Applicant: The applicant, Dr. Harris, has demonstrated long standing commitment and excellence in every phase of her training. Dr. Harris has participated in basic science investigation of the role of beta1 integrins in pulmonary T cell mediated inflammation for the past thirty months while in the laboratories of Drs. Yoji Shimizu and Stephen Hunt. During her tenure at the University of Michigan, she characterized a beta1 integrin negative mutant cell line, invented a transient-transfection adhesion assay for detecting changes in adhesive activity, published in peer reviewed journals and presented her findings at major national and international meetings. Dr. Harris displays a high level of competence, enthusiasm and integrity in her patient care, teaching and research activities. Environment: The Division of Respiratory, Critical Care and Occupational Pulmonary Medicine has a long and successful track record of training clinician-scientists, and the University of Utah's Medical Center is a premier institution for medical research. Dr. Harris was recently appointed as an Instructor of Internal Medicine at The University of Utah Medical Center and has joined the laboratory of Dr. Guy Zimmerman in the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI). Along with Dr. Zimmerman, Drs. Shimizu, Hunt, Lorant and Hoidal will serve as advisors and meet regularly with Dr. Harris to discuss results, experimental design and manuscripts. Research: T cell mediated immune response plays an important role in pulmonary illnesses including asthma, ARDS and transplant rejection. The beta1 integrin family of cell surface adhesion proteins play a critical role in T cell trafficking. Therapeutic strategies aimed at down regulation of the integrin-mediated adhesive component of lymphocyte migration and recruitment to the lungs would have significant clinical impact on many pulmonary illnesses. Our hypothesis is that the specific regions of the beta1 cytoplasmic domain are crucial for activation-induced regulation of integrin activity.
Aim #1 : Determine which regions of the 131 cytoplasmic domain are crucial for activation-induced regulation of integrin activity.
Aim #2 : Evaluation of the role of the alternative beta1 integrin cytoplasmic domains in activation induced regulation of integrin activity.
Aim #3 : Identification of novel proteins that interact with the beta1A and beta1C cytoplasmic domains in T cells during activation induced upregulation of integrin activity.
| Bunting, Michaeline; Harris, Estelle S; McIntyre, Thomas M et al. (2002) Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands. Curr Opin Hematol 9:30-5 |
| Galt, S W; Lindemann, S; Medd, D et al. (2001) Differential regulation of matrix metalloproteinase-9 by monocytes adherent to collagen and platelets. Circ Res 89:509-16 |
| Harris, E S; Shigeoka, A O; Li, W et al. (2001) A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by beta1 and beta2 integrins. Blood 97:767-76 |
| Harris, E S; McIntyre, T M; Prescott, S M et al. (2000) The leukocyte integrins. J Biol Chem 275:23409-12 |
