Brian A. Cobb, Ph.D. Associate Professor Mailing Address: 2103 Cornell Rd. WRB 6532 Cleveland, OH 44106-7288 phone: (216) 368-1263 fax: (216) 368-0494 email: Brian.Cobb@Case.edu

Laboratory

Biography
Dr. Brian Cobb graduated with a B.S. in Biochemistry from the University of Oklahoma in 1995. The next five years were spent at Washington University, St. Louis, where he received his Ph.D. in Biochemistry studying the macromolecular interactions of the lens protein alpha crystallin with the plasma membrane. His three years as a postdoctoral fellow was spent as a dual appointment in the Department of Microbiology and Molecular Genetics and the Department of Medicine at Harvard Medical School (2001-04) working with Dennis Kasper on the innate and adaptive immune responses to commensal bacteria-derived capsular polysaccharides. He continued at Harvard for another year as an Instructor before coming to Case School of Medicine in 2005 where he holds an Associate Professorship in the Department of Pathology.

Research
The Cobb lab focuses on a new immunologic paradigm: the antigen processing and presentation of carbohydrate antigens. The adaptive response to these "glycoantigens" is a T cell-dependent pathway that we now believe to be critical for the maintenance of immune homeostasis throughout the body, including potent anti-inflammatory activity that can prevent the onset of inflammatory bowel disease and even experimental autoimmune encephalomyelitis (EAE) - a model for multiple sclerosis. Our work is highly multifaceted and affords opportunities for cellular immunology (antigen presenting cell and T cell biology), animal models, molecular biology, and biochemistry (structure/function and macromolecular interactions). We believe this work to be very exciting because of the potential for translational application in the form of new vaccines against glycoantigen-carrying pathogenic organisms as well as the application of probiotic commensal bacteria to the prevention of inflammatory disease. More details about our work can be found on our lab website.

Publications
Ramachandra, L., Qu, Y., Wang Y., Lewis, C.J., Cobb, B.A., Takatsu, K., Boom, W.H., Dubyak, G.R., Harding, C.V. (2010) "Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing MHC-II molecules capable of antigen presentation", Infection and Immunity 78(12), pp. 5116-5125. [Pubmed]

Lewis, C.J., Cobb, B.A. (2010) "Carbohydrate Oxidation Acidifies Endosomes, Regulating Antigen Processing and TLR9 Signaling", Journal of Immunology 184, pp. 3789-3800. [Pubmed]

Brokaw, A., Cobb, B.A. (2009) "A Simple Test Tube-Based ELISA Experiment for the High School Classroom", Biochemistry and Molecular Biology Education 37(4), pp. 243-248. [Pubmed]

Cobb, B.A. (2009) "Immunology and the biomedical student pipeline", European Journal of Immunology 39(5), pp. 1183-1186. [Pubmed]

Velez, C.D., Lewis, C.J., Kasper, D.L., Cobb, B.A. (2008) "Type 1 Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHCII-dependent pathway for antigen presentation", Immunology 127(1), pp. 73-82. [Pubmed]

Clark, N.M., Marinis, J.M., Cobb, B.A., Abbott, D.W. (2008) "MEKK4 sequesters RIP2 to dictate NOD2 signal specificity", Current Biology 18(18), pp. 1402-1408. [Pubmed]

Cobb, B.A., Kasper, D.L. (2008) "Characteristics of carbohydrate antigen binding to the presentation protein HLA-DR", Glycobiology 18(9), pp. 707-718. [Pubmed]

Kreisman, L.S.C., Friedman, J.H., Neaga, A., Cobb, B.A. (2007) “Structure-Function Relationships with a T cell Activating Polysaccharide Antigen using Circular Dichroism”, Glycobiology 17(1), pp. 46-55. [Pubmed]

Wang, Q., McLoughlin, R.M., Cobb, B.A., Charrel-Dennis, M., Zaleski, K.J., Golenbock, D., Tzianabos, A.O., Kasper, D.L. (2006) "A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2", Journal of Experimental Medicine 203(13), pp. 2853-2863. [Pubmed]

Cobb, B.A., Kasper, D.L. (2005) "Zwitterionic Capsular Polysaccharides: The New MHCII-Dependent Antigens", Cellular Microbiology 7(10), pp. 1398-1403. [Pubmed]

Cobb, B.A., Kasper, D.L. (2005) "Coming of Age: Carbohydrates and Immunity", European Journal of Immunology 35(2), pp. 352-356.  [Pubmed]

Cobb, B.A., Wang, Q., Tzianabos, A.O., Kasper, D.L. (2004) "Polysaccharide Processing and Presentation by the MHCII Pathway", Cell 117(5), pp. 677-87.  [Pubmed]

Cobb, B.A., Petrash, J.M. (2002) "Factors Influencing alpha-Crystallin Association with  Phospholipid Vesicles", Molecular Vision 8, pp. 85-93.  [Pubmed]

Cobb, B.A., Petrash, J.M. (2001) "Alpha-Crystallin Chaperone-Like Activity and Membrane Binding in Age-Related Cataracts", Biochemistry 41, pp. 483-90.  [Pubmed]

Cobb, B.A., Petrash, J.M. (2000) "Structural and Functional Changes in the alphaA-crystallin R116C Mutant in Hereditary Cataracts", Biochemistry 39, pp. 15791-8.  [Pubmed]

Cobb, B.A., Petrash, J.M. (2000) "Characterization of alpha-Crystallin-Plasma Membrane Binding", Journal of Biological Chemistry 275(9), pp. 6664-72.  [Pubmed]

Stock, M.F., Guerrero, J., Cobb, B., Eggers, C.T., Huang, T-G, Li, X., Hackney, D.D. (1999) "Formation of the Compact Confomer of Kinesin Requires a COOH-terminal Heavy Chain Domain and Inhibits Microtubule-Stimulated ATPase Activity", Journal of Biological Chemistry 274(21), pp. 14617-23.  [Pubmed]

Third-Party News and Views

Watts, C. (2004) "Class II MHC: Sweetening the Peptide-Only Diet?", Cell 117(5), pp. 558-9.  [Pubmed]

Honey, K. (2004) "Presenting a Newly Charged Antigen", Nature Reviews Immunology 4, pg. 489.

Hurtley, S.M. (2004) "Immunology: Sweet Presentation", Science 304, pg. 1719.

Dempsey, L.A. (2004) "Processed Sugar", Nature Immunology 5(7), pg. 693.