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Analysis of mDia formins in hematopoietic stem cell engraftment and migration

mDia 福明在造血干细胞植入和迁移中的分析

基本信息

批准号：
8669055
负责人：
Peng Ji
金额：
$ 23.91万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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：
2010-06-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8669055
关键词：
Acetylation Actins Affect Aplastic Anemia Area Arts Backcrossings Binding Proteins Biochemical Biological Assay Biological Sciences Blood Blood Cells Bone Marrow Bone Marrow Transplantation Burn injury C57BL/6 Mouse Cell Adhesion Cell Lineage Cells Cellular biology Clinical Co-Immunoprecipitations Collaborations Complex Cooley&apos s anemia Cytoskeletal Proteins Cytoskeleton Data Deacetylase Deacetylation Disease Doctor of Philosophy Engraftment Environment Erythroblasts F-Actin Family Fanconi&apos s Anemia Fetal Liver Fibronectins Generations Goals Guanosine Triphosphate Phosphohydrolases HDAC6 gene Hematopoietic Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Homing Immunologic Deficiency Syndromes In Vitro Institutes Kinetics Knockout Mice Laboratories Light Mammals Mass Spectrum Analysis Mediating Medicine Mentors Mentorship Microfilaments Microscopy Migration Assay Modification Molecular Molecular Biology Multiple Myeloma Mus Myosin Type II Patients Phosphorylation Play Post-Translational Protein Processing Process Protein Family Proteins Publishing Regulation Research Research Personnel Role Scientist Sickle Cell Anemia Signal Pathway Singapore Stem Cell Research Stem cells T-Lymphocyte Techniques Time TimeLine Training Transplantation Umbilical Cord Blood Work beta Thalassemia career cell motility cell type college embryonic stem cell experience hematopoietic tissue in vivo interest leukemia/lymphoma loss of function macrophage migration mouse model novel polymerization research study skills stem cell population vector

项目摘要

I am a MD/PhD postdoctoral scientist with extensive training in molecular and cell biology from Albert Einstein College of Medicine and Whitehead Institute. My research focuses on the roles of the mDia formin proteins on hematopoietic cells. The mDia formin proteins have well-established roles on the migration of many different cell types. However, their effects on the migration of hematopoietic cells, especially hematopoietic stem cells (HSCs), are poorly understood. With the ideal research environment of Whitehead Institute and excellent mentorship of Dr. Harvey Lodish, I plan to expand my existing scientific and intellectual skills by developing expertise in areas of hematopoeitic stem cells and cell migration, which is vital to my long term career goal of becoming a successful, independent investigator. The goal of my proposed study is to characterize the functional roles of mDia formins, specifically mDia1 and mDia2, on hematopoietic stem cell (HSC) engraftment and migration. HSC engraftment and migration are critical for successful bone marrow transplantation, which has become a routine clinical strategy for treating patients with many blood related diseases such as aplastic anemia, fanconi anemia, sickle cell anemia, beta thalassemia major, leukemia, lymphomas, multiple myeloma, and many immune deficiency disorders. The intracellular signaling pathways regulating HSC engraftment and migration often directly or indirectly target on the actin cytoskeleton network through proteins that regulate polymerization of the actin proteins. The mDia formin proteins are a major actin-nucleating family and their functions in HSCs are poorly understood. To elucidate the roles of mDia formins, specifically mDia1 and mDia2, on HSC migration, genetically modified mouse models and molecular cell biology techniques will be used. Specifically, mouse models deficient of mDia1 or mDia2 will be generated. With these mice, bone marrow and fetal liver Lin-Sca1+Kit+ (LSK) cells, an enriched HSC population, will be purified to perform in vitro migration assays, short-term homing, and long- term engraftment analysis. In collaboration with Drs. Tzutzuy Ramirez Hernandez and Maki Murata-Hori of the Temasek Life Sciences Laboratory in Singapore, the kinetic interactions of mDia1 and mDia2 with actin cytoskeletal proteins and how these interactions regulate hematopoietic stem cell migration will be investigated using confocal fluorescent microscopy and mass spectrometry analysis. In addition, post-translational modifications of mDia1 and mDia2, especially acetylation and phosphorylation, and how these modifications affect their functions in HSC migration will also be characterized.

我是一名医学博士/博士后科学家，在阿尔伯特大学接受过分子和细胞生物学方面的广泛培训