Transfusion medicine has evolved from a laboratory-centered service with a focus on the serological investigation of blood to a clinical discipline that involves cellular therapies for hematopoietic stem cell transplantation and immunotherapy for infectious diseases and cancer. One of the greatest challenges of modern transfusion medicine is to improve the efficacy of cell therapies. We propose herein an extensive collaborative program entitled "Molecular mechanisms of blood cell transfusion". The long-term goal of this new program is to better understand the pathways by which transfused bone marrow or peripheral blood derived cells migrate to their intended organs/ microenvironments and carry out their distinct functions. Our hypothesis is that the efficacy of blood transfusion can be improved via modulating these pathways. The proposed program will consist of three projects and three cores. The principal investigator, project leaders and core leaders are all faculty of the Joint Program in Transfusion Medicine at Harvard Medical School. Project 1, Dr. Leslie Silberstein will study niche-induced signaling in hematopoietic stem/progenitor cell (HSC/P) transplantation. The goals of this project are to define Focal Adhesion Kinase (FAK) as a regulator of interactions between HSC/P and BM niche components, which are essential for HSC homeostasis and engraftment. Project 2, Dr. Li Chai will investigate transcriptional regulation in hematopoietic differentiation. This project will focus on the role of SALL4, a newly identified zinc-finger transcription factor, in differentiation of hematopoietic stem cells, which is a key factor for further development of ex vivo expansion of HSC and HPC cell populations and optimization of stem and progenitor cell engraftment. Project 3, Dr. Hongbo Luo will study ceil signaling in granulocyte transfusion. The ultimate goal is to identify cellular and molecular events that can improve granulocyte performance after transfusion. The three supporting cores are: Administrative Core, Animal Core, and a Flow Cytometry Core. Collectively, this program will yield significant insight and information that will directly translate into optimization of existing cell therapies and development of new ones.
The goal of this program is to better understand the molecular pathways by which transfused blood cells migrate to their intended organs and carry out their distinct functions. The proposed studies will lead to innovative approaches to enhance the transplantation efficiency of hematopoietic cells and improve the efficacy of granulocyte transfusions, which may be needed in the post-transplant period.
|Li, Zhenzhen; Ye, Zhou; Zhang, Xiaolong et al. (2016) E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice. Oncotarget 7:51815-51828|
|Wang, F; Gao, C; Lu, J et al. (2016) Leukemic survival factor SALL4 contributes to defective DNA damage repair. Oncogene 35:6087-6095|
|Bajrami, Besnik; Zhu, Haiyan; Kwak, Hyun-Jeong et al. (2016) G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling. J Exp Med 213:1999-2018|
|Tatetsu, Hiro; Kong, Nikki R; Chong, Gao et al. (2016) SALL4, the missing link between stem cells, development and cancer. Gene 584:111-9|
|Damnernsawad, Alisa; Kong, Guangyao; Wen, Zhi et al. (2016) Kras is Required for Adult Hematopoiesis. Stem Cells 34:1859-71|
|Kwak, Hyun-Jeong; Liu, Peng; Bajrami, Besnik et al. (2015) Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis. Immunity 42:159-71|
|Luo, Hongbo R; Mondal, Subhanjan (2015) Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils. EMBO Rep 16:149-63|
|Li, A; Jiao, Y; Yong, K J et al. (2015) SALL4 is a new target in endometrial cancer. Oncogene 34:63-72|
|Ciuculescu, Marioara F; Park, Shin-Young; Canty, Kimberly et al. (2015) Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoid vessels and alters hematopoiesis in vivo. Blood 125:3105-13|
|Kaunisto, Aura; Henry, Whitney S; Montaser-Kouhsari, Laleh et al. (2015) NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer. Mol Oncol 9:1140-54|
Showing the most recent 10 out of 36 publications