David Scadden

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 have studied the regulation of the cell cycle within the stem cell compartment and have identified differentiation stage specific roles for cyclin dependent kinase inhibitors. These molecules serve to modify the size of stem and progenitor cell pools in multiple different tissue types and are modifiable targets for increasing stem cell number. 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 in the mouse. Third, we are deeply interested in viewing the stem cell through the microenvironment in which it resides. Stem cell function is largely dictated by its context and yet little is known about the features and governance of the anatomic sites where stem cells live. 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. In each case, we use genetic and cell biologic tools to define principles of cell regulation that we prioritize based on how they might influence stem cell therapies or stem cell diseases.

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. A central goal of the Scadden research team is to make a difference in the care of patients through stem cell biology.