimulatory Factor 1; Lymphocytic; MCGF-2; Magnetism; Mast Cell Growth Factor-2; Medication; Microfluorometry, Flow; Model System; Models, Biologic; Molecular Fingerprinting; Molecular Profiling; Natural immunosuppression; Organ; Patients; Peripheral; Pharmaceutic Preparations; Pharmaceutical Preparations; Phenotype; Play; Population; Process; Proteins; Protocols, Treatment; RGM; Regimen; Reticuloendothelial System, Blood; Role; SELL gene; Selectin L Gene; Severity of illness; Skin; Sorting - Cell Movement; Specificity; Surface; System; System, LOINC Axis 4; T-Cell Growth Factor 2; T-Cells; T-Lymphocyte; TQ-1; Testing; Thymus-Dependent Lymphocytes; Time; Tissues; Treatment Protocols; Treatment Regimen; Treatment Schedule; Viral; Virus; Viruses, General; alopecia circumscripta; autoimmune disorder; autoreactive T cell; base; body system, allergic/immunologic; cell adhesion protein; cell sorting; cell type; chemokine receptor; chronic disease/disorder; chronic disorder; complementarity-determining region 3; cytokine; disease severity; disease/disorder; disorder model; drug/agent; flow cytophotometry; gene product; host response; immunogen; immunoresponse; immunosuppression; immunosuppressive; improved; in vivo; insight; interest; intervention development; lymph cell; magnetic; model organism; molecuar profile; molecular signature; new approaches; novel; novel approaches; novel strategies; novel strategy; organ system, allergic/immunologic; patchy loss of hair; pathogen; pelade; public health relevance; response; self recognition (immune); social role; sorting; therapy development; third complementarity-determining region; thymus derived lymphocyte; treatment development
Relevance: Under normal circumstances the immune system protects against foreign invading pathogens such as bacteria and viruses. The T cells are a type of cell of the immune system. These cells have the ability to distinguish viral and bacterial proteins from enogenous "self" proteins and cells that make up your body. Alopecia areata is an autoimmune disease. In autoimmunity the usually protective T cells mistakingly recognize enogenous "self" proteins as foreign, which leads to tissue and organ damage. We propose to study these T cells to determine how the autoimmune disease response evolves over time. We will also characterize the surface of the autoreactive T cells and the molecules they secrete
Project start date: 2010-04-01
Project end date: 2012-12-31
Budget start date: 1-APR-2010
Budget end date: 31-DEC-2010
PFA/PA: PAR-09-031
1R03AR059312-01 (2010): $76500
Emanual M Maverakis
University Of California Davis
Project start date: 2011-09-30
Project end date: 2016-08-31