A greater understanding of the role of mast cells in innate and acquired immunity has been conducted through the evaluation, characterization and treatment of patients with cutaneous and systemic mastocytosis, a clonal mast cell disorder of excessive mast cell proliferation and activation. This initiative includes interventional approaches to better manage patients with these disorders. 

There is a research agenda to investigate the genetic basis and pathogenic mechanisms of physical urticarias, both to better understand and manage these reactions and to shed light on allergic reactions in general. Urticarial manifestations are generally thought to be the result of mast cell activation and degranulation, which is supported by the finding of increased levels of serum histamine during urticarial flares. Current translational studies are focused on the further characterization of induced urticarias through genetic sequencing, expression of mast cell activating proteins, and expression of serum cytokines. This area of research includes the evaluation of patients with autoinflammatory disorders and their genetic and phenotypic overlap with atopic diseases.

An additional area of research focuses on the utility of impulse oscillometry, a non-invasive, and non-effort dependent technology that measures airway resistance and reactance in patients with asthma and other pulmonary disorders.

Watch a video on the importance of healthy volunteers in clinical studies.

Dr. Komarow obtained his M.D. from Sackler School of Medicine in Ramat Aviv, Israel, and completed his pediatric residency at MetroHealth Medical Center/Case Western Reserve Medical Center in Cleveland, OH. Dr. Komarow completed his Allergy and Immunology Fellowship at the National Institutes of Health in 2001 and was a Research Fellow in the Genetics and Genomics Branch of the National Institute of Arthritis, Musculoskeletal and Skin Diseases until 2005, when he joined the Laboratory of Allergic Diseases as a Staff clinician. In 2018 he was appointed as an Associate Research Physician in the Mast Cell Biology Section. Dr. Komarow is a Fellow of the American Academy of Allergy, Asthma, and Immunology.

Memberships

• American Academy of Pediatrics
• American College of Allergy, Asthma, and Immunology
• American Academy of Allergy, Asthma, and Immunology

Meyer J, Gorbach AM, Liu WM, Medic N, Young M, Nelson C, Arceo S, Desai A, Metcalfe DD, Komarow HD. Mast cell dependent vascular changes associated with an acute response to cold immersion in primary contact urticaria. PLoS One. 2013;8(2):e56773.

Komarow HD, Arceo S, Young M, Nelson C, Metcalfe DD. Dissociation between history and challenge in patients with physical urticaria. J Allergy Clin Immunol Pract. 2014;2(6):786-90.

Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, Eisch AR, Long RD, Lee CC, Satorius CL, Pakstis AJ, Olivera A, Mullikin JC, Chouery E, Megarbane A, Medlej-Hashim M, Kidd KK, Kastner DL, Metcalfe DD, Komarow HD. Vibratory Urticaria Associated with a Missense Variant in ADGRE2. N Engl J Med. 2016;374(7):656-63.

Kulinski JM, Eisch R, Young ML, Rampertaap S, Stoddard J, Monsale J, Romito K, Lyons JJ, Rosenzweig SD, Metcalfe DD, Komarow HD. Skewed Lymphocyte Subpopulations and Associated Phenotypes in Patients with Mastocytosis. J Allergy Clin Immunol Pract. 2020;8(1):292-301 e2.

Komarow HD, Brenchley JM, Eisch AR, Young ML, Scott LM, Kulinski JM, Heller T, Bai Y, Metcalfe DD. A study of microbial translocation markers in mastocytosis. Clin Exp Allergy. 2021;51(2):369-72.

Makovoz A, Wang J, Oshegbo G, Park YH, Lyons JJ, Eisch AR, Scott LM, Reynolds JC, Ortega-Villa AM, Metcalfe DD, Komarow HD. Assessment of Osteoporosis and Fracture Risk in Mastocytosis Within a North American Cohort. J Allergy Clin Immunol Pract. 2021.

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Research on anaphylaxis focuses on improving management and coordinating clinical studies with basic research on the responsiveness of human mast cells.

The pediatric mastocytosis studies evaluate children with systemic mastocytosis to determine the natural history and pathogenesis of the disease, as well as parameters associated with increased morbidity.

Dr. Carter received her M.D. from Tulane University Medical School and completed her pediatric residency training at Emory University in Atlanta. She started her career in general pediatrics in an inner-city clinic. Dr. Carter was an assistant professor on the clinical faculty at Emory University for 12 years, with the final 5 years including clinical research in pediatric allergic diseases. She completed her allergy/immunology fellowship at the National Institutes of Health in 2001 and recently joined the Laboratory of Allergic Diseases as a staff physician.

Memberships

• American Academy of Pediatrics
• American Academy of Allergy, Asthma & Immunology
• National Medical Association

Carter MC, Metcalfe DD, Komarow HD. Mastocytosis. Immunol Allergy Clin North Am. 2014 Feb;34(1):181-96.

Valent P, Akin C, Arock M, Brockow K, Butterfield J, Carter M, Castells M, Escribano L, Hartmann K, Lieberman P, Nedoszytkok B, Orfaol A, Schwartz L, Sotlar K, Spera W, Triggianio M, Valenta R, Horny HP, Metcalfe D. Definitions, criteria, and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-25.

Lee YN, Brandal S, Noel P, Wentzel E, Mendell JT, McDevitt MA, Kapur R, Carter M, Metcalfe DD, Takemoto CM. KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation. Blood. 2011 Mar 31;117(13):3629-40.

Wilson TM, Maric I, Simakova O, Bai Y, Chan EC, Olivares N, Carter M, Maric D, Robyn J, Metcalfe DD. Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis. Haematologica. 2011 Mar;96(3):459-63.

Uzzaman A, Maric I, Noel P, Kettelhut BV, Metcalfe DD, Carter MC. Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology. Pediatr Blood Cancer. 2009 Oct;53(4):629-34.

Carter MC, Uzzaman A, Scott LM, Metcalfe DD, Quezado Z. Pediatric mastocytosis: routine anesthetic management for a complex disease. Anesth Analg. 2008 Aug;107(2):422-7.

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The prevalence of severe allergic disease is on the rise globally; consequently, severe systemic allergic inflammation and reactions are also becoming far more frequent, representing a major public health burden causing morbidity for patients, distress for families, and substantial costs for the healthcare system. We seek to develop methods and strategies to identify individuals at with or at high risk of developing severe allergic inflammation and anaphylaxis in order to identify specific pathways leading to these phenotypes and enable the development of new therapies that can successfully limit and/or prevent these potentially devastating consequences.

Dr. O'Connell received his Ph.D. in development origins of health and disease (cell and molecular biology) from the University of Southampton School of Medicine in the United Kingdom, in collaboration with the University of Pennsylvania. He obtained postdoctoral training in the areas of Wnt5a-mediated progression of metastatic melanoma at the National Institute on Aging from 2006 to 2011. Prior to joining the Laboratory of Allergic Diseases in 2014, Dr. O'Connell was a staff scientist at the Wistar Institute, Philadelphia, from 2011 to 2014, where he investigated mechanisms of drug resistance in cancer. Dr. O’Connell joined the Laboratory of Allergic Diseases from the Wistar Institute in 2015. Working in the Genetics and Pathology of Allergy Section, he has endothelial cell-driven mechanisms promoting atopy. He joined the Translational Allergic Immunopathology Unit in 2019 bringing with him expertise in molecular biology and cancer and is leading efforts to understand how inherited and acquired genetic variation in endothelial and myeloid cells can promote severe allergic reactions and myeloproliferation.

Desai, A., Sowerwine, K., Liu, Y., Lawrence, M.G., O’Connell, M.P., Chovanec, J., Hsu, A.P., Boris, L., Jones, N., Zerbe, C., Wisch, L., Maric, I., Lee, R.C., Gilfillan, A., Stone, K.D., Milner, J.D., Holland, S.M., Metcalfe, D.D., Lyons, J.J. GATA2-deficient mast cells limit type I hypersensitivity reactions in humans. J Allergy Clin Immunol. 2019 May 15.

Lyons, J.J., Liu, Y., Ma, C., Yu, X., O'Connell, M.P., Lawrence, M., Zhang, Y., Karpe, K., Zhao, M., Siegel, A., Stone, K.D., Nelson, C., Jones, N., Dimaggio, T., Darnell, D., Mendoza-Caamal, E., Orozco, L., Hughes, J., McElwee, J., Hohman, R., Frischmeyer-Guerrerio, P., Rothenberg, M., Freeman, A., Holland, S., and Milner, J.D. ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans. J Exp Med. 2017 Mar 6.

Lyons, J.J., Yu, X., Hughes, J.D., Le, Q.T., Jamil, A., Bai, Y., Ho, N., Zhao, M., Liu, Y., O'Connell, M.P., Trivedi, N.N., Nelson, C., DiMaggio, T., Jones, N., Matthews, H., Lewis, K.L., Oler, A.J., Carlson, R.J., Arkwright, P.D., Hong, C., Agama, S., Wilson, T.M., Tucker, S., Zhang, Y., McElwee, J.J., Pao, M., Glover, S.C., Rothenberg, M.E., Hohman, R.J., Stone, K.D., Caughey, G.H., Heller, T., Metcalfe, D.D., Biesecker, L.G., Schwartz, L.B., Milner, J.D. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016 Dec.

Kaur, A., Webster, M.R., Marchbank, K., Behera, R., Ndoye, A., Kugell III, C.H., Dang, V.M., Appleton, J., O’Connell, M.P., Cheng, P., Valiga, A.A., Morissette, R., McDonnell, N.B., Ferrucci, L., Kossenkov, A.V., Meeth, K., Tang, H., Yin, X., Wood III, W.H., Lehrmann, E., Becker, K.G., Flaherty, K.T., Frederick, D.T., Wargo, J.A., Cooper, Z.A., Tetzlaff, M.T., Hudgens, C., Aird, K.M., Zhang, R., Xu, X., Liu, Q., Bartlett, E., Karakousis, G., Eroglu, Z., Lo, R.S., Chan, M., Menzies, A.M., Long, G.V., Johnson, D.B., Sosman, J., Schilling, B., Schadendorf, D., Speicher, D.W., Bosenberg, M., Ribas, A., and Weeraratna, A.T. sFRP2 in the aged microenvironment drives melanoma metastasis and resistance to targeted therapy. Nature. 2016 Apr 14.

O’Connell, M.P.*, Hox, V.*, Lyons, J.J., Sackstein, P., Dimaggio, T., Jones, N., Nelson, C., Boehm, M., Holland, S.M., Freeman, A.F., Tweardy, D.J., Olivera, A., Metcalfe, D.D., Milner, J.D. Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol. 2016 Jul;138(1):187-99. doi: 10.1016/j.jaci.2015.11.024. * Co-first author

O’Connell M.P., Marchbank K., Webster M.R., Valiga A., Kaur A.A., Vultur A.M., Li L., Herlyn M., Villanueva J., Liu Q., Yin X., Widura S., Nelson J., Ruiz N., Camilli T.C., Indig F.E., Flaherty K.T, Wargo J.A., Frederick D.T.,. Cooper Z.A., Nair S., Amaravadi R.K., Schuchter L.M., Karakousis G., Xu W., Xu X., Weeraratna A.T. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Discov. 2013 Dec;3(12):1378-93.

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