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.

Selected Publications
Taylor, P.R., Roy, S., Leal, Jr. S.M., Sun, Y., Howell, S.J., Cobb, B.A., Li, X., Pearlman, E. (2013) “Autocrine IL-17A/IL-17RC neutrophil activation in fungal infections is regulated by IL-6, IL-23, RORγt and Dectin-2”, Nature Immunology, in press.

Ryan, S.O., Leal Jr., S.M., Abbott, D.W., Pearlman, E., Cobb, B.A. (2013) “Mgat2 ablation in the myeloid lineage leads to defective glycoantigen T cell responses”, Glycobiology, in press.

Jun, J.C., Kertesy, S., Jones, M.B., Marinis, J.M., Cobb, B.A., Tigno-Aranjuez, J.T., Abbott, D.W. (2013) “Innate Immune-Directed NF-kB Signaling Requires Site-Specific NEMO Ubiquitination”, Cell Reports 4(2), pp. 352-361.  [PMCID: in process]

Bloem, K., Garvia-Vallejo,J.J., Vuist, I.M., Cobb, B.A., van Vliet, S.J., van Kooyk, Y. (2013) “Interaction of the Capsular Polysaccharide A from Bacteroides fragilis with DC-SIGN on Human Dendritic Cells in Necessary for its Processing and Presentation to T cells”, Front. Immunol. 4, pp. 103 [PMCID: PMC3644800]

Ryan, S.O., Johnson, J.L., Cobb, B.A. (2013) “Neutrophils confer T cell resistance to myeloid-derived suppressor cell-mediated suppression to promote chronic inflammation”, J. Immunol. 190(10), pp. 5037-5047.  [PMCID: PMC3647005]

Xiao, X., Yuan, J., Haik, S., Cali, I., Zhan, Y., Li, B., Moudjou, M., Laplanche, J-L., Laude, H., Langeveld, J., Gambetti, P., Kitamoto, T., Kong, Q., Cobb, B.A., Brandel, J-P., Petersen, R.B., Zou, W-Q. (2013) “Glycoform-selective prion formation in sporadic and familial forms of prion disease”, PLOS One 8(3), e58786.  [PMCID: PMC3602448]

Johnson, J.L., Jones, M.B., Ryan, S.O., Cobb, B.A. (2013) “The Regulatory Power of Glycans and their Binding Partners in Immunity”, Trends in Immunology 34(6), pp. 290-298.  [PMCID: PMC3674136]

Ryan, S.O., Cobb, B.A.  (2012) “Host glycans and antigen presentation”, Microbes and Infection 14, pp. 894-903.  [PMCID: PMC3432721]

Leal Jr., S.M., Vareechon, C., Cowden, S., Cobb, B.A., Latge, J-P., Momany, M., Pearlman, E.  (2012) “Fungal Antioxidant Pathways Promote Survival Against Neutrophils During Infection”, J. Clin. Invest. 122(7), pp. 2482-2498.  [PMCID: PMC3534057]

Taylor, C.E., Cobb, B.A., Rittenhouse-Olson, K., Paulson, J., Schreiber, J.R.  (2012) “Carbohydrate Moieties as Vaccine Candidates: Targeting the sweet spot in the immune response”, Vaccine 30(30), pp. 4409-4413.  [PMID: 22575168]

Kreisman, L.S.C. and Cobb, B.A.  (2012) “Host Glycosylation and Infection: A Glyco-Evasion Hypothesis”, Glycobiology 22(8), pp. 1019-1030.  [PMCID: PMC3382345]

Marinis, J.M., Hutti, J.E., Homer, C.R., Cobb, B.A., Cantley, L.C., McDonald, C., Abbott, D.W.  (2012) “IκB Kinase α Phosphorylation of TRAF4 Down-Regulates Innate Immune Signaling”, Mol. Cell Bio. 32(13), pp. 2479-2489.  [PMCID: PMC3434482]

Ryan, S.O. and Cobb, B.A.  (2012) “Roles for Major Histocompatibility Complex Glycosylation in Immune Function", Sem. Immunopath. (SIM) special volume on Glycosylation and Immunity 34(3), pp. 425-441.  [PMID: 22461020]

Rabinovich, G.A., van Kooyk, Y., Cobb, B.A.  (2012) “Glycobiology of Immune Responses”, Ann. NY Acad. Sci. 1253(1), pp. 1-15.  [PMID: 22524422]

Lewis, C.J. and Cobb, B.A.  (2011) “Adaptive Immune Defects Against Glycoantigens in Chronic Granulomatous Disease via Dysregulated Nitric Oxide Production", Euro. J. Immunol. 41(9), pp. 2562-2572.  [PMCID: PMC3215277]

Young, N.M., Kreisman, L.S.C., Stupak, J., Maclean, L.L., Cobb, B.A., Richards, J.C.  (2011) "Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii", Glycobiology 21(10), pp. 1266-1276.  [PMCID: PMC3167475]

Ryan, S.O., Bonomo, J.A., Zhao, F., Cobb, B.A.  (2011) "MHCII Glycosylation Modulates Bacteroides fragilis Carbohydrate Antigen Presentation", J. Exp. Med. 208(5), pp. 1041-1053. [PMCID: PMC3092352]

Kreisman, L.S.C. and Cobb, B.A. (2011) "Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization", J. Biol. Chem. 286(11), pp. 8810-8818. [PMCID: PMC3059040]

Lewis, C.J., Cobb, B.A. (2010) "Carbohydrate Oxidation Acidifies Endosomes, Regulating Antigen Processing and TLR9 Signaling", J. Immunol. 184, pp. 3789-3800.  [PMCID: PMC2902972]

Brokaw, A., Cobb, B.A. (2009) “A Simple Test Tube-Based ELISA Experiment for the High School Classroom”, Biochem. Mol. Bio. Ed. 37(4), pp. 243-248.  [PMCID: PMC2915469]

Velez, C.D., Lewis, C.J., Kasper, D.L., Cobb, B.A. (2009) “Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHCII-dependent pathway for antigen presentation”, Immunol. 127(1), pp. 73-82.  [PMCID: PMC2678183]

Clark, N.M., Marinis, J.M., Cobb, B.A., Abbott, D.W. (2008) “MEKK4 Sequesters RIP2 to Dictate Signal Specificity Downstream of the Crohn’s Disease Susceptibility Protein, NOD2”, Curr. Biol. 18(18), pp. 1402-1408. [PMCID: PMC2581469]

Cobb, B.A., Kasper, D.L. (2008) “Characteristics of carbohydrate antigen binding to the presentation protein HLA-DR”, Glycobiology 18(9), pp. 707-718. [PMCID: PMC2733769]

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.  [PMCID: PMC2902978]

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”, J. Exp. Med. 203(13), pp. 2853-2863.  [PMCID: PMC2118167]

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.  [PMCID: PMC2917993]

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.