Ongoing projects
Radiosensitizing Studies
Our research lab utilizes kinome screens to identify novel targets for the treatment of aggressive breast cancers, including triple-negative breast cancer. The lab is also interested in the mechanisms of treatment resistance that include modulation of breast tumor initiating cells, breast cancer stem cells, and understanding novel layers of cancer biology, including the role of long non-coding RNA and the immune system in triple-negative breast cancer.
Our laboratory focus is “bench to bedside” research that includes basic mechanistic studies, translational preclinical studies, and clinical research that is funded by the NIH, NCI, DOD, BCRF, Komen for the Cure Foundation, and the Hope Foundation. Current focuses include interest in targeted therapies including PARP-inhibitors, CDK 4/6 inhibitors, and androgen receptor antagonists as agents for radiosensitization. These preclinical studies have been foundational to completed or open clinical trials evaluating these combinations in women with aggressive forms of breast cancer.
Clinical trials resulting from our labs research:
- Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, Node Positive, HR+/HER2- Breast Cancer
- Radiation Therapy With or Without Olaparib in Treating Patients With Inflammatory Breast Cancer
- Veliparib With Radiation Therapy in Patients With Inflammatory or Loco-regionally Recurrent Breast Cancer
- The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. (T-REX)
Transcriptomic Signatures to Guide Radiation Decisions in the Clinic:
Personalized Medicine for Breast Cancer
Recent advances in gene expression profiling have allowed for a more sophisticated understanding of the biology of breast cancers. These advances led to the development of molecular signatures that now allow clinicians to more individually tailor recommendations regarding the utility and necessity of systemic therapies for women with breast cancer. Similar, though slower, progress is being made in the development of molecular signatures predictive of radiation response and necessity for women with breast cancer. Our groups is developing some of the first radiation specific signatures to be used clinically and these prognostic and predictive signatures to guide radiation treatment decisions for women with invasive breast cancer.
Understanding the mechanisms of radioresistance in breast cancer
Radiation therapy is a mainstay treatment for breast cancer, effective at reducing rates of locoregional recurrence and improving overall survival for many patients. However, radiation therapy alone is not as effective for patients with triple-negative breast cancer. To identify potential targets for combination therapies, we are using a genome-wide CRISPRi screen to knock down genes in triple-negative breast cancer cell lines. This will allow us to identify genes which are critical to radiation survival in these cell lines, which we can further investigate as potential radiosensitizers.
Understanding the mechanism of metastasis in breast cancer
Triple-negative breast cancer has an earlier age of onset and higher rate of metastasis relative to other breast cancer subtypes. As metastasis is involved in over 90% of cancer deaths, we want to identify the mechanisms that enable successful metastasis in triple-negative breast cancer. In this project, we are using macsGESTALT, a dynamic, inducible lineage tracing system that leverages CRISPR-editable barcodes, to track breast cancer cells and how a lineage changes as it proceeds through the different stages of metastasis in a mouse model. This will allow us to identify transcriptional and regulatory changes that occur at each different stage. We hypothesize that the epithelial-mesenchymal transition (EMT) will play a role in cells exiting the primary tumor, while its reverse process, the mesenchymal-epithelial transition (MET), will be involved in colonizing metastatic sites. We hope to use this knowledge to design treatments that will allow us to prevent or reverse metastatic spread.
