Research
Our laboratory is focused on basic and translational studies in bone biology and bone marrow hematopoietic and malignant niches. Several basic (Bench) and translational (Bedside) projects are highlighted below.
Bench
Osteoprogenitors and bone marrow hematopoietic niches
The differentiation of hematopoietic cells from hematopoietic stem cells (HSCs) in the bone marrow is dependent upon the surrounding microenvironment, or niche. Cells of the osteoblast lineage are an important component of bone marrow hematopoietic niches. We have found that signaling downstream of the parathyroid hormone receptor PPR in osteoblast progenitors is critical for B cell development.
Commitment and differentiation of the osteoblast lineage
Osteoporosis is one of the most common degenerative diseases of aging. Bone-forming osteoblasts are derived from mesenchymal stem/progenitor cells, and we are interested in the pathways that guide the commitment of mesenchymal progenitor cells into osteoblasts rather than fat-laden adipocytes.
Osteogenic differentiation of pluripotent stem cells
An unlimited source of bone-forming osteoblasts would have exciting implications for regenerative medicine, disease modeling and drug screening. We are working on protocols to differentiate osteoblasts from pluripotent stem cells.
Cancer cells and the skeletal microenvironment
The skeleton is one of the most common sites of metastatic spread for many common cancers. In addition, many cancer patients are at the risk for bone loss due to chemotherapy and hormonal deprivation. We have found that recombinant PTH decreases breast cancer metastases to bone and are working to understand the mechanisms.
Bedside
Effects of bone medications on blood cells
Since osteoblasts play a supporting role in the differentiation of hematopoietic cells, diseases and medications that target osteoblasts may impact hematopoiesis. We have shown that teriparatide can increase circulating hematopoietic stem cells in women with osteoporosis.
Interactions between bone health and blood counts
We have found that in older men, rapid bone loss is associated with changes in blood counts and especially anemia. We have also shown that anemia is associated with an increased risk of fractures.