Research Overview

To survive throughout the life of an individual, hematopoietic stem cells (or HSC), which continuously give rise to all cellular blood components, must strictly regulate their behavioral choices. These choices include self-renewal, differentiation, quiescence or death. This essential regulation of stem cells is thought to be determined at least in part by the environment, or niche, in which these cells reside. The bone forming cells, osteoblasts, have been known to support and expand HSC in vitro and co-transplantation of osteoblasts with HSC can increase engraftment rate.

Work in our laboratory and others first identified osteoblastic cells as a regulatory component in the HSC niche through genetic means. A number of molecules have since been implicated in HSC-osteoblastic interaction. In fact, it has recently become evident that cells in the osteoblastic lineage can both stimulate and limit HSC expansion, promote quiescence, coordinate HSC mobilization and, when destroyed or mutated, initiate hematopoietic dysfunction. In fact, increasing evidence points to osteoblastic lineage cells as key regulators of HSC behavior, in particular in the setting of malignant hematopoiesis and response to radiation injury.

While the HSC niche is still poorly understood, we and others have begun to demonstrate the therapeutic potential of its manipulation in animal models. Our laboratory has demonstrated that osteoblastic activation by Parathyroid Hormone (PTH) expands HSC, and improves recovery from myeloablation. Thus, the central hypothesis pursued by my laboratory is that osteoblastic cells play a central role in orchestrating microenvironmental control of the behavior of both benign and malignant HSC, and that they can be targeted for therapeutic benefit.

My laboratory therefore uniquely uses techniques that bridge bone and stem cell biology to discover the regulatory components of the bone marrow microenvironment, with the long term goal of identifying targets for therapeutic manipulation.

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