Ana Olivera, Ph.D.

Ana Olivera, Ph.D.

Credit: NIAID
Associate Scientist, Mast Cell Biology Section, Laboratory of Allergic Diseases

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.

Program Description

Mast cells are tissue resident hematopoietic cells that contribute to immune regulation and are important for host defense against parasites and venoms. Mast cells also play crucial roles in the pathogenesis of allergic diseases, and in disorders such as mastocytosis, where mast cells abnormally accumulate in different organs, and cause allergy-like symptoms, for example flushing, hives, itching, abdominal pain and anaphylaxis. 

When activated, mast cells rapidly release potent vasoactive and inflammatory substances that cause immediate allergic reactions and can lead to chronic inflammation and tissue remodeling. The identification and characterization of the signals in the tissue environment that regulate mast cell activation, the intracellular signaling pathways subsequently initiated, and the soluble mediators and extracellular vesicles released by activated 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.

Biography

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.

Selected Publications

Kim, D-K., G. Bandara, Y-E Cho,HD Komarow, DR Donahue, B Karim, MC Baek, HM Kim, D.D. Metcalfe*, A. Olivera*. 2021. Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation. Nature Commun. * senior co-authors. 12(1):2527. doi: 10.1038/s41467-021-22754-4. PMID: 33953168.

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-ADGRE2J 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 cellsJ. Allergy Clin Immunol. pii: S0091-6749(17)31579-8. doi: 10.1016/j.jaci.2017.08.030.  PMID: 29031599.

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