Areas of Interest
My laboratory is interested in two areas of bone disease. The
first is the genetic origins of the bone tumor osteosarcoma.
Osteosarcoma is the most common primary tumor of bone and
represents in important opportunity for interaction between
basic and clinical research.
Osteosarcoma is highly variable in its presentation with
numerous subtypes based on the histology, age of onset and site
of occurrence. We are interested in examining the molecular
differences between these subtypes particularly in the context
of the osteoprogenitor lineage pathways from which these tumors
arose.
The second area of interest in my laboratory is the genetic
origins of Paget’s disease of bone. Paget’s disease is a focal
disorder of bone remodeling that leads to overgrowth of affected
bone, which in rare cases progresses to osteosarcoma. It is the
second most common metabolic bone disease after osteoporosis
affecting 1-3% of the U.S. population after age 50.
Approximately 20% of Paget’s patients have a positive family
history for the disease. Although relatively common, the
etiology of Paget’s disease has so far eluded researchers. Our
data suggests a model in which a subset of cells might be
responsible for the pagetic phenotype in the affected bone. My
laboratory is interested in learning what genetic events are
critical to the initiation and progression of this disease.
We use several approaches to address these problems. Laser
capture microdissection combined with allelotype discrimination
analysis, high throughput genotype analysis, comparative and
arrayed BAC genome hybridization, cDNA microarray and mass
spectroscopy analysis allow us to compare genomic and expression
profiles. We then validate our analysis using tissue
microarrays, quantitative PCR and other high sample throughput
methods. Finally, we use in situ hybridization and
immunohistochemistry to validate the expression profiles of our
candidate genes. We have also begun to develop transgenic mouse
models for osteosarcoma to test its relationship with normal
bone development.
Selected Publications
Kong C and Hansen MF. Biomarkers in osteosarcoma. (2009) Expert
Opinion on Medical Diagnostics 3: 13-23. Merchant A, Smilewska
M, Patel N, Akunowicz JD, Saria EA, Delaney JD, Leach RJ, Seton
M and Hansen
MF. (2009) Somatic mutations in SQSTM1 detected in affected
tissues from patients with sporadic Paget disease of bone. J
Bone Mineral Res 24: 484-494.
Deshpande AM, Akunowicz JD, Reveles X, Patel BB, Saria EA,
Gorlick RG, Naylor SL, Leach RJ and Hansen MF (2007) PHC3, a
component of the hPRC-H complex, associates with E2F6 during G0
and is lost in osteosarcoma tumors. Oncogene 26: 1714-22. Xu
Z, Choudhary S, Voznesensky O, Mehrotra M, Woodard M, Hansen M,
Herschman H and Pilbeam C. (2006) Overexpression of COX-2 in
human osteosarcoma cells decreases proliferation and increases
apoptosis. Cancer Res 66: 6657-64. Hansen MF, Seton M and
Merchant A (2006) Osteosarcoma in Paget’s Disease of Bone. J
Bone Miner Res Suppl. 2: P58-63. Seton M, Choi HK, Hansen MF,
Sebalt RJ and Cooper CC (2003) An analysis of environmental
factors in familial versus sporadic Paget’s disease of bone -
The New England Registry for Paget’s disease of bone. J Bone
Mineral Res 18:1519-24. Rev. 3/09 |
