Center for Molecular Medicine

Cell Biology Graduate Program
Skeletal, Craniofacial and Oral Biology Graduate Program

Research Interests
We are interested in understanding how components of the extracellular matrix regulate the behavior of normal bone cells and cancer cells. We use the matricellular glycoprotein osteonectin or SPARC as a paradigm for these studies, since this protein can modulate cell behavior as well as play an organizational role in the matrix. Osteonectin is widely expressed in areas of active remodeling and cellular stress in multiple organ systems. We found that osteonectin is critical for the maintenance of bone mass, and for the appropriate response of the skeleton to bone-anabolic PTH therapy. Importantly, functional SNPs (single nucleotide polymorphisms) in the 3’ untranslated region (UTR) of osteonectin are associated with bone mass in a subset of osteoporosis patients. Our present studies are focused on understanding how these SNPs regulate gene expression in vitro and in vivo. In addition, we found that a specific family of microRNAs (miRNAs) acts as negative regulators of osteonectin expression in osteoblasts. We are characterizing the mechanisms regulating the expression of these miRNAs in bone cells, and determining other genes that may also be regulated by these miRNAs. Lastly, we are interested in understanding how bone matrix composition and organization impacts the growth and survival of prostate carcinoma cells in the skeleton. Bone-metastatic prostate carcinoma cells often create an “osteoblastic response”, resulting in the deposition of a disorganized bone matrix. We will determine whether this matrix can preferentially support cancer cell survival. Our research makes use of novel in vitro and in vivo models.

Lab Rotation Projects:

Students with their own questions on how the extracellular matrix modules cell function are welcome. Projects already available in the lab include:

1. Determine how osteonectin supports the survival of bone cells.
2. Determine the impact of bone matrix organization on the behavior and survival of metastatic prostate carcinoma cells.
3. Determine how SNPs in the osteonectin 3’ UTR modulate gene expression in vivo.
4. Determine the mechanisms regulating the miR-29 family in osteoblasts.

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