Program Director/Principal Investigator (Cannon , Judy, Lin): BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Judy L. Cannon Assistant Professor eRA COMMONS USER NAME (credential, e.g., agency login) jcanno EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) University of California at Berkeley San Francisco State University The University of Chicago The University of Chicago B.A. M.S. Ph.D. Postdoctoral 1995 1997 2003 2007 Biology Cell Biology Immunology Immunology Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical Sketch. A. Personal Statement The goal of the proposed project is to study how the signaling molecule PKCθ drives T cell migration downstream of CCR7. My training in immunology has focused on the understanding of how signaling networks function together to control T cell activation and migration. My predoctoral training in the laboratory of Dr. Janis Burkhardt used fluorescence microscopy and mutational analysis to identify the domains within the WiskottAldrich Syndrome Protein that regulated its localization to the immunological synapse. I then joined the laboratory of Dr. Anne Sperling to study the role of the molecule CD43 in regulating T cell function. In Dr. Sperling’s lab, I helped to identify a novel function for CD43 in regulating T cell migration. In work just accepted for publication in Molecular Biology of the Cell, I also showed the molecular requirements for CD43 regulation of T cell migration, including its interaction with the ezrin-radixin-moesin family of proteins. Since establishing my own laboratory as a newly appointed assistant professor at the University of New Mexico School of Medicine in March 2010, I have focused my work on identifying novel signaling regulators of T cell migration. I recently obtained evidence showing a novel role for PKCθ in controlling T cell migration, and will use the expertise gained in both my graduate and postdoctoral training to ascertain the precise mechanism by which PKCθ regulates T cell migration. My training combines all the tools I will need to accomplish the aims set out in my proposal. Under Dr. Burkhardt’s mentorship, I developed expertise in fluorescence microscopy to study the actin cytoskeleton and protein localization. In my postdoctoral training in Dr. Sperling’s lab, I used in vivo mouse models and flow cytometry to study T cell migration. I have extensive experience using structurefunction analyses to study molecular regulation of T cell activation and migration. In addition, I have now assembled a strong group of collaborators and consultants to help me accomplish my research aims in new areas of interest for my laboratory. The University of New Mexico Health Sciences Center is a NCI designated Cancer Center and I have developed working collaborations with two leukemia experts to assist me in developing an animal model to study T-ALL (Drs. Bridget Wilson and Stuart Winter). To study the role of CARMA1 and the NF-κB pathway, I have taken advantage of both research expertise and reagents from Dr. Marisa Alegre at the University of Chicago who specializes in the study of CARMA1 and NF-κB in T cell function. Dr. Jordan Jacobelli and Rachel Friedman, recently appointed new Assistant Professors at the National Jewish Health Center and University of Colorado have agreed to provide technical advice and assistance for multiphoton microscopy and intravital imaging. My own training and my team of consultants and collaborators put me in a strong position to use the cutting edge fluorescence expertise and technology available to me at the University of New Mexico to accomplish the aims set out in this proposal. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Cannon , Judy, Lin): B. Positions and Honors Positions and Employment 1995 Lawrence Berkeley Laboratories, Human Genome Project, Technician, Berkeley, CA. 1995-1997 Master’s Degree candidate, Cell Biology, Department of Biology, SFSU, SF, CA. 1997-2003 Predoctoral Fellow, Committee on Immunology, Univ. of Chicago, Chicago, IL. 2003-2008 Postdoctoral Fellow, Dept. of Med Pulmonary and Critical Care Med, Univ. of Chicago. 2008-2010 Research Associate (Assistant Professor), Department of Medicine, Section of Pulmonary & Critical Care, The University of Chicago, Chicago, IL. 2010-present Assistant Professor, Depts of Molecular Genetics and Microbiology and Pathology, Univ of New Mexico Health Sciences Center, Albuquerque, NM. Other Experience and Professional Memberships 2007 – present American Association of Immunologists Honors 1991-1995 1995-1997 1997-2000 2003-2005 2005-2008 2008 Chancellor’s Scholarship, University of California at Berkeley, Berkeley, CA. GAANN Fellowship, San Francisco State University, San Francisco, CA. Searle Fellowship, University of Chicago, Chicago, IL. NIH Post-doctoral Fellowship, University of Chicago, Chicago, IL. Cancer Research Institute Post-doctoral Fellowship. Huggins Lectureship, University of Chicago, Chicago, IL. C. Selected Peer-reviewed Publications Most relevant to the current application 1. Cannon, J.L.#, Mody, P.D., Blaine, K.M., Nelson, A.D., Sayles, L., Moore, T.V., Clay, B.S., Bandukwala, H.S., Dulin, N.O., Shilling, R.A., Sperling, A.I. CD43 interaction with ERM proteins regulates T cell trafficking and CD43 phosphorylation. Molecular Biology of the Cell, in press. #corresponding author. 2. Mody, P.D.*, Cannon, J.L.*, Bandukwala, H.S., Blaine, K.M., Schilling, A.B., Swier K., Sperling, A.I. 2007. Signaling through CD43 is required for CD4 T cell trafficking. Blood, Oct 15;110(8):2974-82. *co-first authorship. PMID: 17638845. 3. Cannon, J.L., Burkhardt, J.K. Differential roles for WASP in actin regulation and IL2 production. 2004. Journal of Immunology 173(3):1658-62. 4. Zeng, R., Cannon, J.L., Abraham, R.T., Way, M., Billadeau, D.D., Bubeck-Wardenberg, J., Burkhardt, J.K. 2003. SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. Journal of Immunology 171(3):1360-8. PMID: 12874226. 5. Cannon, J.L., C. Case, G. Bosco, A. Seth, M. McGavin, K.A. Siminovitch, M.K. Rosen, and J.K. Burkhardt. 2001. WASP recruitment to the T cell-APC contact site occurs independently of Cdc42 Activation. Immunity 15:249-259. PMID: 11520460. Additional recent publications 6. Sedwick, C.E., M.M. Morgan, L. Jusino, J.L. Cannon, J. Miller and J.K. Burkhardt. 1999. TCR, LFA-1 and CD28 play unique and complementary roles in T cell cytoskeletal reorganization. Journal of Immunology 162:1367-1375. PMID: 9973391. 7. Allenspach, E.J., P. Cullinan, J. Tong, Q. Tang, A.G. Tesciuba, J.L. Cannon, S.M. Takahashi, R. Morgan, J.K. Burkhardt, and A.I. Sperling. 2001. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity, 15:739-750. PMID: 11728336 PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Cannon , Judy, Lin): 8. Bandukwala, H.S., B.S. Clay, J. Tong, P.D. Mody, J.L. Cannon, R.A. Shilling, J.S. Verbeek, J.V. Weinstock, J. Solway, and A.I. Sperling. 2006. Signaling through FcγRIII is required for optimal Th2 responses and Th2mediated airway inflammation. Journal of Experimental Medicine 204(8):1875-89. PMID: 17664287 9. Cannon, J.L. *#, Collins A. *, Balachandran D., Henriksen, K.J., Clay, B.S., Mody, P.D., Smith, C.E., Tong J., Miller S.D., Sperling A.I. 2008. CD43 regulates Th2 differentiation and inflammation. Journal of Immunology, 180: 7385-7393. *co-first authorship, #corresponding author. PMID: 18490738 10. Shilling, R.A., Clay, B.S., Moore, T.V., Berry, E., Tesciuba, A.G., Bandukwala, H.S., Tong, J., Weinstock, J.V., Flavell, R.A., Horan, T., Yoshinaga S.K., Welcher, A.A., Cannon, J.L., Sperling, A.I. 2009. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. Cellular Immunology, 2009;259(2):177-84. PMID: 19646680 11. Clay BS, Shilling RA, Bandukwala HS, Moore TV, Cannon JL, Welcher AA, Weinstock JV, Sperling AI. 2009. Inducible costimulator expression regulates the magnitude of Th2-mediated airway inflammation by regulating the number of Th2 cells. PLoS One. Nov 4;4(11):e7525. PMID: 19888475 12. Shaffer MH, Huang Y, Corbo E, Wu GF, Velez M, Choi JK, Saotome I, Cannon JL, McClatchey AI, Sperling AI, Maltzman JS, Oliver PM, Bhandoola A, Laufer TM, Burkhardt JK. 2010. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PLoS One. 2010 Aug 27;5(8). pii: e12404. PMID: 20806059 13. Driessens, G., Zheng, Y., Locke, F., Cannon, J.L., Gounari, F., Gajewski, T.F. β-catenin inhibits T cell activation by selective interference with LAT-PLC-γ1 phosphorylation. Journal of Immunology, in press. PMID: 21149602 14. Moore TV, Clay BS, Ferreira CM, Williams JW, Rogozinska M, Cannon JL, Shilling RA, Marzo AL, Sperling AI. Protective effector memory CD4 T cells depend on ICOS for survival. PLoS One. 2011 Feb 18;6(2):e16529. PMID: 2136474 15. Moore TV, Clay BS, Cannon JL, Histed A, Shilling RA, Sperling AI. ICOS Controls T Cell Migration to the Lungs via Down-Regulation of CCR7 and CD62L. Am J Respir Cell Mol Biol. 2011. Vol. 45, pp. 843-850, 2011. PMID: 21421907 D. Research Support Ongoing Research Support Scientist Development Grant Cannon (PI) 7/1/09-6/30/13 American Heart Association PKCθ phosphorylation of CD43 via ERM proteins regulates T cell trafficking Study the molecular regulation of T cell trafficking by PKCθ, ERM proteins, and CD43 and define the mechanism of molecular interaction between PKCθ, ERM proteins, and CD43. Role: PI R01 AI097202-01A1 Cannon (PI) 5/1/12-4/30/17 The role of PKCtheta in T cell and T-ALL migration The goal of this application is to elucidate the mechanisms involved in controlling T cell migration and migration of T-ALL leukemia cells. Role: PI 1R21HL106462 NIH/NHLBI PHS 398/2590 (Rev. 06/09) Corey, Seth (PI) Page 10/01/11-06/30/13 Biographical Sketch Format Page Program Director/Principal Investigator (Cannon , Judy, Lin): The F-BAR protein CIP4 in WASP dependent thrombocytopenia The goal of this project is to model T cells searching for antigen in lymph nodes. Role: Subaward Completed Research Support Illinois Division Research Grant Cannon (PI) 12/01/08-11/30/09 American Cancer Society-IL. Division PKCθ phosphorylation of CD43 via ERM proteins regulates T cell trafficking The goal of this project is to delineate the signaling pathways that lead to CD43 phosphorylation and normal T cell trafficking to lymph nodes, specifically, the roles of ERM proteins and PKCθ. Role: PI PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page