|
Faculty Marc Hansen
Professor of Medicine
mhansen@nso2.uchc.edu
Areas of Interest:
My laboratory is interested in the discovery and analysis of genes
involved in the development of the bone tumor osteosarcoma. Osteosarcoma
is the most common primary tumor of bone and represents an 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.
This variation can have an influence on prognosis and can determine
treatment options. Osteosarcoma has no commonly associated benign
precursors or other morphological determinants, thus necessitating the
development of a good molecular classification system in order to
predict clinical behavior.
We are interested in examining the molecular evidence that these
variations represent distinct diseases. A better understanding of the
origin of osteosarcoma, particularly in the context of the
osteoprogenitor lineage pathways will also be useful in developing
models for this disease.
We use several approaches to address these problems. Laser capture
microdissection combined with allelotype 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 for each of the classes of osteosarcoma
to determine if they are distinct diseases. 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 examine 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.
As a product of our analysis of osteosarcoma, we have also identified
genes involved in the predisposition to several bone dysmorphology
syndromes including Hereditary Multiple Exostoses, Cornelia de Lange
Syndrome, and Paget’s Disease of Bone.
Finally, we are interested in improving treatment of osteosarcoma
patients. The survival rate of patients with osteogenic sarcoma has
greatly improved with the institution of a multidisciplinary approach
that combines multi-agent chemotherapy and limb-sparing surgery.
Presently, 80% of those patients who do not have distant metastases at
presentation will become long-term survivors. Unfortunately, this means
that approximately 20% of patients who do not have metastases at
diagnosis do not survive. Despite intensive effort and the widely
appreciated magnitude of the problem, there are currently no diagnostic
tools that can segregate, at the time of diagnosis, those children whose
osteosarcoma will respond to therapy from those whose tumor will not
respond. Our goal is to develop a molecular signature that can be
obtained at the time of diagnosis that would distinguish potential
responders from non-responders.
Visit the Center For Molecular Medicine webpage:
http://cmm.uchc.edu/index.html
Selected Publications:
Deshpande AM, Reveles X, Naylor SL, Leach RJ and Hansen MF. PHC3
acts as a tumor suppressor important in G0 transcriptional
repression. (manuscript submitted).
Bhatia P, Deshpande A, Ammerman DG, Johnson-Pais TL, Rossi JA,
Anderson DM, Unni KK, Meyers PA, Gorlick RG, Leach RJ and Hansen MF.
RANK overexpression: A link between osteosarcoma and bone remodeling (manuscript
submitted).
Johnson-Pais TL, Singer FR, Bone HG, McMurray CT, Hansen MF and Leach
RJ. (2003) Identification of a novel tandem duplication in exon 1 of the
TNFRSF11A gene in two unrelated patients with Familial Expansile
Osteolysis. J Bone Miner Res 18: 376-380.
Garg S, Hansen MF, Rowe DW and Achenie LE. (2003) An adaptive
strategy for single- and multi-cluster gene assignment. Biotechnol Prog
19: 1142-1148.
Johnson-Pais TL, Nellissery MJ, Ammerman D, Pathmanathan D, Bhatia P,
Buller CL, Leach RJ and Hansen MF. (2003) Determination of a minimal
region of loss of heterozygosity on chromosome 18q21.3 in osteosarcoma.
Int J Cancer 105: 285-288.
Seton M, Choi HK, Hansen MF, Sebalt RJ, 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: 1519-1524.
Johnson-Pais TL, Wisdom JH, Weldon KS, Cody JD, Hansen MF, Singer FR
and Leach RJ. (2003) Three novel mutations in SQSTM1 identified
in familial Paget disease of the bone. J Bone Miner Res 18: 1748-1753. |
