Anne Delany Ph.D.
Investigator,
Center for Molecular Medicine
Assistant Professor of Medicine
Email: adelany@uchc.edu
Phone: 860-679-8730
Fax: 860-679-7639
Research Interests
- Function and Regulation of Osteonectin/SPARC in Bone
- Regulation of Osteoblast Gene Expression by
MicroRNAs
- Bone Matrix-mediated Regulation of Gene Expression
in Prostate Cancer Cells
We are interested in understanding how components of the
bone matrix regulate the behavior of normal bone cells and
metastatic cancer cells. Our work focuses on the
matricellular glycoprotein osteonectin or SPARC. It is
the most abundant non-collagenous matrix component of the
bone and it 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.
Further, we found that 3 SNPs (single nucleotide
polymorphisms) in the 3’ untranslated region (UTR) of
osteonectin are associated with bone mass in a subset of
osteoporosis patients. Our in vitro studies indicate
that these SNPs can differentially regulate gene expression.
Our present studies are focused on understanding how these
SNPs regulate gene expression in vitro and in vivo, using a
knock-in mouse strategy. 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:
- Determine how SNPs in the osteonectin 3’ UTR
modulate gene expression in vivo, by analyzing the
skeletal phenotype of 3’ UTR is knock-in mice.
- Determine the mechanisms regulating the miR-29
family in osteoblasts.
- Identify other miR-29 targets in osteoblasts and
osteoclasts.
- Determine the impact of bone matrix organization on
the behavior and survival of metastatic prostate
carcinoma cells.
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