Education:
B.S. - Colorado State University
Ph.D. - University of Montana
Postdoctoral – Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, NIH
Research Interests:
The primary focus of the laboratory is to understand the molecular and cellular mechanisms involved in the immune response following inhalation of nanoparticles which lead to lung and cardiovascular injury. We have recently identified the activation of mast cells as a critical step in the initiation and progression of pulmonary inflammation, fibrosis and cardiovascular injury following nanoparticle exposure.
Mast cells have long been recognized for their role in the genesis of allergic inflammation and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and respiratory tract where they interface with the external environment, thereby facilitating their interaction with environmental exposures.
Current and future studies are aimed at: (I) further delineating the role of mast cells and mast cell derived products in pulmonary and cardiovascular injury following exposure to nanoparticles; (II) elucidating the role of various receptors, including scavenger receptors, which are involved in the recognition of nanoparticles by mast cells and the subsequent signaling pathways leading to mast cell activation; (III) begin to identify new strategies for the treatment of environmentally mediated diseases through therapeutic targeting mast cells.
The Brown lab is supported by:
National Institute of Environmental Health Sciences (NIEHS):
· Outstanding New Environmental Scientist Award (RO1) “Mechanisms of Mast Cell Directed Carbon Nanotube Toxicity”.
· Center for Estimating Human Health Risks from Exposure to Nanomaterials: C60, MWCNTs, and the Influence on Cardiovascular, Reproductive, and Developmental Processes (U19)
North Carolina Biotechnology Center (NCBC):
· Biotechnology Research Grant- “Mast Cells as Model for Studying Carbon Nanotube Toxicity”.
· Institutional Development Grant- “Rodent Inhalation System to Assesss Health Risks Associated with Nanoparticle Exposure”.
Selected Publications:
Chen R, Choudhary P, Schurr RN, Battacharya P, Brown JM, Ke PC. Interaction of Lipid Vesicle with Silver Nanoparticle-Serum Albumin Protein Corona. Applied Physics Letters, 2012.
Wang X*, Katwa P*, Podila R, Chen P, Ke PC, Rao AM, Walters DM, Wingard CJ, Brown JM. Multi-Walled Carbon Nanotube Instillation Impairs Pulmonary Function in C57BL/6 Mice. In Press 2011. Particle and Fibre Toxicology. *Co-First Authors
Wingard CJ, Walters DM, Cathey BL, Hilderbrand SC, Katwa P, Lin S, Ke PC, Podila R, Rao, A, Lust RM, Brown JM. Mast Cells Contribute to Alteration of Vascular Reactivity and Myocardial Ischemia/Reperfusion Injury Following Instillation of Cerium Oxide Nanoparticles. In Press 2010. Nanotoxicology.
Brown JM, Nemeth K, Kushnir-Sukhov NM, Mecalfe DD, Mezey E. Bone Marrow Stromal Cells Inhibit Mast Cell Function Via a COX2 Dependent Mechanism. In Press 2010. Clinical and Experimental Allergy.
Wang X, Reece SP, Van Scott MR, Brown JM. A Circadian Clock in Bone Marrow-Derived Mast Cells Modulates IgE-Dependent Activation In Vitro. In Press. Brain, Behavior and Immunity.
Hilderbrand SC, Murrell RN, Gibson JE, Brown JM. Marine Brevetoxin Induces IgE-Independent Mast Cell Activation. Archives of Toxicology. 2010.
Kuehn HS, Radinger M, Brown JM, Ali K, Vanhaesebroek B, Beaven MA, Metcalfe DD, Gilfillan AM. Btk-Dependent Rac Activation and Actin Rearrangement Following FcεRI Aggregration Promotes Enhanced Chemotactic Responses of Mast Cells. Journal of Cell Science. 2010
Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gorham JD, Bundoc VG, Hodges MG, Jelinek I, Madala S, Karpati S, Mezey E. Bone marrow stromal cells use TGF-{beta} to suppress allergic responses in a mouse model of ragweed-induced asthma. Proceedings of the National Academy of Sciences. 2010.
Knisz J, Banks A, McKeag L, Metcalfe DD, Rothman PB, Brown JM. Loss of SOCS7 in Mice Results in Severe Cutaneous Disease and Increased Mast Cell Activation. Clinical Immunology, 2009.
Németh K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Xuzhen H, Jelinek I, Star RA, Mezey E. Bone Marrow Stromal Cells Attenuate Sepsis via Prostaglandin E2-dependent Reprogramming of Host Macrophages to Increase their Interleukin-10 Production. Nature Medicine, 2009; 15(1):42-49.
Brown JM, Wilson TM, Metcalfe DD. The Mast Cell and Allergic Diseases: Role in Pathogenesis and Implications for Therapy. Clinical and Experimental Allergy, 2008; 38(1):4-18.
Pfau JC, Sentissi JJ, Blake DJ, Li S, Calderon-Garciduenas L, Brown JM. Asbestos Induced Autoimmunity in C57Bl/6 Mice. Journal of Immunotoxicology, 2008; 5(2):129-137.
Brown JM*, Soule BP*, Kushnir-Sukhov NM, Simone NL, Mitchell JB, Metcalfe DD. Effects of Gamma Radiation on FcεRI and Toll-Like Receptor Mediated Mast Cell Activation. Journal of Immunology, 2007; 179(6):3277-3286. *Co-First Authorship
Brown JM, Swindle EJ, Kushnir-Sukhov NM, Holian A, Metcalfe DD. Silica Directed Mast Cell Activation is Enhanced by Scavenger Receptors. American Journal of Respiratory Cell and Molecular Biology, 2007; 36:43-52.
Kushnir-Sukhov NM, Gilfillan AM, Coleman JW, Brown JM, Bruening S, Toth M, Metcalfe DD. 5-Hydroxytryptamine Induces Mast Cell Adhesion and Migration. Journal of Immunology, 2006; 177:6422-6432.
|
