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In vivo role of BTK-mediated inhibition of Wnt/b-catenin signaling during hematop

BTK 介导的 Wnt/b-catenin 信号抑制在 hematop 过程中的体内作用

基本信息

批准号：
8532963
负责人：
Richard Goff James
金额：
$ 23.29万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-14 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532963
关键词：
Adult Amino Acids Animal Disease Models Area Attention Award B-Lymphocytes Basic Science Biological Models Blood Cells Bone Marrow Bone Marrow Transplantation Cancer cell line Cell Culture Techniques Cell Line Cells Chemicals Clinical Colorectal Cancer Data Development Diagnosis Embryo Engraftment Event Flow Cytometry Galactosidase Gene Targeting Genetic Suppression Hematopoiesis Hematopoietic System Hematopoietic stem cells Home environment Human Investigation Knowledge Large Intestine Carcinoma Learning Mass Spectrum Analysis Mediating Methods Mission Modeling Molecular Monitor Mus Mutation National Heart, Lung, and Blood Institute Pathway interactions Patients Peptides Phosphorylation Positioning Attribute Proteomics Regulation Reporter Research Personnel Role Sampling Signal Pathway Signal Transduction Small Interfering RNA Sorting - Cell Movement Spleen Stable Isotope Labeling Stem cells Symptoms TEC Protein Tyrosine Kinase Techniques Testing Training Umbilical Cord Blood Umbilical cord structure Work X-Linked Agammaglobulinemia Zebrafish abstracting base cancer therapy chemical genetics gain of function improved in vitro Model in vivo interest kinase inhibitor loss of function post-doctoral training reconstitution research study small molecule tissue culture

项目摘要

Project Abstract Currently I am using chemical genetics, siRNA screens and mass spectrometry- based proteomics to probe the Wnt/ -catenin signaling pathway. Using these techniques we identified Tec kinases as negative regulators of Wnt/ -catenin signaling. Because mutations in the Tec kinase BTK are responsible for X-linked agammaglobulinemia, we sought to corroborate our original findings in B cells. We found that Tec kinases also negatively regulate Wnt/ -catenin signaling in B cells in culture. This work has led me to the hypothesis that the interplay of Tec kinases and Wnt signaling will have a significant role in hematopoiesis in vivo. I am applying for the Pathway to Independence Award in order to extend my postdoctoral training so that I can learn about animal models of disease and hematopoiesis and gain practical knowledge of how to dissect mice and collect bone marrow, how to perform murine bone marrow transplantation experiments and how to analyze these experiments by flow cytometry. As outlined in the proposal, I will use all of these methods in order to test my hypothesis. As an independent investigator I plan to exploit my unique position at the intersection of proteomics and hematopoiesis to explore the molecular mechanisms of signal transduction in cellular differentiation. Not only would this direction allow me to fully utilize my training to date, it would allow me to enter a field that has important clinical implications, such as cord blood engraftment, bone marrow transplant and cancer treatments.

项目摘要