Our lab primarily
focuses on the identification and characterization of molecular alterations
leading to the development of solid cancers, particularly breast cancer.
Study of these changes at both the genetic and protein level will lead to
the identification of potential diagnostic, prognostic, and predictive
markers. Such markers may also prove useful as potential therapeutic targets.
Cancer results from
the progressive accumulation of genetic alterations. In some organ systems
(i.e. colon and cervix), it has been demonstrated that increasing degrees
of genetic perturbation are also accompanied by increasing degrees of
histologic dysplasia. Other tissues are less accessible, making definitive
establishment of these links more difficult. In the breast, the appearance
of certain pre-neoplastic and pre-invasive lesions has been linked to the
development of invasive cancer through an increase in relative risk.
However, it has yet to be clearly established whether or not all these
lesions have the potential to progress to invasive breast cancer, or are
merely markers of increased risk. One such lesion, duct carcinoma in situ (DCIS), is being
increasingly detected by mammography.
It is critical to
localize particular genetic aberrations to specific cells, thereby enabling
a correlation between observed histology and genetic changes. Many
molecular techniques, both traditional and advanced, are available to
investigate possible relationships. Advances in tissue microdissection and
PCR technologies have made it possible to study molecular alterations in
small, histologically defined lesions, such as DCIS. Laser assisted
microdissection of tissues, fluorescence in
situ hybridization (FISH) analysis, and image analysis of
histological sections are all technologies employed by our group. A
significant amount of work is conducted in our lab using gene microarray
"chips" to identify genes and chromosomal regions which are
amplified or deleted in the transition from pre-invasive to invasive
cancer. We also employ mouse models to investigate the many facets of
mammary cancer. Other current projects include identification of molecular
alterations in common between synchronous primary breast cancers, and the
role of telomere length and mitochondrial mutations in the progression of
DCIS.
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