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Signal transduction in mast cells and basophils
Interests:
- Signal transduction in immune/inflammatory cells with a particular emphasis on basophils and mast cells.
- Development of inhibitors of signal transduction for the treatment of allergic and skin diseases.
- Development of techniques for the introduction of proteins and gene expression in terminally differentiated cells.
Past research:
- Characterization of a receptor for 15-HETE ; HETE-mediated regulation of lipoxygenase enzymes.
- Mapping of the sites of interaction between Lyn kinase and the high affinity receptor for IgE (FceRI); mechanism of signaling initiation.
- Modulation of cytokine gene transcription in human T cells by Human recombinant Histamine Releasing Factor.
Current research:
- Modulation of FceRI signal transduction by transfected Lyn unique domain . Interplay between Lyn and Fyn kinase in regulating secretion of allergic mediators from mast cells.
- Role of SHIP-1 phosphatase in regulating releasability in human basophils.
- Signaling changes occurring in basophils and cultured mast cells from donors with Chronic Idiopathic Urticaria and Cold-induced Urticaria. Role of basophils and mast cells in urticarial disease pathogenesis.
Laboratory:
Becky M. Vonakis, Ph.D.
Assistant Professor of Medicine
Smruti Killedar, Ph.D.
Post-doctoral Fellow
Hyeyoun Chang, B.A.
Senior Laboratory Technician
Positions available:
Inquiries about postdoctoral fellowship positions should be directed to Dr. Vonakis at mailto:bvonaki@jhmi.edu?subject=research position. Previous experience in signal transduction, molecular biology and/or transgenic mouse models would be helpful. If interested, please send your CV, a statement of research interests and availability.
Undergraduate students interested in a laboratory research position should email Dr. Vonakis. Generally one or two positions are available each semester for highly motivated students who are willing to learn. Students must be able to work at least one full day and a second half-day per week. They must have taken courses in cell biology and/or molecular biology. Coursework in immunology and previous research experience would be helpful.
Selected publications:
1. Vonakis, B.M., and Vanderhoek, J.Y., A calcium-independent 5-lipoxygenase system in mast basophil PT-18 cells, Biochim. Biophys. Acta., 1045,142-146, (1990).
2. Vonakis, B.M., and Vanderhoek, J.Y., 15-HETE receptors: involvement in the 15-HETE-induced stimulation of the cryptic 5-lipoxygenase in PT-18 mast/basophil cells, J. Biol. Chem. 267(33), 23625-23631, (1992).
3. Vonakis, B.M., and Vanderhoek, J.Y., The simultaneous determination of hydroxyeicosanoid (HETE) binding to cells and its cellular metabolism, J. Lipid Res. 34(5), 853-858, (1993).
4. Vonakis, B.M., Chen, H., Haleem-Smith, H., and Metzger, H. The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE, J. Biol. Chem. 272(38), 24072-24080, (1997).
5. Wofsy, C.*, Vonakis, B.M.*, Metzger, H. And Goldstein, B. One Lyn is sufficient to initiate phosphorylation of aggregated Fc?RI, Proc. Natl. Acad. Sci. (USA), 96, 8615-8620, (1999). *Equal authors
6. Vonakis, B.M., Haleem-Smith, H., Benjamin, P. S. and Metzger, H. Interaction between the unphosphorylated receptor with high affinity for IgE and Lyn kinase, J. Biol. Chem., 276, 1041-1050, (2001).
7. Vonakis, B.M., Gibbons, S.P., Jr., Sora, R., Langdon, J.M., and MacDonald, S.M., Src homology 2 domain-containing inositol 5' phosphatase is negatively associated with histamine release to human recombinant histamine-releasing factor in human basophils, J. Allergy Clin. Immunol., 108, 822-831 (2001).
8. MacDonald, S.M., and Vonakis, B.M., Association of the Src homology 2 domain-containing inositol 5’ phosphatase (SHIP) to releasability in human basophils. Mol. Immunol. 38, 1323-1327, (2002).
9. Vonakis, B.M., Sora, R., Langdon, J.M., Casolaro, V., and MacDonald, S.M., Inhibition of Cytokine Gene Transcription by the Human recombinant Histamine Releasing Factor (HrHRF) in Human T Lymphocytes, J. Immunol., 171(7):3742-50 (2003).
10. Langdon, J.M., Vonakis, B.M., and MacDonald, S.M. Identification of the Interaction between the Human Recombinant Histamine Releasing Factor/Translationally Controlled Tumor protein and Elongation Factor 1-delta, Biochim. Biophys. Acta , 1688:232-236 (2004).
11. Vonakis, B.M., Gibbons, S.P. Jr., Rotté, M.J., Brothers, E.A., Kim , S.C., Chichester, K., and MacDonald, S.M., Regulation of RBL-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FceRI), J. Immunol., (2005, in press).
14. MacDonald, S.M., and Vonakis, B.M., Preface to “Emerging Therapies for Allergic Disease” in Immunology and Allergy Clinics of North America, Vol. 24, Number 4; MacDonald, S.M., and Vonakis, B.M., Eds., Elsevier nc., Philadelphia, PA, pp. xi-xiii, (2004).
15. Vonakis, B.M., and Saini, S.S., Basophils and mast cells in chronic idiopathic urticaria. Curr. Allergy Asthma Rep. 5 (4): 270-6 (2005).
Last Updated: 7/8/05
