Elizabeth Yeh, PhD
2005 Ph.D., Duke University
Office: DDB 408
Protein kinase signaling in cancer
The overarching goal of the Yeh Lab is to examine how the deregulation of cellular signaling events results in the physiological changes that lead to human disease. We are particularly interested in elucidating how targeting protein kinase directed signaling impacts cell biological processes to become over-activated or under-activated, thereby resulting in a therapeutic effect. The Yeh Lab currently pursues this avenue of investigation by studying a novel AMPK-related protein kinase called Hormonally Up-regulated Neu-associated Kinase (HUNK) whose function we have determined to be critical in the etiology and progression of human breast cancer. However, the intracellular function of this kinase is still poorly understood.
Our findings demonstrate that Hunk regulates cellular signaling via activation of two of the Epidermal Growth Factor Receptor family members EGFR and HER2. Downstream signaling of these receptors is mediated by Hunk resulting in changes in cell survival. Our data indicates that through mechanisms that are related to EGFR/HER2 signaling, as well as those that are likely un-related, Hunk regulates cell survival by apoptosis and autophagy. Moreover, Hunk potentially feeds back to EGFR by regulating this receptor’s turnover through endocytosis. Armed with these observations, we strive to elucidate the relationship between these seemingly disparate functions of Hunk—apoptosis, autophagy, and endocytosis– that we have uncovered.
Our recent finding that Hunk participates in the two important membrane trafficking pathways: endocytosis and autophagy, is critical because these processes have been implicated not only in human cancer but a wide spectrum of human diseases including neurological disorders, pathogenic infection, cystic fibrosis, obesity and inflammation.
Recent Publications | Additional Publications
1. Abt, MA, Grek, CL, Ghatnekar, GS, and Yeh, ES (2015) Evaluating Lung Metastasis in Mouse Mammary Tumor Models by Quantitative Real-Time PCR. Journal of Visualized Experiments. In Press.
2. Williams, CB, Soloff, AC, Either, SP, and Yeh, ES (2015) Perspectives on Epidermal Growth Factor Receptor Regulation in Triple-negative Breast Cancer. Advances in Cancer Research 127:253-281.
3. Grek, CL, Rhett, JM, Bruce, JS, Abt, MA, Ghatnekar, GS, and Yeh, ES (2015) Targeting connexin 43 with α–connexin carboxyl-terminal (ACT1) peptide enhances the activity of targeted inhibitors in breast cancer. BMC Cancer. 15: 296.
4. Yeh, ES, Abt, MA, and Hill, EG. (2015) Regulation of Cell Survival by HUNK Mediates Breast Cancer Resistance to HER2 Inhibitors. Breast Cancer Research and Treatment. 149 (1), 91-98.
5. Yeh, ES, Vernon, A, Martin, H and Chodosh, LA. (2013) Tetracycline-inducible Mouse Models of Cancer. In C. Abate-Shen, K. Politi, L. Chodosh, K.P. Olive (Eds.) Mouse Models of Cancer: A Laboratory Manual. Cold Spring Harbor Laboratories Press. In press, available December 2013.
6. Yeh, ES, Belka, G, Vernon, A, Chen, CC, Jung, JJ, and Chodosh, LA. (2013) Hunk Negatively Regulates c- Myc to Promote Akt-mediated Cell Survival and Mammary Tumorigenesis Induced by Loss of Pten. PNAS. 110 (15): 6103-8.
7. Alvarez, JV, Yeh, ES, Feng, Y, and Chodosh, LA. (2012) Oncogene Addiction: Mouse Models and Clinical Relevance for Molecularly Targeted Therapies. In J. Green and T. Ried (Eds.) Genetically- engineered Mice for Cancer Research: design, analysis, pathways, validation and pre-clinical testing. (pp 527-47). New York. Springer.
8. Yeh, ES, Yang, TW, Jung, JJ, Gardner, HP, Cardiff, RD, and Chodosh, LA. (2011) Hunk is Required for HER2/neu-induced Mammary Tumorigenesis. Journal of Clinical Investigation 121 (3): 866-79.