Major Areas of Research
- Identification of mutations and polymorphisms in human disease that affect the mast cell compartment
- Characterization of key signaling pathways in human mast cells that control mast cell responses
- Application of this information to the diagnosis and treatment of anaphylaxis and other allergic and immunologic diseases
The mast cell is the focus of the Mast Cell Biology Section (MCBS) research effort. This multifunctional inflammatory cell is involved in both innate and acquired immunity and plays a central role in the induction of allergic inflammation. An integrated program investigating mast cell biology includes studies into the growth and differentiation of mast cells, mast-cell signal transduction, and the products generated by mast cells that lead to disease. The MCBS program emphasizes basic research that may be translated into the clinic, where protocols include studies on the pathogenesis of urticaria, anaphylaxis, and clonal mast cell disorders. Research efforts have contributed to the identification of mutations in mast cell disease, understanding signaling through KIT and the high affinity IgE receptors, and how alterations in the control of mast cell mediator production affect human disease.
Dr. Metcalfe received his M.D. at the University of Tennessee and an M.S. in microbiology at the University of Michigan, where he also did a residency in internal medicine. Dr. Metcalfe then trained in allergy and immunology during a fellowship at NIAID, followed by training in rheumatology while a fellow in immunology at the Robert Brigham Hospital in Boston. In 1995, he was appointed as the first chief of the newly created Laboratory of Allergic Diseases at NIAID. He is a past president of the American Academy of Allergy, Asthma, and Immunology, and a past chair of the American Board of Allergy and Immunology. Dr. Metcalfe is a Fellow of the American Academy of Allergy, Asthma, and Immunology and a member of the Association of American Physicians, Collegium Internationale Allergologicum, and American Clinical and Climatological Association.
Dean Metcalfe, M.D., Section Chief
Melody Carter, M.D., Staff Clinician
Ana Olivera, Ph.D., Staff Scientist
Geethani Bandara, Ph.D., Biologist
Yun Bai, M.S., Biologist
Yuzhi Yin, M.D., Ph.D., Biologist
Araceli Tobio, Ph.D., Visiting Fellow
Do-Kyun Kim, Ph.D., Visiting Fellow
Joseph Kulinski, Ph.D., Postdoctoral Fellow
Andrea Naranjo, Ph.D., Postdoctoral Fellow
Arnold Kirshenbaum, M.D., Special Volunteer
Linda Scott, C.R.N.P. (Nurse Practitioner)
Bandara G, Beaven MA, Olivera A, Gilfillan AM, Metcalfe DD. Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol. 2015 Aug 8. Epub ahead of print.
Carter MC, Clayton ST, Komarow HD, Brittain EH, Scott LM, Cantave D, Gaskins DM, Maric I, Metcalfe DD. Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis. J Allergy Clin Immunol. 2015 Jun 1. Epub ahead of print.
Cruse G, Beaven MA, Music SC, Bradding P, Gilfillan AM, Metcalfe DD. The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling. Mol Biol Cell. 2015 May 1;26(9):1711-27.
Hox V, Desai A, Bandara G, Gilfillan AM, Metcalfe DD*, Olivera A*. Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production. J Allergy Clin Immunol. 2015 Mar;135(3):729-36.e5. *Authors contributed equally.
Cruse G, Beaven MA, Bradding P, Gilfillan AM, Metcalfe DD. A truncated splice-variant of FceRIB is critical for microtubule formation and degranulation in mast cells. Immunity. 2013 May 23;38(5):906-17.
Medic M, Desai A, Olivera A, Rivera J, Birnbaumer L, Abramovitz J, Beaven MA, Gilfillan AM, Metcalfe DD. Knockout of the Trpc1gene reveals that TRPC1 can promote recovery from anaphylaxis by negatively regulating mast-cell TNF-a production. Cell Calcium. 2013 May-Jun;53(5-6):315-26.