Richard L Stevens

BIOGRAPHY

ACADEMIC POSITIONS:
• Professor, Department of Medicine, Harvard Medical School
• Principal Investigator, Rheumatology, Immunology and Allergy, Brigham And Women's Hospital

EDUCATION:
• 1970 BA Chemistry, University of Connecticut, Storrs, CT
• 1975 PhD Biochemistry, Boston University School of Medicine, Boston, MA
• 1975-1976 Research Fellow Biochemistry, Boston University Medical School, Boston, MA
• 1976-1978 Arthritis Foundation Fellow Biochemistry, Kennedy Institute of Rheumatology, London, England
• 1978-1979 Arthritis Foundation Fellow Biochemistry, National Institutes of Health, Bethesda, MD
• 1979 Research Fellow Biochemistry-Immunology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA

MEMBERSHIPS:
• 1979-1994 Society for Complex Carbohydrates, Member
• 1982-2003 American Society for Cell Biology, Member
• 1983-present American Society for Biochemistry and Molecular Biology, Member
• 1989-present American Association of Immunologists, Member
• 1994-present Collegium Internationale Allergologicum, Council Officer
• 1996-present American Association for the Advancement of Science, Member
• 2000-present American Academy, Allergy, Asthma, and Immunology, Fellow & Liaison Committee J Allergy Clin Immunol
• 2005-present Food Allergy & Anaphylaxis Network, Member
• 2010-present The Mastocytosis Society, Member

HONORS AND AWARDS:
• 1979 Back Pain Association Medal (England)
• 1980-1982 Established Investigator, Kroc Foundation
• 1981-1982 Milton Fund Award, Harvard Medical School
• 1986-1991 Established Investigator, American Heart Association
• 2000-2001 Established Investigator, Mizutani Foundation for Glycoscience (Japan)
• 2004 Honorary Masters Degree, Harvard University
• 2010 Established Investigator and Fellow, Harvard Club of Australia

RESEARCH INTERESTS:
My research is focused on the molecular and cell biology of mast cells (MCs) and other effector cells that participate in varied inflammatory processes. In regard to the MC, these immune cells release a diverse array of biologically active molecules (including cytokines, chemokines, leukotrienes, prostaglandins, amines, proteoglycans, and proteases) when activated through their high-affinity IgE receptors. The presence of increased numbers of activated MCs in the skin of mastocytoma patients, in the bronchial airways of individuals with asthma and chronic allergies, in the skin of patients undergoing extensive fibrosis, in the intestines of helminth infected individuals, in tumors of cancer patients, and in the joints of patients afflicted with rheumatoid arthritis suggest that these effector cells play central roles in a number of inflammatory disorders. Numerous studies have suggested that MCs also play important roles in development. For example, transgenic mice that lack the mouse MC chymase mMCP-5 possess developmental defects in their eyes with variable penetrance. MCs also play important roles in innate immunity, particularly during bacteria infections. In this regard, mMCP-6 and its human ortholog tryptase beta I regulate the extravasation of neutrophils into bacteria-infected tissues.

Mammalian MCs are a heterogeneous family of hematopoietic cells whose ultimate phenotype is dependent on the tissue microenvironment the mature cell eventually resides. In vitro and molecular biology approaches have been developed to identify the factors that regulate the differentiation and phenotypic properties of MCs. In this regard, a new cation-dependent, MC-restricted guanine exchange factor/phorbol ester receptor (designated as RasGRP4) has been identified that appears to be essential for the development of mature MCs. This signaling protein controls what proteases and eicosanoids MCs eventually express. By varying the culture conditions, we and others have been able to induce bone marrow progenitor cells to differentiate and mature into populations of MCs that have varied phenotypes. We have identified a number of novel human and mouse MC-specific genes; we are now investigating why and how these genes and their transcripts are regulated as the MC's microenvironment is altered. Cis-acting elements and trans-acting DNA-binding proteins that regulate transcription of these genes and RNA-binding proteins that regulate the stability of their transcripts are being identified. Transgenic mice have been created that differ substantially in the number of MCs that they have in their tissues. A transgenic/adoptive transfer approach also has been developed in order to address the role of varied MC-derived factors. Recombinant MC-derived proteases have been generated in order to evaluate their physiologic function. What happens to T cells, epithelial cells, endothelial cells, neurons, fibroblasts, chondrocytes, and smooth muscle cells when they interact with MCs and their granule proteases also are being investigated. The consequences of HIV-1 infection of human MCs and their progenitors is another area of investigation.

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