I am interested in studies of the mechanism of action of therapeutic estrogens and cytokines in normal and bone cancer cells. The studies involve in vitro and in vivo model systems and the application of genomics and proteomics tools.
- Project 1. Anti-tumor Effects of 2-Methoxyestradiol on Osteosarcoma
Osteosarcoma is a bone tumor that develops in the osteoblast cells during adolescence. A specific therapy is not yet available for this deadly disease. We have shown previously that 2-methoxyestradiol (2-ME) is effective in killing osteosarcoma cells (bone cancer cells) and not normal osteoblasts. The cell killing by 2-ME is ligand specific; the anti-osteosarcoma effects are not shared by parent estrogen, 17?-estradiol and other metabolites. We have shown that 2-ME treatment also leads to induction of interferon-? gene expression and apoptosis in human osteosarcoma cells. To understand the therapeutic potentials of 2-ME and the role of interferon pathway in osteosarcoma regulation, we are investigating the molecular mechanisms associated with 2-ME-mediated cell death in human osteosarcoma cells.
- Project 2. Receptor-independent Effects of Estrogen
The steroid hormone estrogen plays an important role in the skeletal system by regulating the activities of osteoblasts and osteoclasts. The classical effects of estrogen result in the induction of transcription (genomic action) and are mediated through estrogen receptors (ER) involving the binding of ligand-activated receptor to DNA elements. The rapid effects of estrogen are mediated through different (non-genomic) mechanisms. We have published that cytokine-regulated signal transducer and activator of transcription (Stat)-1 protein is involved in ER-independent actions of estrogen. We are further investigating the role of Stat1 protein in estrogen-dependent regulation of the skeletal system.
- Project 3. Novel Gene Delivery Techniques Using Biodegradable Polymers
Natural and synthetic polymers play an important role in localized and sustained DNA delivery systems. We are developing polymer based matrices, microspheres and nanospheres for a controlled delivery of hormones, cytokines and growth factors in bone and cartilage cells.