Overview of Research Projects
Ongoing studies in our lab are primarily focused on a subtype of breast cancer that is highly aggressive, resistant to treatment, and associated with poor prognosis. This subtype, known as estrogen receptor (ER) negative breast cancer, is more likely to affect young women and women of African descent. Women with mutations in the breast cancer gene (BRCA1) are also more likely to be diagnosed with ER negative breast cancer. However, little else is understood about ER negative breast cancer, including its genetic and environmental risk factors, appropriate screening methods, and effective treatments. Information gathered from the following studies in our lab would ultimately help develop more effective and less harmful methods to prevent, screen, and treat all types of breast cancer. BRCA Mutations in Populations of African Ancestry Despite having lower rates of breast cancer than Caucasians, African Americans are more likely to be diagnosed with breast cancer at an earlier age and more likely to die from the disease. In search of a genetic explanation for these disparities, our lab was the first to describe recurrent BRCA1 mutations in extended African American (AA) families with breast cancer. Studies focused on the prevalence and spectrum of genetic alterations in BRCA1/2 genes in African American and Nigerian populations are ongoing in our Center. This research is helping provide better cancer risk assessment for patients of African ancestry and reveal ancient gene variants that may shed light on these gene functions in all patients. |
OUR RESEARCH IS GENEROUSLY FUNDED BY The Breast Cancer Research Foundation The Doris Duke Charitable Foundation The Entertainment Industry Foundation Dr. Ralph and Marian |
Breast Cancer Related Protein Function
We are also studying how the vascular endothelial growth factor (VEGF), an important protein involved in the growth of blood vessels, affects breast tumor progression. Growth and metastasis of tumors require adequate oxygen and nutrients supplied by blood vessels. Thus, the development of new blood vessels is a fundamental requirement for tumor growth and is stimulated by VEGF. Ongoing investigations in our lab examine how some forms of VEGF promote breast tumor development and others inhibit tumor progression. We are also interested in exploring clinical applications of these investigations, including the use of VEGF as a clinical biomarker for breast tumor progression. Such research will provide a scientific basis for the development of VEGF-based personalized treatment strategies and possibly VEGF-targeted therapies.
Epigenetic Regulation of BRCA1 Promoters
BRCA1 expression is frequently reduced in breast cancer by promoter methylation, but the mechanism is largely unknown. Ongoing work in our lab is focused on examining the correlation between methylation profile and gene expression in cancer cell lines and patient samples. In addition, we are interested in developing therapies that use demethylating drugs. Exploring the mechanism of BRCA1 promoter methylation may contribute to an understanding of the BRCA1 down-regulation that is directly related to breast tumor initiation, progression, and treatment.
Role of Secondary Genetic Alterations in Cancer Development
Other research focuses on secondary genetic changes in tumors with BRCA1 dysfunction. We are specifically evaluating the differential contribution of oncogenes such as HER2 and MYC in relation to BRCA1 inactivation status. Using high throughput fluorescent in situ hybridization (FISH) on formalin-fixed paraffin-embedded breast tumor tissues, we showed that in spite of similarity in clinical pathology, BRCA1-mutated and HER2 (ErbB2)-amplified tumors progress through distinct molecular pathways. In addition, we found that the aggressive features of BRCA1-deficient tumors appear related to amplification of the MYC oncogene.