A5058234244- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Platelet Disorders and Treatments
- Heparin-Induced Thrombocytopenia and Thrombosis
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Intramuscular injections and effects
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Blood disorders and treatments
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- CAR-T cell therapy research
- interferon and immune responses
- Pancreatic function and diabetes
- Chronic Lymphocytic Leukemia Research
- Autoimmune Bullous Skin Diseases
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Venous Thromboembolism Diagnosis and Management
- Advanced Proteomics Techniques and Applications
- Blood groups and transfusion
- Mast cells and histamine
Versiti Blood Center of Wisconsin
2015-2024
Medical College of Wisconsin
2006-2024
Renfe Operadora (Spain)
2013
Louisiana State University
2006
Louisiana State University Health Sciences Center New Orleans
2006
State Key Laboratory of Pharmaceutical Biotechnology
2006
Nanjing University
2006
China Pharmaceutical University
2006
St. Jude Children's Research Hospital
1993-2001
Howard Hughes Medical Institute
2000
Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the cell response; however, molecular pathways which sustains immunity remain unclear. We demonstrate that causes phenotypic switch transcription factor expression during infection characterized sustained BATF expression. Importantly, both required for optimal persistence and anti-viral effector function sufficient to rescue "unhelped"...
Abstract Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4 + T follicular helper (Tfh) cells main subset regulating autoreactive B cells. Here we report a CXCR5 PD1 Tfh CD8 whose development and function negatively modulated Stat5. These regulate germinal center cell response control autoantibody production, as deficiency Stat5 in leads to an increase cells, resulting breakdown tolerance concomitant production. share similar gene...
Phospholipase Cγ1 (PLCγ1) is an important signaling effector of T cell receptor (TCR). To investigate the role PLCγ1 in biology, we generated and examined mice with cell–specific deletion PLCγ1. We demonstrate that deficiency affects positive negative selection, significantly reduces single-positive thymocytes peripheral cells, impairs TCR-induced proliferation cytokine production, activation ERK, JNK, AP-1, NFAT, NF-κB. Importantly, development function FoxP3+ regulatory causing...
Stat5A, a member of the signal transducers and activators transcription (Stat) family, is activated upon single tyrosine phosphorylation. Although much known about activation process, mechanism by which tyrosine-phosphorylated Stat5A proteins are inactivated largely unknown. In this report, we demonstrate that down-regulation was via dephosphorylation. Using peptides derived from were able to purify protein-tyrosine phosphatase Shp-2 cell lysates. Shp-2, but not Shp-1, specifically...
G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-kappaB activation, molecular mechanism by which induced activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades lymphocytes. However, function nonlymphoid cells be determined. In this study, we demonstrated deficiency resulted defect either...
The DMP1 transcription factor induces the ARF tumor suppressor gene in mouse fibroblasts, leading to cell cycle arrest a p53-dependent manner. We disrupted sequences encoding DNA-binding domain of embryonic stem cells and derived animals lacking functional protein. DMP1-null are small at birth, males develop more slowly than their wild-type littermates. Some adult exhibit seizures and/or obstuctive uropathy, each unknown cause. growth explanted embryo fibroblasts (MEFs) is progressively...
Humans and mice lacking functional caspase-8 in T cells manifest a profound immunodeficiency syndrome due to defective cell antigen receptor (TCR)-induced NF-kappaB signaling proliferation. It is unknown how activated following stimulation, what the substrate(s) that necessary initiate cycling. We observe TCR ligation, small portion of total cellular c-FLIP(L) rapidly migrate lipid rafts where they associate an active caspase complex. Activation followed by rapid cleavage at known site. The...
Abstract The two closely related Stat5 (Stat5A and Stat5B) proteins are activated by a broad spectrum of cytokines. However, with the complication involvement Stat5A/5B in stem cell function, role development function lymphocytes, especially B cells, is not fully understood. In this study, we demonstrated that Stat5A/5B−/− fetal liver cells had severe diminution progenitors but clearly myeloid progenitors. Consistently, mutant could give rise to hemopoietic beyond pro-B lethally irradiated...
Abstract The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. PLCγ signaling pathway critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine unknown. Here we show that PLCγ1/PLCγ2 double deficiency mice blocks development at pre-pro-B stage and renders progenitors unresponsive to IL-7. inhibition IL-7-induced activation mTOR, not Stat5. activates mTOR through DAG/PKC branch, independent conventional...
Abstract Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of B cell receptor cells and FcRγ chain-containing collagen platelets. Here we report that PLCγ2 is also expressed mast monocytes/macrophages activated by cross-linking FcεR FcγR. Although PLCγ2-deficient mice have normal development numbers monocytes/macrophages, demonstrate essential for specific While mitogen-activated protein kinase activation cytokine production at mRNA levels, mutant impaired FcεR-mediated Ca2+...
Recent studies have shown that only a subset of major histocompatibility complex (MHC) class II molecules are able to present bacterial superantigens T cells, leading the suggestion class-II associated peptides may influence superantigen presentation. Here, we assessed potential role on presentation by (a) analyzing ability block peptide-specific cell responses and (b) individual promote I-Ab-expressing T2 cells quantitative defect in antigen processing. A series is described specifically...
The transcription factor Foxp3 is essential for the development of functional, natural Treg (nTreg), which plays a prominent role in self-tolerance. Suppressive Foxp3(+) cells can be generated from naïve T ex vivo, following TCR and TGF-beta1 stimulations. However, molecular contributions different arms these pathways leading to expression are not fully understood. TGF-beta1-activated Smad3 major Foxp3, since TGF-beta1-induced-Treg generation Smad3(-/-) mice markedly reduced abolished by...
Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from have a high apoptotic index, suggesting that Jak3 provides survival signals. Here we report regulates lymphopoiesis at least in part through its selective regulation Bax Bcl-2. thymocytes express elevated levels Bcl-2 relative to those wild-type littermates. Notably, up-regulation is physiologically relevant, as double-null marked increases thymocyte T-cell numbers. Rescue by loss was...
Abstract The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that expressed in lymphoid tissues. Upon stimulation or B cells, it phosphorylated and interacts with Grb2 the p85 subunit PI3K. LAX, however, not capable replacing LAT TCR signaling pathway. In this study we report upon cell activation, was up-regulated dramatically. Although disruption gene by homologous recombination had no major impact on lymphocyte development, caused...
Abstract NK cells play a central role in mediating innate immune responses. Activation of results cytotoxicity, cytokine, and chemokine secretions. In this study, we show that mice with targeted deletion phospholipase Cγ (PLCγ)2, one the key signal transducers, there are profound effects on development terminal maturation cells. Lack PLCγ2 significantly impaired ability lineage-committed precursor to acquire subset-specific Ly49 receptors thereby Overexpression isozyme, PLCγ1,...