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 with Dr. K. Frank Austen 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, a position he held from 1995 to 2017. 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. He is the recipient of numerous awards including the Outstanding Commendation Medal, the Service Medal, and the Meritorious Service Medal from the USPHS; the AAAAI Distinguished Scientist Award; the World Allergy Organization Scientific Achievement Award; and the AAAAI Mentorship Award in recognition for a lifetime of service as an allergy/immunology mentor for students, residents, post-doctoral fellows and faculty.
Dean D. Metcalfe, Senior Investigator (Chief)
Ana Olivera, Ph.D., Staff Scientist
Melody Carter, M.D., Staff Clinician
Hirsh Komarow, M.D., Staff Clinician
Hyejeong Bolan, Senior Research Nurse (Nurse Study Coordinator)
Linda Scott, Advanced Practice Nurse (Nurse Practitioner)
Andrea (Robin) Eisch, Nurse Specialist (Nurse Study Coordinator)
Yun Bai, Biologist
Geethani Bandara, Biologist
Yuzhi Yin, Biologist
Do-Kyun Kim, Visiting Fellow
Andrea Naranjo Erazo, Post-Doctoral IRTA
Joseph Kulinski, Post-Doctoral IRTA
Guido Falduto, Visiting Fellow
Hanna Abuhay, Post-Baccalaureate IRTA
Amita Kashyap, Post-Baccalaureate IRTA
Arnold Kirshenbaum, Special Volunteer
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.
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, Yin Y, Fukuyama T, Desai A, Arthur GK, Bäumer W, Beaven MA, Metcalfe DD. Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy. Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14115-14120.
Carter MC, Desai A, Komarow HD, Bai Y, Clayton ST, Clark AS, Ruiz-Esteves KN, Long LM, Cantave D, Wilson TM, Scott LM, Simakova O, Jung MY, Hahn J, Maric I, Metcalfe DD. A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis. J Allergy Clin Immunol. 2018 Jan;141(1):180-188.
Kim DK, Beaven MA, Metcalfe DD, Olivera A. Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells. J Allergy Clin Immunol. 2018 Jul;142(1):195-206.
Kim DK, Cho YE, Komarow HD, Bandara G, Song BJ, Olivera A, Metcalfe DD. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their activation. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10692-E10701.