My research laboratory focuses mainly on the pathogenesis of prostate cancer bone metastases. Prostate cancer has clinical features unique among adult solid tumors, including high tropism for bone and the osteoblastic nature of most bone metastases. Yet little is known about the dynamic prostate cancer–bone cell interactions essential to growth of metastatic cells in bone. We investigate the nature of prostate cancer cell – osteoblast interactions and their exacerbation of tumor progression in bone. Focusing on tumor–bone interactions, not on biologic changes in tumor cells alone as most "standard" studies do, is a unique aspect of my research program.

Lack of clinically relevant models of prostate cancer has substantially limited this type of study. We thus developed such models and use them to enhance our understanding of molecular interactions required in metastasis.

Fibroblast growth factor 9 (FGF9) and FGF receptor 1 (FGFR1) are likely mediators of prostate cancer growth in bone; we confirmed their aberrant expression in human prostate cancer. We are now studying the molecular mechanism underlying FGF-mediated prostate cancer growth in bone and whether prostate cancer cells activate classic FGFR downstream target genes (e.g., FRS2alpha/MAPK) in bone. These studies use the in vitro and in vivo models we developed.

Prostate cancer cells induce osteoblast proliferation and differentiation. Specifically, prostate cancer cells activate the Wnt canonical pathway and induce expression of the transcription factor Runx2 in osteoblasts. These findings suggest that prostate cancer cells induce new bone formation by activating true bone-development programs in osteoblasts.