David Scadden
Gerald and Darlene Jordan Professor of Medicine, Harvard University
Co-Chair, Department of Stem Cell and Regenerative Biology, Harvard University
Co-Director, Harvard Stem Cell Institute
Director, MGH Center for Regenerative Medicine
Chief, Hematologic Malignancies
MGH Cancer Center
CPZN - Room 4265A, 185 Cambridge Street
Boston, MA 02114
Tel: 617-726-5615
Fax: 617-724-2662
email: dscadden@mgh.harvard.edu
The focus of this laboratory is hematopoietic stem cell biology. We are trying to solve three problems that limit the ability of stem cells to be used more effectively as therapy. The first is stem cell number. We use a range of genetic and cell biologic approaches to understand the cell autonomous and extrinsic regulators of stem cell cycling and self-renewal. Specifically, we are using
both comparative genomics and shRNA forward screening to identify candidate mediators of the self-renewal program in hematopoietic stem cells. Second, we study stem cell localization as delivery of stem cell to specific sites is critical for their application clinically. We have identified novel mechanisms regulating the ability of the stem cell to engage its proper niche using genetic models and high resolution in vivo imaging. Third, we are deeply interested in viewing the stem cell through the microenvironment in which it resides. We have defined key elements of the stem cell niche in the bone marrow and how these
features may be modified to improve stem cell number and function. We are now applying these to in vitro models adaptable to high throughput chemical and genetic analyses to further understand niche-stem cell interactions and how they might be modified therapeutically.
Associated with the laboratory is a collaborative team emphasizing the application of basic research to the clinical care of patients with blood diseases (including AIDS) and cancer. In close concert with the clinical bone marrow transplantation and hematologic malignancies programs, we have been able to move compounds identified in the laboratory to ongoing clinical trials.
References:
- Osteoblastic cells regulate the haematopoietic stem cell niche. L. M. Calvi1, G. B. Adams, K.W. Weibrecht, J.M. Weber, D. P. Olson, M. C. Knight, R. P. Martin, E. Schipani, P. Divieti, F. R. Bringhurst, L. A. Milner, H. M. Kronenberg & D. T. Scadden. Nature, Vol 425, 23 October 2003. 841-846.
- Osteopontin is a hematopoietic stem cell niche that negatively regulates stem cell pool size. S. Stier, Y. Ko, R. Forkert, C. Lutz, T. Neuhaus, E. Gruenewald, T. Cheng, D. Dombkowksi, L. M. Calvi, S.R. Rittling, and D. T. Scadden. JEM Vol. 201, No. 11, Jun3 6, 2005. 1-12.
- Cheng T, Rodrigues N, Shen H, Yang Y, Dombkowski D, Sykes M, Scadden DT. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 2000; 287(5459):1804-8.
- Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollack MR, Brown EM, Scadden DT. Stem cell engraftment at the endostelial niche is specified by the calcium-sensing receptor. Nature. 2006 Feb 2;439:599-603. Epub 2005 Dec 28.
Immunology webpage updated 12/02/2009