Major Areas of Research
- The study of mast cell biology and the identification and characterization of receptors, signaling pathways and mediators contributing to mast cell-related pathology.
Mast cells are tissue resident cells of the innate immune system that contribute to immune regulation and are important for host defense against parasites and venoms. Mast cells also play a significant role in pathologic conditions such as allergy and asthma; and dysregulation of mast cell growth in patients with mastocytosis can result in numerous clinical manifestations. Mast cells respond to a number of signals, including allergens, by releasing substances that cause both immediate induction and late-phase regulation of inflammatory responses. The identification and characterization of the cues in the tissue environment that regulate mast cell activation, the intracellular signaling pathways subsequently initiated, and the soluble mediators and extracellular vesicles consequently released by mast cells, are key to the understanding of the underlying causes of allergic inflammation and mast cell-related diseases. In addition, a deeper knowledge of these processes is critical for the design of cutting edge therapeutic approaches.
Our studies have shed light on previously unrecognized pathways mediating allergic stimulation of mast cells and pathways that drive dysregulated mast cell proliferation. In addition, the finding of small extracellular vesicles released by neoplastic mast cells have opened new avenues for investigating the influence of mast cells in tissues and how they may affect pathology.
Dr. Olivera received a Ph.D. in Biochemistry from the Universidad Complutense of Madrid. She trained as a postdoctoral fellow in the laboratory of Dr. Sarah Spiegel in the Department of Biochemistry and Molecular Biology at Georgetown University, where she later became a Research Assistant Professor. There, she made important contributions to the understanding of sphingolipid breakdown products (ceramide, sphingosine, and sphingosine-1-phosphate) and their role in various biological functions. In 2003, she became a Staff Scientist in the laboratory of Dr. Juan Rivera in the Laboratory of Molecular Immunology of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). During this time, she studied signaling networks regulating mast cell activation and identified sphingosine-1-phosphate and its receptors as critical mediators in IgE-mediated mast cell activation and in allergic hypersensitivity reactions. In 2013, Dr. Olivera joined the laboratory of Dr. Dean Metcalfe, in the Mast Cell Biology Section of the Laboratory of Allergic Diseases (National Institute of Allergy and Infectious Diseases, NIAID) as a Staff Scientist and was awarded the title of Associate Scientist in 2017. She continues in her efforts to understand the regulation of mast cell responses and the impact of mast cell-derived products in inflammation and disease.
Naranjo, A.N, G. Bandara, Y. Bai, M.G. Smelkinson, A. Tobío, H.D. Komarow, S.E. Boyden, D.L. Kastner, D.D. Metcalfe, A. Olivera. 2020. Critical signaling events in the mechanoactivation of human mast cells through p.C492Y-ADGRE2. J Invest. Dermatol. doi: 10.1016/j.jid.2020.03.936 [Epub ahead of print].PMID: 32222457.
Tobio, A., G. Bandara, D.A.Morris, D-K. Kim, M.P. O'Connell, H.D. Komarow, M.C. Carter, D. Smrz, D.D. Metcalfe* and A. Olivera*. 2020. Oncogenic D816V-KIT signaling in mast cells causes persistent IL-6 production. * equal contributors. Haematologica. 105 (1):124-135. doi:10.3324/haematol.2018.212126. PMID: 30948489.
Kim, D-K., Y-E. Cho, H. Komarow, G. Bandara, B-J. Song, A. Olivera*, and D.D. Metcalfe*. 2018. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells and elicit their activation. *co-senior authors. Proc Natl Acad Sci USA. 115 (45) E10692-E10701. PMID:30352845.
Bandara, G*., R. Muñoz-Cano*, A. Tobio*, Y. Yin, H. Komarow, A. Desai, D.D Metcalfe and A. Olivera. 2018. Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells with D816V-KIT. * equal contributors. Front. Immunol. 9: 631doi: 10.3389/fimmu.2018.00631. eCollection 2018. PMID:29643855.
Kim, D-K, M.A. Beaven, D.D. Metcalfe, and A. Olivera. 2017. Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells. J. Allergy Clin Immunol. pii: S0091-6749(17)31579-8. doi: 10.1016/j.jaci.2017.08.030. PMID: 29031599.
Olivera, A., M. A. Beaven and D.D. Metcalfe. Mast cells signal their importance in health and disease. 2018. J. Allergy Clin. Immunol. pii: S0091-6749(18)30225-2. doi: 10.1016/j.jaci.2018.01.034. PMID: 29454835.