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 in the figures.
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 lymphocyte development.
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.
The identification of pluripotency factors that can convert somatic cells into induced pluripotent stem cells (iPSCs) has transformed the field of stem cell biology, with exciting implications for regenerative medicine, disease modeling and drug screening. We are working to differentiate iPSCs into osteoblasts, and are testing their functional capacity in a model of skeletal complementation.
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 seek to understand how teriparatide alters the metastatic niche in bone.
Many chronic diseases are associated with decreased bone density. As one example, patients receiving bone marrow transplantation are at risk for bone loss due to cancer treatment, hypogonadism, and immunosuppressive agents. Preventive measures to maintain bone density in patients undergoing bone marrow transplantation should significantly impact their quality of life.
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.