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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL095489-04
Application #
8511787
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Mondoro, Traci
Project Start
2010-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$1,935,701
Indirect Cost
$547,832
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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