Research and Labs
The Brekken Laboratory
The Brekken laboratory is located in the Hamon Center for Therapeutic Oncology Research and studies tumor-host interactions with a particular emphasis on extracellular matrix (ECM) and angiogenesis. The biology of metastasis is the central focus for the lab. The lab studies how angiogenesis and ECM remodeling are key components of the metastatic cascade. Current projects are focused on the function of matricellular proteins (e.g., SPARC and fibulin-5) as regulators of ECM remodeling and angiogenesis.
Another major area of study in the lab is the development and evaluation of novel therapy for cancer with a particular focus on anti-angiogenic strategies. Vascular endothelial growth factor (VEGF) is a primary stimulant of blood vessel growth in tumors and as such is a relevant target for anti-angiogenic intervention. Currently we are studying the mechanism of anti-VEGF therapy and how inhibition of VEGF activity affects the tumor microenvironment.
The Euhus Laboratory
David Euhus, M.D., is the Marilyn R. Corrigan Distinguished Chair in Breast Cancer Surgery. His translational research program is a bridge between the Mary L. Brown Breast Cancer Genetics and Risk Assessment Clinic and the basic science laboratories of the Hamon Center for Therapeutic Oncology Research. Women with family histories of breast cancer or biopsy results showing high risk breast preneoplasia undergo a comprehensive evaluation that includes computerized risk modeling using custom software similar to the popular CancerGene program which he developed. Many women elect to participate in one of the breast epithelial cell sampling studies and undergo random fine needle aspiration biopsy and/or nipple duct lavage. Breast epithelial cells are evaluated for cytological signs of high risk preneoplasia and the DNA from these cells is tested for promoter region methylation of tumor suppressor genes (RASSF1A, APC, RAR -b, H-Cadherin, Cyclin D2, or TWIST) and for amplification of activating oncogenes such as Her -2/neu, Cyclin D1 and C-MYC. The combination of extensive epidemiological breast cancer risk information and sophisticated analysis of biomarker expression in benign breast epithelium allows rapid screening of potential biomarkers in the pursuit of accurate individualized breast cancer risk assessment, and is contributing to our knowledge of the molecular changes responsible for malignant transformation of breast epithelium.
Because genomic instability appears to be a central feature of breast cancer, the laboratory is also investigating individual differences in DNA repair response after exposure to DNA damaging agents that can be found in the environment such as benzo[a]pyrene and radiation. These studies involve short term culture and characterization of myoepithelial and luminal epithelial breast cells as well as extensive genotyping of DNA repair enzymes.
- A randomized prospective double blind trial to identify biomarkers in breast epithelium that are modulated by tamoxifen but not placebo.
- Markers of growth dysregulation in breast epithelium obtained by random fine needle aspiration biopsy in women at high risk for breast cancer.
- Serial Evaluation of Ductal Epithelium by Nipple Duct Lavage.