Ling Qin, Ph.D.

Description of Research Expertise

Area of Expertise:

Bone metabolism, cancer bone metastasis, stem cell biology, and signal transduction


Area of Special Interest:

The adult human skeleton continuously undergoes remodeling, namely, being resorbed by osteoclasts and renewed by osteoblasts. The maintenance of the skeleton requires the coordinated activities and constant generation of these cells. Disruption of this coordination underlies many bone diseases, such as osteoporosis and cancer-associated bone loss. These diseases cause great morbidity and mortality in the elderly and in the bone metastasized cancer patients and therefore are a major public health problem worldwide. A variety of growth factors and hormones play important roles in bone metabolism. Our laboratory focuses on a family of epidermal growth factor (EGF)-like ligands and their cognate receptors and uses a combination of molecular, biochemical, imaging and animal techniques to understand the molecular mechanisms of how this signaling pathway network regulates bone metabolism.

Ongoing research projects:

1. The role of EGF receptor (EGFR) signaling in bone development and parathyroid hormone (PTH) treatment of osteoporosis.
PTH, a major mediator of calcium homeostasis and bone remodeling, is one of the most effective drugs for osteoporosis treatment. Intermittent administration of PTH greatly stimulates bone formation by acting through its receptor on the osteoblasts. Recently, our research identified that the expression of amphiregulin, one of EGF-like ligands, is rapidly and highly stimulated by PTH in osteoblastic cells. This project attempts to understand the physiological function of EGFRsignaling and whether this signaling pathway mediates PTH’s anabolic actions on bone.

2. The role of EGFR signaling in the proliferation, differentiation and localization of bone marrow stromal stem cell (BMSSCs).
Bone marrow stromal stem cells, also called mesenchymal stem cells, are adult stem cells residing in the bone marrow cavity. They are multipotent progenitors for osteoblasts, adipocytes, and chondrocytes in bone. Numerous studies also suggest that these cells can give rise to muscle fibers, hepatocytes, endothelial cells and even neural tissue in vitro. Hence, BMSSCs are a promising tool for regenerative medicine and gene therapy. Emerging results suggest that EGFR signaling stimulates BMSSC proliferation but can have conflicting effects on the cells’ multidifferentiation. Interestingly, our research identified EGF-like ligands as potent chemotactic factors for BMSSCs. The goal of this project is to delineate the function of EGFR signaling in the proliferation, multidifferentiation and localization of BMSSCs. This research will also provide interesting insight into whether EGF-like ligands could be used as one of the substitutes for serum in ex vivo BMSSC expansion, which will be useful for stem cell transplantation.

3. The role of EGFR signaling in cancer bone metastases.
Bone is the preferred metastasis site for many cancer cells. For example, breast cancer metastasizes to bone in greater than 80% of patients with advanced disease and leads to bone pain, fractures, hypercalcemia, and/or nerve compression. In the past several decades, enormous efforts have been focused on identifying tumor-derived factors that modify bone structures but yet the incomplete understanding of the underlying mechanism hinders the development of effective therapies that would help breast cancer patients. Using a coculture system containing bone marrow macrophage and osteoblastic cells, we recently found that EGF-like ligands stimulate osteoclastogenesis via acting on osteoblastic cells. We are currently testing the hypothesis that tumor-derived EGF-like ligands contribute to osteolytic lesions caused by cancer bone metastasis. Since several anti-EGFR agents are currently drugs for cancer treatment, this project will not only reveal a possible mechanism for cancer bone metastases, but also have important clinical implications.