B.S. Johns Hopkins University (2011)
MD/PhD Stony Brook University (2020)
Dr. Vincent W. Yang, M.D., Ph.D.
Molecular and Cellular Biology
Pancreatic intraepithelial neoplasm (PanIN) is the most common type of precursor lesions of pancreatic ductal adenocarcinoma (PDAC). In the mouse pancreas, oncogenic Kras mutations are sufficient for spontaneous PanIN formation, which can be further expedited by cerulein-induced pancreatitis. Krüppel-like factor 5 (KLF5), a triple zinc-finger transcription factor, is differentially upregulated in pancreatic ductal adenocarcinoma (PDAC). Recent evidence shows that KLF5 is normally absent in acinar cells and is expressed in PanIN and PDAC in human tissues. The role of KLF5 in PanIN formation is unknown. To investigate whether KLF5 is required for early oncogenic Kras-driven tumorigenesis, I developed genetic engineered mouse models that combined inducible Klf5 knockout with oncogenic Kras expression in adult pancreatic acinar cells (Ptf1a-CreERTM;Klf5fl/fl, Ptf1a-CreERTM;LSL-KrasG12D, Ptf1a-CreERTM;LSL-KrasG12D;Klf5fl/fl). Klf5 knockout reduced oncogenic Kras-induced PanIN formation. Furthermore, Klf5 knockout mice failed to develop acinar-to-ductal metaplasia (ADM), a type of transformation that is triggered by pancreatitis and precedes PanIN formation. Transcriptomic analysis showed that Klf5 knockout restored normal expression of genes that were altered by oncogenic KRAS signaling. These data showed that KLF5 is required for early pancreatic tumorigenesis induced by oncogenic KRAS. Furthermore, transcriptomic profiling identified NDRG2 as a potential inhibitor of ADM.
Ping He, Kim Kramer, Peter Smith Jones, Pat Zanzonico, John Humm, Steven M. Larson, Nai-Kong V. Cheung. Two compartment model of Radioimmunotherapy delivered through Cerebrospinal Fluid. Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):334-42. Correction of Author Address in: Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):410.
Chang-Kyung Kim,** Ping He,** Agnieszka B. Bialkowska, and Vincent W. Yang. SP and KLF Transcription Factors in Digestive Physiology and Diseases. Gastroenterology 2017;152:1845–1875. **co-first authorship.
Ping He, Jong Wong Yang, Vincent W. Yang, Agnieszka B. Bialkowska. Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar to Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice. Gastroenterology 2017 Dec 14. pii: S0016-5085(17)36697-0.