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Bochner, Bruce S., M.D.

Bochner

BIOGRAPHICAL SKETCH

Curriculum Vitae

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Bruce S. Bochner, MD, is currently Professor of Medicine at the Johns Hopkins University School of Medicine in Baltimore, Maryland.  He joined the Division of Allergy and Clinical Immunology of the Department of Medicine in 1988, and in January 2003 became the Division Director.  He is a Fellow of the American Academy of Allergy Asthma and Immunology and the American College of Physicians, and a member of the American College of Allergy, Asthma & Immunology, the Association of American Physicians, American Association of Immunologists, the American Society for Clinical Investigation, and the Collegium Internationale Allergologicum.  He has been an Associate Editor for the Journal of Allergy and Clinical Immunology since 1993, is the Associate Editor for Clinical and Translational Medicine, and is an editor of the Middleton's Allergy: Principles and Practice textbook and the Allergy Section of UpToDate.  He served on the Board of Directors of the American Board of Allergy and Immunology and formerly served as  a member of the Immunological Sciences Study Section (now the Hypersensitivity, Autoimmune and Immune-Mediated Diseases Study Section) of the National Institutes of Allergy and Infectious Diseases.  He is the author of more than 180 peer-reviewed publications, reviews, and book chapters. He lectures extensively on a variety of topics, including both clinical and experimental aspects of allergic diseases.

Research Interests

Research interests include the mechanisms of allergic diseases and pathways regulating eosinophil, basophil and mast cell recruitment, activation and survival during allergic inflammatory responses.  Over the years, his work has focused on the role of cytokines (e.g., tumor necrosis factor, interleukins 4, 5 and 13), chemokines (e.g., eotaxins, MDC and TARC) and adhesion molecules (e.g., VLA-4, VCAM-1 and ICAM-1) in these events. Most recently, his lab studies the function, expression and genetics of Siglecs on human eosinophils, basophils and mast cells, especially Siglec-8 and Siglec-F.  He is also involved in a Program Project Grant studying the role of specific and total IgE in predicting allergic responses.

Current Research

Specific ongoing research projects include the following:

  1. The function and expression of Siglec-8 on human eosinophils, basophils and mast cells. Recent efforts are following up on the observation that crosslinking of Siglec-8 induces caspase-dependent apoptosis and inhibition of degranulation. Ongoing studies have identified a functional murine paralog of human Siglec-8, namely Siglec-F, and will allow additional studies of biological relevance. We are also determining the ability of Siglec-8/Siglec-F mAbs and ligand mimetics to limit allergic responses in eosinophils and mast cells in vitro and in vivo.
  2. Collaborative studies have led to the discovery of 6'-sulfated sialyl Lewis X as a candidate ligand for Siglec-8 and Siglec-F. Ongoing studies are characterizing natural Siglec-8/Siglec-F ligands and determining their tissue expression. We are exploring mechanisms by which Siglec-F and Siglec-8 engagement induces eosinophil apoptosis and inhibits mast cell mediator release.
  3. We are exploring the possibility that some human hypereosinophilic disorders, are due to genetic abnormalities in Siglec-8 function that occur, for example, as a result of altered or reduced tissue expression of 6'-sulfated sialyl Lewis X glycans, or mutations in the ligand binding or signaling domains of Siglec-8.
  4. In a separate series of collaborative experiments focused on human IgE biology and headed by my colleague Dr. Donald MacGlashan, we will explore whether a combination of the allergen-specific IgE and total IgE levels, especially the ratio of these two measurements, by influencing FceRI occupancy and density, determines the threshold and likelihood for cellular and clinical reactivity. This hypothesis is based in part on what our group and other laboratories have learned about how IgE, and an FDA-approved IgE-lowering antibody therapy, omalizumab, regulates basophil and mast cell responsiveness and surface density of FceRI. Given the half-life of mast cells in different tissue compartments and the slower onset of action of omalizumab on mast cells compared to that for basophils, we will test the hypothesis that food-induced anaphylaxis and late phase responses are basophil-dependent responses by performing skin, airway and oral allergen challenge within the first two weeks, and after months, of omalizumab administration. We also hypothesize that mechanisms responsible for trafficking of eosinophils to sites of airway late phase responses involve IgE-mediated triggering of recruited basophils, which then release mediators capable of activating epithelial chemokine production selective for eosinophils.

Lab

Bowling

Bochner Lab 2008-2009 (left to right:  Hui Mao, Bruce Bochner, Chang-Shin Park, Ho Jeong Na).
bochner lab
Bochner lab @ Baltimore Orioles ballgame - June 2010; top row L to R Dr. & Mrs. Takumi Kiwamoto, Dr. Yong Mean Park, Dr. Mi-Kyung Shin; bottom row Dr. Ho Jeong Na

Selected Publications

  1. Bochner, B.S.  Road signs guiding leukocytes along the inflammation superhighway. 
    J. Allergy Clin. Immunol.  106:817-828, 2000
  2. Kikly, K.K., Bochner, B.S., Freeman, S., Tan, K.B., Gallagher, K.T., D'Alessio, K., Holmes, S.D., Abrahamson, J., Hopson, C.B., Fischer, E.I., Erickson-Miller, C.L., Tachimoto, H., Schleimer, R.P., and White, J.R.  Identification of SAF-2, a novel glycoprotein expressed on eosinophils, mast cells and basophils. 
    J. Allergy Clin. Immunol. 105:1093-1100, 2000
  3. Bochner, B.S. and Schleimer, R.P.  Mast cells, basophils, and eosinophils: distinct but overlapping pathways for recruitment.
    Immunol. Reviews  179:5-15, 2001
  4. Burdick, M.M., Bochner, B.S., Collins, B.E., Schnaar, R.L., and Konstantopoulos, K.  Glycosphingolipids support E-selectin-specific strong cell tethering under flow. Biochem. Biophys. Res. Commun. 284:42–49, 2001
  5. Aizawa, H., Plitt, J., and Bochner, B.S.  Human eosinophils express two Siglec-8 splice variants. 
    J. Allergy Clin. Immunol. 109:176, 2002
  6. Tachimoto, H., Kikuchi, M., Hudson, S.A., Bickel, C.A., Hamilton, R.G., and Bochner, B.S.  Eotaxin-2 alters eosinophil integrin function via mitogen activated protein kinases.
    Am. J. Respir. Cell Molec. Biol. 26:645-649, 2002 (and editorial on p. 637)
  7. Nutku, T.E., Aizawa, H., Hudson, S.A., and Bochner, B.S. Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis.
    Blood 101:5014-5020, 2003
  8. Bochner, B.S.  Cellular adhesion in inflammation, in Middleton's Allergy Principles and Practice.  6th Edition. N.F. Adkinson, Jr., J.W. Yunginger, W.W. Busse, B.S. Bochner, S.T. Holgate, and F.E.R. Simons, editors, Mosby, St. Louis pp. 117-134, 2003
  9. Aizawa,H., Zimmermann,N., Carrigan, P.E., Lee, J.J., Rothenberg, M.E., and Bochner, B.S. Molecular cloning of mouse orthologs of Siglec-5 and Siglec-10: Comparison to human Siglec-8, mSiglec-E and mSiglec–F and analysis of expression in mouse tissues and eosinophils.
    Genomics 82:521-530, 2003
  10. Bochner, B.S., Hudson, S.A., Xiao, H.Q. and Liu, M.C.  Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late phase reactions.
    J. Allergy Clin. Immunol. 112:920-924, 2003
  11. Liu, Z., Kim, J., Sypek, J.P., Wang, I-M., Oppenheim, F.G., and Bochner, B.S.  Gene expression profiles in human nasal polyp tissues studied by DNA microarray.  J. Allergy Clin. Immunol. 114:783-790, 2004.
  12. Bochner, B.S.  Verdict in the case of therapies versus eosinophils:  the jury is still out.  J. Allergy Clin. Immunol. 113:3-9, 2004.
  13. Bochner, B.S., and Busse, W.W.  Advances in mechanisms of allergy.  J. Allergy Clin. Immunol. 113:868-875, 2004.
  14. Bochner, B.S., Alvarez, R.A., Mehta, P., Bovin, N.V., Blixt, O., White, J.R. and Schnaar, R.L.  Glycan array screening reveals a candidate ligand for Siglec-8.  J. Biol. Chem. 280:4307-4312, 2005.
  15. Nutku, E., Hudson, S.A., and Bochner, B.S. Mechanism of Siglec-8-induced human eosinophil apoptosis: role of caspases and mitochondrial injury.   Biochem. Biophys. Res. Commun. 336:918–924, 2005.
  16. Lim, L.H-K., Burdick, M.M., Hudson, S.A., Konstantopoulos, K., and Bochner, B.S.  Stimulation of human endothelium with interleukin 3 (IL-3) induces selective basophil accumulation in vitro.  J. Immunol. 176:5346-5353, 2006.
  17. Yokoi, H., Myers, A., Matsumoto, K., Crocker, P.R., Saito, H., and Bochner, B.S.  Alteration and acquisition of Siglecs during in vitro maturation of CD34+ progenitors into human mast cells. Allergy 61:769-776, 2006.
  18. Guo, J.P., Nutku, E., Yokoi, H., Schnaar, R.L., Zimmermann, N., and Bochner, B.S.  Siglec-8 and Siglec-F:  inhibitory receptors on eosinophils, basophils and mast cells.  Allergy Clin. Immunol. Inter. – J. World Allergy Org. 19:54-59, 2007.
  19. Nutku-Bilir, E., Hudson, S.A. and Bochner, B.S. Interleukin-5 priming of human eosinophils alters Siglec-8-mediated apoptosis pathways.  Am. J. Respir. Cell Molec. Biol.  2007.
  20. Conner, E., Bochner, B.S., Brummet, M., and Beck, L.A.  The effect of etanercept on the human cutaneous allergic response. J. Allergy Clin. Immunol. 121:258-260, 2008
  21. Yokoi, H., Choi, O.H., Hubbard, W., Lee, H.-S., Canning, B.J., Lee, H.H., Ryu, S.-D., Bickel, C.A., Hudson, S.A., MacGlashan, Jr., D.W. and Bochner, B.S. Inhibition of Fc?RI-dependent mediator release and calcium flux from human mast cells by Siglec-8 engagement.
    J. Allergy Clin. Immunol. 121:499-505, 2008
  22. Zimmermann, N., McBride, M.L., Yamada, Y., Hudson, S.A., Jones, C., Cromie, K., Crocker, P.R., Rothenberg, M.E. and Bochner, B.S.  Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils.
    Allergy 63:1156-1163, 2008.
  23. Matsumoto, K., Maeda, A., Bochner, B.S., Wakiguchi, H. and Saito, H.  Induction of apoptosis in human basophils by anti-Fas antibody treatment in vitro.
    Int. Arch. Allergy Immunol. 146 Suppl 1:40-46, 2008.
  24. Nimrichter, L., Burdick, M.M., Aoki, K., Laroy, W., Fierro, M.A., Hudson, S.A., Von Seggern, C.E., Cotter, R.J., Bochner, B.S., Tiemeyer, M., Konstantopoulos, K., and Schnaar, R.L.  E-selectin receptors on human leukocytes.
    Blood 112:3744-3752, 2008.
  25. Von Gunten, S. and Bochner, B.S.  Basic and clinical immunology of Siglecs.
    The Year in Immunology 2008.  Ann. N.Y. Acad. Sci. 1143: 61-82, 2008.
  26. Liu, Z., Lu, X., Zhang, X.H., Bochner, B.S., Long, X.B., Zhang, F., Wang, H., and Cui, Y.H.  Clara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosa. Allergy 64:149-57, 2009
  27. von Gunten, S., Smith, D.F., Cummings, R.D., Riedel, S., Miescher, S., Schaub, A., Hamilton, R.G. and Bochner, B.S. Intravenous immunoglobulin contains a broad repertoire of anti-carbohydrate antibodies that is not restricted to the IgG2 subclass.  J. Allergy Clin. Immunol. 123:1268-76, 2009.
  28. Hudson, S.A., Bovin, N., Schnaar, R.A., Crocker, P.R. and Bochner, B.S. Eosinophil selective binding and pro-apoptotic effect of a synthetic Siglec-8 ligand, polymeric 6’-sulfated sialyl Lewis X. J. Pharm. Exp. Therap. 330:608-612, 2009
  29. Gao, P.-S., Shimizu, K., Grant, A.V., Rafaels, N., Zhou, L.-F., Hudson, S.A., Konno, S., Zimmermann, N., Araujo, M.I., Ponte, E.V., Cruz, A.A., Nishimura, M., Su, S.-N., Hizawa, N., Beaty, T.H., Mathias, R.A., Rothenberg, M.E., Barnes, K.C. and Bochner, B.S.  Polymorphisms in the sialic acid-binding immunoglobulin-like lectin 8 (SIGLEC8) gene are associated with asthma in three independent ethnic populations.
        Eur. J. Human Genet.   20 January 2010 [Epub ahead of print]
  30. Guo, J.P., Brummet, M.E., Myers, A.C., Na, H.J., Rowland, E., Schnaar, R.L., Zheng, T., Zhu, Z. and Bochner, B.S.  Characterization of expression of glycan ligands for Siglec-F in normal mouse lung. Am. J. Respir. Cell Molec. Biol. (in press)

Last Updated: 7/31/2010

 
 
 
 
 

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