Description of Research Expertise
Research Interests
Transcriptional regulation
Epithelial homeostasis
Gastrointestinal carcinogenesis
Key words: gastrointestinal cancer, Krüppel-like factors, proliferation, differentiation
Description of Research
Our research is focused broadly on functional analyses of gastrointestinal epithelial proliferation, differentiation, and carcinogenesis, using both in vivo and in vitro approaches, including murine models and innovative three-dimensional tissue culture systems. To dissect the critical pathways regulating gastrointestinal epithelial homeostasis and disease, we have focused predominantly on the roles of two critical transcriptional regulators in the Krüppel-like factor (KLF) family of proteins, KLF4 and KLF5, with a particular focus on the biology of the squamous-lined esophagus. Both KLF4 and KLF5 have been implicated in key cellular process such differentiation, inflammation, stemness, and carcinogenesis in a number of tissues and cell types. Current areas of investigation in our laboratory include the functional interactions between KLF4 and the non-canonical Wnt ligand WNT5A and between KLF5 and the tumor suppressor p53. Overall, these studies seek to define the specific factors which control the balance between proliferation and differentiation in gastrointestinal epithelia and the elements which disrupt this balance during mucosal injury and carcinogenesis.
Rotation Projects
Several rotation projects are available in the laboratory based upon applicant interests. Please contact Dr. Katz directly to discuss potential projects.
Lab personnel:
Jonathan Katz, MD – Principal Investigator
Yizeng Yang, MD, PhD - Senior Research Investigator
Khvaramze Shaverdashvili, MD, PhD - Postdoctoral Fellow
Daniel Weinblatt - Research Specialist
Jinshen Wang, MD - Visiting Scholar
Divya Rao - Undergraduate Student
Administrative Assistant:
Marielle Kent
Phone: 215-898-0850
Email: hsharpe@mail.med.upenn.edu
Selected Publications
Tetreault, M.P., Yang, Y., Katz, J.P: Krüppel-like factors in cancer. Nature Reviews Cancer 13 (10): 701-13,2013.
Tarapore, R.S., Yang, Y., Katz, J.P.: Restoring KLF5 in Esophageal Squamous Cell Cancer Cells Activates the JNK Pathway Leading to Apoptosis and Reduced Cell Survival. Neoplasia 15 (5): 472-80,2013.
Yang, Y., Tarapore, R.S., Jarmel, M.H., Tetreault, M.P., Katz, J.P.: p53 mutation alters the effect of the esophageal tumor suppressor KLF5 on keratinocyte proliferation. Cell Cycle 11 (21): 4033-9,2012.
Tetreault, M.P., Alrabaa, R., McGeehan, M., Katz, J.P.: Krüppel-like factor 5 protects against murine colitis and activates JAK-STAT signaling in vivo. PLoS One 7 (5): e38338,2012.
Yang, Y., Nakagawa, H., Tetreault, M.P., Billig, J., Victor, N., Goyal, A., Sepulveda, A.R., Katz, J.P.: Loss of transcription factor KLF5 in the context of p53 ablation drives invasive progression of human squamous cell cancer. Cancer Research 71 (20): 6475-84,2011.
Tetreault, M.P., Yang, Y., Travis, J., Yu, Q.C., Klein-Szanto, A., Tobias, J.W., Katz, J.P.: Esophageal squamous cell dysplasia and delayed differentiation with deletion of Krüppel-like factor 4 in murine esophagus. Gastroenterology 139 (1): 171-81.e9,2010.
Tetreault, M.P., Wang, M.L., Yang, Y., Travis, J., Yu, Q.C., Klein-Szanto, A., Katz, J.P.: Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice. Gastroenterology 139 (6): 2124-2134.e9,2010.
Yang, Y., Tetreault, M.P., Yermolina, Y., Goldstein, B.G., Katz, J.P.: Krüppel-like factor 5 controls keratinocyte migration via the integrin-linked kinase. Journal of Biological Chemistry 283 (27): 18812-20,2008.
Yang, Y., Goldstein, B.G., Nakagawa, H., Katz, J.P.: Krüppel-like factor 5 activates MEK/ERK signaling via EGFR in primary squamous epithelial cells. FASEB Journal 21 (2): 543-50,2007.
View all publications
Academic Contact Information
421 Curie Boulevard
913 Biomedical Research Building II/III
Philadelphia,
PA
19104-4863
Phone: 215-746-7780
Patient appointments: 800-789-7366