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Andrea Bild

Assistant Professor of Oncological Sciences and of Pharmacology and Toxicology

B.S. University of Florida, Gainsville

Ph.D. University of Colorado, Denver

Research

References

 

Andrea Bild's PubMed Literature Search

Research

My research is focused on the identification and characterization of novel genes involved in breast and lung cancer development. We also focus on the development of diagnostic and therapeutic tools to better characterize and treat cancer patients. Some examples of our research include:

1. Prediction of breast cancer susceptibility in high risk women using exon-level expression profiling. Family history is an important factor contributing to a woman’s risk of breast cancer development. This increased risk reflects the participation of inherited genetic components such as breast cancer susceptibility genes. However, many of the genetic components contributing to breast cancer remain unknown, and certain women with familial histories of breast cancer, or a mutation in the BRCA genes, live disease-free lives despite their high-risk status, while others develop breast cancer. Thus, it is clear that we lack crucial pieces of information to help define the true risk of getting breast cancer. We hypothesize that there are many undiscovered germline genetic aberrations predisposing patients to cancer that will significantly contribute to an accurate assessment of a women’s “true risk”. Our goal is to develop a clinico-genomic model capable of predicting which high-risk women will actually get breast cancer. Overall, we expect these experiments to identify the genetic changes that underlie cancer predisposition, and assist clinicians and patients in determining the appropriate preventative measures. This research involves a collaboration with Dr. Saundra Buys and Dr. Theresa Werner at the High Risk Breast Cancer Clinic at HCI.

2. Epigenetic changes and therapeutic intervention strategies in breast cancer phenotypes. Gene expression profiling studies have been used to describe and dissect the complexity of cancer phenotypes, as well as to identify opportunities for novel therapeutic strategies. Our previous breast cancer studies have used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity. We currently focus on epigenetic changes, which may arise at any stage of tumor development. Many studies highlight the contribution of epigenetic changes to tumorigenesis, and places epigenetic changes as possible seminal events for tumor initiation, and precursors for specific tumor phenotypes. We are currently generating genomic signatures of epigenetic pathways to define the signaling events that underlie different breast cancer phenotypes using over 10 large breast cancer gene expression datasets. Specifically, we will generate gene expression signatures of histone deacetylase (HDAC) and DNA methyltransferase (DMNT) pathways to uncover their role in driving breast cancer phenotypes. Further, these signatures will be linked to targeted therapies directed at epigenetic processes to uncover the relationships between drug responses and specific epigenetic processes. Together, these studies will provide a genome-wide and global view of the epigenetic changes found in breast cancer phenotypes, and the targeted agents most effective at blocking those changes. This work is funded by an R01, and involves a collaboration with Dr. Stefanie Jeffrey at Stanford University.

3. Deregulation of the phosphatidylinositol 3-kinase pathway in the airway epithelium of smokers may be an early event in the development of lung cancer. Cancer-specific signaling events may drive oncogenesis in the 10-15% of smokers who develop lung cancer. Based on the concept that cigarette smoke creates a molecular field of injury throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically-normal proximal airway epithelial cells in smokers with lung cancer. Using gene-expression signatures defined by in vitro oncogenic pathway perturbation, we observe a significant increase in the phosphatidylinositol 3-kinase (PI3K) pathway in the airway of smokers with lung cancer and in smokers with dysplastic lesions, suggesting PI3K is activated in the airway prior to tumorigenesis. Myo-inositol inhibits the PI3K pathway in vitro, and treatment of patients with myo-inositol leads to a decrease of PI3K and regression of dysplastic lesions. Our finding that oncogenic pathway deregulation in lung cancer extends to cytologically-normal airway epithelium suggests that very rapid clinical decision making could be enabled by profiling these cells, which are easily obtained during routine bronchoscopy. Our work further suggests that additional lung cancer chemoprevention trials focused on PI3K pathway activity as a target and an intermediate endpoint of efficacy are warranted. This work has been completed in collaboration with Dr. Avrum Spira at Boston University, and is supported by NIEHS funding of a U01 grant.

References