We have focused our efforts on gene expression and regulation of extracellular matrix proteins in bone development. Using transgenic mouse model we were the first in reporting the expression of bone sialoprotein (BSP) promoter in a tissue specific and developmentally regulated fashion. We have also, for this first time, established a unique and versatile TVA (a chicken retroviral receptor) model to study the effects of a variety of regulatory factors, including “master genes” Runx2/Cbfa1 and osterix (Osx) in vivo during deferent stages of bone development. We have recently identified the signal transduction pathway of BSP in osteoclast formation and bone resorption.
        We are currently studying cell differentiation in bone regeneration and tissue engineering. We have used bone marrow stem cells to regenerate calvarial, femoral and periodontal alveolar bones in which both gene-therapy and cell-based approaches have been applied. Using specific transgenic models we are able to identify the migration, differentiation and fate of transplanted cells in tissue engineering in live animals.
        We have first cloned, sequenced and characterized hamster BSP and osteopontin genes and reported their expression in carcinogensis. We have started a series of investigations in determining the effects and mechanisms of extracellular matrix proteins and growth factors in promoting bone metastasis of human breast cancer cells. In these experiments, intracardiac injection of tumor cells in nude mice, siRNA delivered by lentivira vectors, and DNA antisense strategies have been used.
        The tools and methods we routinely employ in our lab include Northern, Southern, Western and in situ hybridizations, transgenic animal model, animal surgery and experimental pathology, tumorigenesis, histomorphometry, immunohistochemistry, luciferase assays, TVA viral receptor model , cell and tissue cultures, signal transduction pathway.