Projects

Osteoimmunology

We study the reciprocal interactions between bone cells (osteoclasts and osteoblasts) and immune cells (T cells, B cells, macrophages and neutrophils). Our focuses are to study the mechanisms by which aging T cells polarize inflammatory macrophages expressing TGFβ1 (i-Macs^Tβ1), which induces TRAF3 lysosomal degradation in T cells and osteoblasts to cause immunosenescence and to inhibit bone formation in age-related osteoporosis. Our goal is to develop a new therapeutic approach with dual anabolic and anti-resorptive effects for the prevention and treatment of osteoporosis.

Studies of breast cancer metastasis

Our focuses are to study how TNF and LPS regulate tumor-associated macrophage (TAMs) to promote the progression of metastatic breast cancer by stimulating the expression of inhibitor of apoptosis proteins (IAPs), a class of E3 ubiquitin ligase, and to develop a novel adoptive macrophage transfer approach for the treatment of metastatic breast cancer in combination with an IAP antagonist

Development of novel bone-targeted therapeutic agents for the treatment of bone diseases with bone loss

Based on the high affinity of bisphosphonate to bone, we synthesize a variety of novel bone-targeted agents by chemically linking an agent, such as hydroxychloroquine, maraviroc and plerixafor, to a low active bisphosphonate, aiming to treat bone diseases with bone loss.

The role of B cells in age-related osteoporosis 

The major goal of this project is to investigate the role of NF-κB signaling in the formation of osteoclasts and osteoblasts focusing on the mechanisms whereby a novel subset of RANKL-expressing B cells, which are increased in the bone marrow during aging as a consequence of increased NF-κB-induced expression of CCL12 by mesenchymal progenitor cells, cause age-related bone loss.