Karoline Briegel, Ph.D.
Associate Professor of Surgery
Description of Research
Dr. Briegel’s lab is studying the molecular mechanisms underlying aggressive triple-negative (ER-,PR-,HER2-) breast cancer and metastatic breast disease. Mounting evidence suggests that genetic programs regulating embryonic development are reactivated in these lethal cancers and may play a causal role in promoting an invasive, treatment-refractory cancer stem cell phenotype. Her lab has identified a novel embryonic transcription regulatory protein LBH, and shown that LBH is specifically over-expressed in triple-negative breast tumors as a consequence of aberrant activation of the oncogenic WNT/b-catenin signaling pathway. The WNT signaling pathway is key to self-renewal and maintenance of cancer stem cells, but the downstream effectors mediating this function of WNT are poorly understood. They have demonstrated that LBH is a direct WNT/b-catenin target gene and are currently investigating the potential role of LBH in cancer stem cell maintenance and whether pharmaceutical inhibition of LBH can be used as a new therapeutic for currently non-curable forms of breast cancer.
A second research interest in Dr. Briegel’s lab is to elucidate the function of embryonic transcription factors in the induction of a morphogenetic process called epithelial-mesenchymal transition (EMT). EMT is a prerequisite to metastasis and allows epithelial tumor cells to become more fibroblastic and migratory, resulting in tumor cell dissemination and formation of secondary tumors at distant sites. During EMT epithelial tumor cells acquire cancer stem cell-like properties. Her research has a high impact for the discovery of novel molecular cancer therapies that specifically target breast cancer stem cells, which are thought to be the culprits in tumor metastasis and recurrence.
- Discovery of a novel molecular marker for ‘Triple-negative’ breast cancer. This type of breast cancer is highly metastatic and has the worst clinical outcome because of the current lack of specific treatment options. Unraveling the characteristics and function of the tumor-marker that her lab discovered may provide new tools to diagnose and combat ‘Triple-negative’ breast cancer in the future.
- Discovery that overexpression of transcription factor TBX2, which occurs preferentially in hereditary BRCA-related breast cancers, is tumorigenic in mice. Identifying the molecular mechanisms downstream of the TBX2 pathway will shed new light into how BRCA-related breast cancers develop and progress to malignant stages.
- Identified a novel embryonic transcription regulatory protein LBH and shown that LBH is specifically over-expressed in triple-negative breast tumors as a consequence of aberrant activation of the oncogenic WNT/b-catenin signaling pathway.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):