Signal transduction in mast cells and basophils
- 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.
- 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).
- Modulation of cytokine gene transcription in human T cells by Human recombinant Histamine Releasing Factor.
- Mechanism of signaling initiation from the FceRI by LynA and LynB kinases; approaches include mutational analysis, live- cell FRET and mathematical modeling
- Elucidating the distinct vs. redundant roles of Lyn A and LynB kinases in FceRI signaling to secretion and integrin-mediated cell spreading
- Molecular basis of releasability in human basophils and mast cells; signaling changes contributing to hyperreleasability or hyporeleasability in human disease states such as urticaria or atopy.
- Antagonism of IgE receptor signaling in a mouse model of asthma; transgene expression in FceRI-expressing cells.
Becky M. Vonakis, Ph.D.
Assistant Professor of Medicine
Han Sun, B.S.
JHU Biomedical Engineering Student
Inquiries about postdoctoral fellowship positions should be directed to Dr.Vonakis at email@example.com. Previous experience in signal transduction, molecular biology, confocal microscopy 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 (out of 27):
Peer Reviewed Scientific Articles:
1. 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).
2. 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).
3. Wofsy, C.*, Vonakis, B.M.*, Metzger, H. And Goldstein, B. One Lyn is sufficient to initiate phosphorylation of aggregated FceRI, Proc. Natl. Acad. Sci. (USA), 96, 8615-8620, (1999). *Equal authors.
4. 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).
5. 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).
6. 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).
7. 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 (Fc?RI), J. Immunol., 175:4543-4554 (2005).
8. Vonakis, B.M., Vasagar, K., Gibbons, Jr., S., Gober, L., Sterba, P.M., Chang, H., and Saini, S., Basophil Fc?RI histamine release parallels expression of SH2-containing inositol phosphatases in chronic idiopathic urticaria, J. Allergy Clin. Immunol. 119:441-448 (2007).
9. Vonakis, B.M. and Saini, S.S. Syk-deficient Basophils from Donors with Chronic Idiopathic Urticaria Exhibit a Spectrum of Releasability, J. Allergy Clin. Immunol. 121:262-264 (2008).
10. Vonakis, B.M., MacGlashan, Jr., D.W., Vilariño, N., Langdon, J.M., Scott, R.S., and MacDonald, S.M., Distinct Characteristics of Signal Transduction Events by Histamine Releasing Factor/Translationally Controlled Tumor Protein (HRF/TCTP)-Induced Priming and Activation of Human Basophils, Blood, 111:1789-1796 (2008).
11. Lee, M-G., Dong, X., Liu, Q., Patel, K.N., Choi, O.H., Vonakis, B., and Undem, B.J. Agonists of the Mas Related Gene (Mrgs) orphan receptors as Novel Mediators of Mast Cell-Sensory Nerve Interactions, J. Immunology, 180: 2251 – 2255 (2008).
12. Langdon, J.M., Schroeder, J., Vonakis, B.M., Bieneman, A., Chichester, K., and MacDonald, S. Histamine Releasing Factor/Translationally Controlled Tumor Protein (HRF/TCTP) Induced Histamine Release is Enhanced with SHIP-1 Knockdown in Cultured Human Mast Cell and Basophil Models, J. Leukoc. Biol., (in press, 2008).
13. Saini, S.S., Paterniti, M., Vasagar, K., Gibbons, Jr., S., Sterba, P.M., and Vonakis, B.M., Cultured Mast Cells from Chronic Idiopathic Urticaria Patients Spontaneously Degranulate Upon IgE Sensitization: Relationship to Expression of Syk and SHIP-2, Clin. Immunol., (under revision, 2008).
14. Killedar, S.J., Sun, H., Tano, J-Y., Gibbons, Jr., S.P., Chang, H., Lin, E., and Vonakis, B.M., Distinct Roles for LynA and LynB Kinases in Antigen-induced MAP Kinase Activation and Mast Cell Spreading (in preparation, 2008).
1. Vonakis, B.M., and Vanderhoek, J.Y., Role of calcium in the regulation of mammalian lipoxygenases, in “Cell Calcium Metabolism”, G. Fiskum, Ed., Plenum Press Inc., New York, pp. 387-396, (1989).
2. Metzger, H., Chen, H., Goldstein, B., Haleem-Smith, H., Inman, J.K., Peirce, M., Torigoe, C., Vonakis, B., and Wofsy, C. Signal transduction by Fc?RI: Analysis of the early molecular events. Allergology International 48, 161 169, (1999).
3. 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 (16-18), 1323-1327 (2002).
4. Vonakis, B.M., and Saini, S.S., Basophils and mast cells in chronic idiopathic urticaria. Curr. Allergy Asthma Rep. 5 (4): 270-6 (2005).
5. Vonakis, B.M. and Saini, S.S, New concepts in chronic urticaria. Curr. Opin. Immunol. (in press, 2008).
Becky Vonakis, Di Chen
|Mike McLane, Jean-Yves Tano, Becky Vonakis|
|Becky Vonakis, Jill Brederson, Smruti Killedar|
Last Updated: 11/3/08