Major Areas of Research
- The study of mast cell biology and the identification and characterization of mediators, receptors and signaling pathways contributing to mast cell-related disorders.
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 environmental cues, including allergens, by releasing substances that cause both immediate induction and late-phase regulation of inflammatory responses. The identification and characterization of the environmental cues that activate mast cells, the intracellular signaling pathways subsequently initiated, and the substances and 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 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 was appointed 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 identified sphingosine-1-phosphate and its receptors as critical mediators in mast-cell activation and allergic hypersensitivity. Dr. Olivera joined the Mast Cell Biology Section of the LAD (NIAID) in 2013 as a staff scientist and became an 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.
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
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
Kulinski, J.M., R.L. Proia, E. Larson, D.D. Metcalfe and A. Olivera. 2018. S1P4 regulates passive systemic anaphylaxis in mice but is dispensable for canonical IgE-mediated responses in mast cells. Int J Mol Sci 19(5), 1279; doi:10.3390/ijms19051279. PMID: 29693558.
Hox,V., Desai, A., Bandara, G., Gilfillan, A., Metcalfe, D.D* and Olivera, A*. Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production. * Equal contributors. J. Allergy Clin. Immunol. 2015:135: 729-736.
Muñoz-Cano R, Pascal M, Bartra J, Picado C, Valero A, Kim DK, Brooks S, Ombrello M, Metcalfe DD, Rivera J, Olivera A. 2015. Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug-dependent from nonsteroidal anti-inflammatory drug-independent food-induced anaphylaxis. J Allergy Clin Immunol. 2015: doi: 10.1016/j.jaci.2015.05.042. [Epub ahead of print]
Olivera A, Eisner C, Kitamura Y, Dillahunt S, Allende L, Tuymetova G, Watford W, Meylan F, Diesner SC, Li L, Schnermann J, Proia RL, Rivera J. Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice. J Clin Invest. 2010 May;120(5):1429-40.
Olivera A, Mizugishi K, Tikhonova A, Ciaccia L, Odom S, Proia RL, Rivera J. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity. 2007 Mar;26(3):287-97.
Olivera A, Spiegel S. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature. 1993 Oct 7;365(6446):557-60.