Genomes and Genes
Analysis of mDia formins in hematopoietic stem cell engraftment and migration
Principal Investigator: Peng Ji
Abstract: 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.
Funding Period: 2010-06-01 - 2015-05-31
more information: NIH RePORT
- Ankyrin and band 3 differentially affect expression of membrane glycoproteins but are not required for erythroblast enucleationPeng Ji
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Biochem Biophys Res Commun 417:1188-92. 2012..However, neither band 3 nor ankyrin are required for enucleation. These results demonstrate that mammalian erythroblast enucleation does not depend on the membrane integrity generated by the ankyrin-band 3 complex...
- Mammalian erythroblast enucleation requires PI3K-dependent cell polarizationJunxia Wang
Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604 Singapore
J Cell Sci 125:340-9. 2012..We propose that enucleation is regulated by microtubules and PI3K signaling in a manner mechanistically similar to directed cell locomotion...
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