Eric Sebzda, Ph.D.

Assistant Professor

eric.sebzda@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Medical Biophysics, University of Toronto, TorontoB.Sc., Immunology, University of Toronto, Toronto
Office Address
A5211 MCN
1161 21st Ave. S
Nashville, TN 37232-2363
Research Description
A unique aspect of the immune system is its ability to transport cells great distances in a short period of time. These trafficking mechanisms dictate the efficiency of an immune response, both in terms of pathogen clearance and susceptibility to autoimmune diseases. The Sebzda laboratory studies B and T cell trafficking during immune responses. Specially, we are interested in determining how cell activation releases these lymphocytes from a homeostatic migration pattern and targets these cells to sites of inflammation. We are currently using a series of genetically modified animal models to analyze early regulatory events in cellular trafficking. The ultimate goal of this research is to identify potential therapeutic targets that enhance/inhibit lymphocyte trafficking to specific tissues and thus aid in pathogen clearance or limit autoimmune reactions, respectively.
Research Keywords
We investigate the molecular mechanisms that underpin immunological diseases including inefficient responses to pathogens, unwarranted inflammation, and autoimmunity.
Publications
Pabbisetty SK, Rabacal W, Maseda D, Cendron D, Collins PL, Hoek KL, Parekh VV, Aune TM, Sebzda E. KLF2 is a rate-limiting transcription factor that can be targeted to enhance regulatory T-cell production. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Jul 7/1/2014; 111(26): 9579-84. PMID: 24979767, PMCID: PMC4084438, PII: 1323493111, DOI: 10.1073/pnas.1323493111, ISSN: 1091-6490.

Hoek KL, Gordy LE, Collins PL, Parekh VV, Aune TM, Joyce S, Thomas JW, Van Kaer L, Sebzda E. Follicular B cell trafficking within the spleen actively restricts humoral immune responses. Immunity [print-electronic]. 2010 Aug 8/27/2010; 33(2): 254-65. PMID: 20691614, PMCID: PMC2929658, PII: S1074-7613(10)00281-5, DOI: 10.1016/j.immuni.2010.07.016, ISSN: 1097-4180.

Bertozzi CC, Schmaier AA, Mericko P, Hess PR, Zou Z, Chen M, Chen CY, Xu B, Lu MM, Zhou D, Sebzda E, Santore MT, Merianos DJ, Stadtfeld M, Flake AW, Graf T, Skoda R, Maltzman JS, Koretzky GA, Kahn ML. Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood [print-electronic]. 2010 Jul 7/29/2010; 116(4): 661-70. PMID: 20363774, PMCID: PMC3324297, PII: blood-2010-02-270876, DOI: 10.1182/blood-2010-02-270876, ISSN: 1528-0020.

Sebzda E, Zou Z, Lee JS, Wang T, Kahn ML. Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns. Nat. Immunol [print-electronic]. 2008 Mar; 9(3): 292-300. PMID: 18246069, PII: ni1565, DOI: 10.1038/ni1565, ISSN: 1529-2916.

Lee JS, Yu Q, Shin JT, Sebzda E, Bertozzi C, Chen M, Mericko P, Stadtfeld M, Zhou D, Cheng L, Graf T, MacRae CA, Lepore JJ, Lo CW, Kahn ML. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev. Cell. 2006 Dec; 11(6): 845-57. PMID: 17141159, PII: S1534-5807(06)00399-6, DOI: 10.1016/j.devcel.2006.09.006, ISSN: 1534-5807.

Sebzda E, Hibbard C, Sweeney S, Abtahian F, Bezman N, Clemens G, Maltzman JS, Cheng L, Liu F, Turner M, Tybulewicz V, Koretzky GA, Kahn ML. Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev. Cell. 2006 Sep; 11(3): 349-61. PMID: 16950126, PII: S1534-5807(06)00308-X, DOI: 10.1016/j.devcel.2006.07.007, ISSN: 1534-5807.

Abtahian F, Bezman N, Clemens R, Sebzda E, Cheng L, Shattil SJ, Kahn ML, Koretzky GA. Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol. Cell. Biol. 2006 Sep; 26(18): 6936-49. PMID: 16943434, PMCID: PMC1592869, PII: 26/18/6936, DOI: 10.1128/MCB.01040-06, ISSN: 0270-7306.

Chen H, Zou Z, Sarratt KL, Zhou D, Zhang M, Sebzda E, Hammer DA, Kahn ML. In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines. Genes Dev. 2006 Apr 4/15/2006; 20(8): 927-32. PMID: 16618804, PMCID: PMC1472300, PII: 20/8/927, DOI: 10.1101/gad.1408306, ISSN: 0890-9369.

Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, Myers EE, Huang B, Jackson DG, Ferrari VA, Tybulewicz V, Lowell CA, Lepore JJ, Koretzky GA, Kahn ML. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003 Jan 1/10/2003; 299(5604): 247-51. PMID: 12522250, PMCID: PMC2982679, PII: 299/5604/247, DOI: 10.1126/science.1079477, ISSN: 1095-9203.

Sebzda E, Bracke M, Tugal T, Hogg N, Cantrell DA. Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling. Nat. Immunol [print-electronic]. 2002 Mar; 3(3): 251-8. PMID: 11836528, PII: ni765, DOI: 10.1038/ni765, ISSN: 1529-2908.

Ohteki T, Hessel A, Bachmann MF, Zakarian A, Sebzda E, Tsao MS, McKall-Faienza K, Odermatt B, Ohashi PS. Identification of a cross-reactive self ligand in virus-mediated autoimmunity. Eur. J. Immunol. 1999 Sep; 29(9): 2886-96. PMID: 10508263, PII: 10.1002/(SICI)1521-4141(199909)29:09<2886::AID-IMMU2886>3.0.CO;2-A, DOI: 10.1002/(SICI)1521-4141(199909)29:09<2886::AID-IMMU2886>3.0.CO;2-A, ISSN: 0014-2980.

Sebzda E, Mariathasan S, Ohteki T, Jones R, Bachmann MF, Ohashi PS. Selection of the T cell repertoire. Annu. Rev. Immunol. 1999; 17: 829-74. PMID: 10358775, DOI: 10.1146/annurev.immunol.17.1.829, ISSN: 0732-0582.

Sebzda E, Choi M, Fung-Leung WP, Mak TW, Ohashi PS. Peptide-induced positive selection of TCR transgenic thymocytes in a coreceptor-independent manner. Immunity. 1997 May; 6(5): 643-53. PMID: 9175842, PII: S1074-7613(00)80352-0, ISSN: 1074-7613.

Speiser DE, Sebzda E, Ohteki T, Bachmann MF, Pfeffer K, Mak TW, Ohashi PS. Tumor necrosis factor receptor p55 mediates deletion of peripheral cytotoxic T lymphocytes in vivo. Eur. J. Immunol. 1996 Dec; 26(12): 3055-60. PMID: 8977304, DOI: 10.1002/eji.1830261235, ISSN: 0014-2980.

Bachmann MF, Sebzda E, Kündig TM, Shahinian A, Speiser DE, Mak TW, Ohashi PS. T cell responses are governed by avidity and co-stimulatory thresholds. Eur. J. Immunol. 1996 Sep; 26(9): 2017-22. PMID: 8814240, DOI: 10.1002/eji.1830260908, ISSN: 0014-2980.

Kündig TM, Shahinian A, Kawai K, Mittrücker HW, Sebzda E, Bachmann MF, Mak TW, Ohashi PS. Duration of TCR stimulation determines costimulatory requirement of T cells. Immunity. 1996 Jul; 5(1): 41-52. PMID: 8758893, PII: S1074-7613(00)80308-8, ISSN: 1074-7613.

Sebzda E, Kündig TM, Thomson CT, Aoki K, Mak SY, Mayer JP, Zamborelli T, Nathenson SG, Ohashi PS. Mature T cell reactivity altered by peptide agonist that induces positive selection. J. Exp. Med. 1996 Mar 3/1/1996; 183(3): 1093-104. PMID: 8642251, PMCID: PMC2192317, ISSN: 0022-1007.

Sebzda E, Wallace VA, Mayer J, Yeung RS, Mak TW, Ohashi PS. Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science. 1994 Mar 3/18/1994; 263(5153): 1615-8. PMID: 8128249, ISSN: 0036-8075.

Available Postdoctoral Position Details
Two postdoctoral positions are currently available in the Department of Microbiology and Immunology, at Vanderbilt University to study a unique aspect of chemokine receptor regulation in lymphocytes (Nature Immunology (2008) 9, 292-300). Studies are focused on addressing how the transcription factor, Kruppel-like factor 2 (Klf2), represses inflammatory chemokine receptor transcription while maintaining expression of homeostatic migratory receptors. As well, the laboratory is studying how aberrant naïve T cell trafficking affects the immune system, both in terms of pathogen clearance and susceptibility to autoimmune disorders. Applicants should possess a PhD or MD/PhD in Microbiology, Genetics, Immunology or a related field. Candidates applying for the Molecular Immunology position should be proficient in molecular biology techniques including protein purification, Westerns, gel-shift assays, transcription reporter assays, and RT-PCR. Candidates applying for the Cellular Immunology position should be adept at cell culture techniques, flow cytometry, and analysis of primary mouse lymphocytes including proliferation, cytokine, and cytolytic assays. Experience working with transgenic and knockout mice is an asset for both positions. The successful candidates will gain experience in a number of cutting edge molecular and cellular biological techniques. Importantly, both projects have great potential to become independent research projects that would further ambitious, motivated postdoctoral careers. Please send a curriculum vita, names of three references, and a letter describing research accomplishments and career objectives to: Dr. Eric Sebzda Vanderbilt University Department of Microbiology and Immunology 1161 21st Ave. S MCN A5211 Nashville, TN 37232