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John J. O'Shea is an American physician and immunologist.
| This article has multiple issues. Please help improve it or discuss these issues on the talk page . (Learn how and when to remove these template messages)
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John J. O'Shea is an American physician and immunologist.
O'Shea was born in Clason Point in the Bronx, New York. He graduated Phi Beta Kappa with a Bachelor of Science degree from St. Lawrence University and a Doctor of Medicine degree from the University of Cincinnati. He then served as an intern and resident in internal medicine at the State University of New York Upstate Medical University in Syracuse, New York.
He came to the National Institutes of Health (NIH) in 1981 for subspecialty training in allergy and immunology in the National Institute of Allergy and Infectious Diseases. He did additional postdoctoral work in the Cell Biology and Metabolism Branch in the National Institute of Child Health and Human Development. O'Shea is board certified in internal medicine and allergy and immunology.
He started his own group in the National Cancer Institute in 1989, and then moved to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in 1994 as chief of the Lymphocyte Cell Biology Section of the Arthritis and Rheumatism Branch. He was appointed chief of the Molecular Immunology and Inflammation Branch in 2002, and became scientific director and director of the NIAMS Intramural Research Program in 2005. O'Shea also served as acting director of the NIH Center for Regenerative Medicine from 2009 to 2011. O'Shea is also an adjunct professor in the Department of Pathology at the University of Pennsylvania.
Molecular Immunology and Inflammation Branch (MIIB)
The MIIB conducts basic and clinical investigations on the molecular mechanisms underlying immune and inflammatory responses in rheumatic and autoimmune diseases. A major focus of the Branch is the study of receptor-mediated signal transduction and how these events link to the regulation of genes involved in inflammatory responses. The Branch comprises one section:
Lymphocyte Cell Biology Section
Conducts research into the molecular basis of cytokine action to define the mechanisms by which these mediators regulate processes such as development, differentiation, memory, tolerance and homeostasis in immune cells. The section also studies patients with primary immunodeficiency and autoinflammatory syndromes.
His area of scientific interest is cytokine signal transduction, dissecting the role of Jaks and Stats family transcription in immunoregulation. O'Shea and his colleagues cloned the tyrosine kinase, Jak3, and demonstrated its role in pathogenesis of severe combined immunodeficiency. O'Shea and colleagues at the NIH identified the role of Stat3 in regulating T cell cytokine production in Job's syndrome. More recently, O'Shea's laboratory has employed deep sequencing to understand the epigenetic regulation of T cell differentiation and the role of STATs in these processes.
O'Shea was awarded two US Patents related to Janus Family Kinases and identification of immune modulators (7,070,972, and 7,488,808). O'Shea collaborated with colleagues at Pfizer including Paul Changelian to develop the Janus kinase inhibitor tofacitinib. Currently there are nine Janus kinase inhibitors approved by various agencies.
O'Shea has authored more than 370 articles.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis.
In molecular biology, CD4 is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene.
FOXP3, also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues.
Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK), it is important for the activation of the T-cell receptor signaling in both naive T cells and effector T cells. The role of the Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the role of the lck varies among the memory T cells subsets. It seems that in mice, in the effector memory T cells (TEM) population, more than 50% of lck is present in a constitutively active conformation, whereas, only less than 20% of lck is present as active form of lck. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.
Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear.
In immunology, a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). Any naive T cell is considered immature and, unlike activated or memory T cells, has not encountered its cognate antigen within the periphery. After this encounter, the naive T cell is considered a mature T cell.
Interleukin 21 (IL-21) is a protein that in humans is encoded by the IL21 gene.
Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.
Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.
Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.
T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been termed as Treg17 cells.
Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.
Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.
Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.
Brigitta Stockinger, FMedSci, FRS, is a molecular immunologist in the Francis Crick Institute in London. Stockinger's lab focus on understanding how certain immune cells, called T cells, develop and function as well as investigating how diet and other environmental factors can affect the way the immune system works.
In cell biology, TH9 cells are a sub-population of CD4+T cells that produce interleukin-9 (IL-9). They play a role in defense against helminth infections, in allergic responses, in autoimmunity, and tumor suppression.
Janus kinase 3 inhibitors, also called JAK3 inhibitors, are a new class of immunomodulatory agents that inhibit Janus kinase 3. They are used for the treatment of autoimmune diseases. The Janus kinases are a family of four nonreceptor tyrosine-protein kinases, JAK1, JAK2, JAK3, and TYK2. They signal via the JAK/STAT pathway, which is important in regulating the immune system. Expression of JAK3 is largely restricted to lymphocytes, while the others are ubiquitously expressed, so selective targeting of JAK3 over the other JAK isozymes is attractive as a possible treatment of autoimmune diseases.