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BCL10-MALT1 protein-protein interaction in lymphocyte function and dysfunction

BCL10-MALT1 蛋白-蛋白相互作用在淋巴细胞功能和功能障碍中的作用

基本信息

批准号：
10722751
负责人：
Lisa M Maurer
金额：
$ 17.32万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-12 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722751
关键词：
Achievement Affect Animal Model Antigen Receptors Antigens Authorship Autoimmune Award B-Lymphocytes BCL10 gene Biochemistry Bioinformatics Biometry Cells Colitis Complex Development Plans Disease Disease model Educational Status Educational workshop Environment Event Experimental Designs Functional disorder Goals Grant Growth Immune Immune System Diseases Immunoglobulin Domain Immunology In Vitro Inflammation Inflammatory K-Series Research Career Programs Knowledge Laboratories Lymphocyte Lymphocyte Activation Lymphocyte Biology Lymphocyte Function Lymphocyte Subset Lymphoma Malignant - descriptor Malignant Neoplasms Manuscripts Mentors Mentorship Molecular Mucosa- associated lymphoid tissue lymphoma translocation protein-1 Mus Organ Pathogenesis Pathology Patient-Focused Outcomes Peptide Hydrolases Phenotype Physicians Play Positioning Attribute Preparation Production Productivity Proliferating Protease Inhibitor Protein Biochemistry Proteomics Psoriasis Records Regulatory T-Lymphocyte Research Role Scientist Seminal Signal Transduction Signaling Protein T-Lymphocyte T-Lymphocyte Subsets Technical Expertise Techniques Therapeutic Training Transcriptional Activation Universities Work Xenograft procedure biomedical scientist career career development cytokine immune system function improved improved outcome in vivo in vivo Model inhibitor insight lymphocyte proliferation meetings mouse model murine colitis pharmacologic programs protein complex protein protein interaction recruit research and development response responsible research conduct scaffold skills small molecule systemic inflammatory response transcription factor transcriptomics

项目摘要

The goal of this career development award is for the applicant to gain knowledge and technical expertise in lymphocyte biology in order to advance our understanding of how the interaction between BCL10 and MALT1, two critically important lymphocyte signaling proteins, influences lymphocyte function and dysfunction. Knowledge gained during this career development award will provide new insights into the mechanism of interaction between BCL10 and MALT1 as well as the molecular pathogenesis of immune disorders associated with MALT1 dysregulation, including psoriasis and colitis. Experiments are designed with the ultimate goal of determining the therapeutic potential of targeting the BCL10-MALT1 protein-protein interaction in these inflammatory disorders. Specifically, the proposed studies will investigate how manipulation of the BCL10- MALT1 interaction affects MALT1 activity, proinflammatory lymphocyte signaling, and progression of psoriasis and colitis. The proposed experimental aims utilize sophisticated protein biochemistry techniques, in-depth in vitro analyses of lymphocyte function, robust in vivo models of inflammatory disease, and detailed bioinformatic analyses. The applicant has selected a mentor and co-mentor who have strong track records of both research mentorship and scientific achievement and who are therefore well positioned to provide expert guidance. Additionally, the applicant has constructed a career mentoring committee with expertise in developing small molecule protein-protein interaction inhibitors, in lymphocyte biology, and in the analysis of animal models of inflammatory disease. The applicant has also identified key collaborators with needed expertise in immune dysfunction in psoriasis and in biostatistics. The University of Pittsburgh provides a fantastic environment in which to launch an independent career as a productive biomedical scientist. The primary mentor and co-mentor are committed to guiding the applicant towards a highly successful career as a physician scientist via a formal program of scientific and professional milestone assessments. Key milestones emphasize the mastery of specific scientific techniques, the development of research mentoring skills, the transition to senior/corresponding authorship of scientific manuscripts and the preparation of the applicant to initiate her own independent laboratory program. The applicant’s career development plan was carefully crafted to take full advantage of the outstanding environment at University of Pittsburgh including graduate level course work in immunology and biochemistry, workshops and formal coursework in bioinformatics, didactics in murine models of disease, face- to-face career development workshops offered through the Office of Academic Career Development, and workshops in Responsible Conduct of Research. The applicant has identified opportunities to present her work locally as well as at national meetings. With full support of her mentor and co-mentor, the applicant is excited to pursue this training in order to launch her career as an independent scientist studying the influence of key protein- protein interactions in lymphocyte function and dysfunction at the University of Pittsburgh.

这个职业发展奖项的目标是让申请人获得以下方面的知识和技术专长