Jianhang Jia, Ph.D.

Associate Professor
Molecular & Cellular Biochemistry

Office: 859-323-6236
Email: jji223@uky.edu

Graduate Students and Postdoc Positions are available, please contact Dr. Jia - jji223@uky.edu.

Introduction

The goal of our research is to understand the molecular mechanisms of the Hedgehog (Hh) signaling pathway, which governs the pattern formation, cell proliferation and differentiation. Malfunction of Hh signaling pathway induces different types of cancers in many tissues. The study in our laboratory focuses on the components that participate in the Hh signal transduction.

Hedgehog Signaling

Hh pathway consists of two transmembrane proteins, Patched (Ptc) and Smoothened (Smo), and a zinc-finger transcription factor, Cubitus interruptus (Ci), that transduces Hh signal into the nuclei. Without Hh stimulation, Ptc inhibits Smo thus allowing Ci processing to generate its truncated form which enters the nuclei and blocks downstream genes. Upon Hh stimulation, the inhibition of Ptc on Smo is blocked and Smo transduces the Hh signal to downstream blocking Ci processing. Full-length Ci is translocated to the nuclear and turns on downstream genes. We are investigating the mechanism of Smo transducing Hh signal and how Hh gradient can be translated into different thresholds of downstream gene expression.

Selected Publications

Hongge Jia, Yajuan Liu, Wei Yan, and Jianhang Jia. PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci phosphorylation. Development 136, 307-316, 2009.

Yajuan Liu, Xuesong Cao, Jin Jiang, and Jianhang Jia. Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation. Genes and Development 21(15): 1949-1963, 2007.

Jianhang Jia and Jin Jiang. Decoding the Hedgehog signal in animal development. Cell. Mol. Life Sci. 63: 1249–1265, 2006.

Jianhang Jia, L. Zhang, Q. Zhang, Chao Tong, Bing Wang, F. Hou, Kazuhito Amanai, Jin Jiang. Phosphorylation by Double-Time/CKlepsilon and CKlalpha Targets Cubitus Interruptus for Slimb/beta-TRCP-Mediated Proteolytic Processing. Developmental Cell 9(6):819-30, 2005.

Wensheng Zhang, Yun Zhao, Chao Tong, Gelin Wang, Bing Wang, Jianhang Jia, and Jin Jiang. Hedgehog-Regulated Costal2-Kinase Complexes Control phosphorylation and Proteolytic Processing of Cubitus Interruptus. Developmental Cell 8:267–278, 2005.

Jianhang Jia, Chao Tong, Bing Wang, Liping Luo and Jin Jiang. Hedgehog signaling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature 432:1045-1050, 2004.

Jianhang Jia, Wensheng Zhang, Bing Wang, Richard Trinko and Jin Jiang. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes and Development 17:2514-2519, 2003.

Jianhang Jia, Chao Tong, and Jin Jiang. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its carboxyl-terminal tail. Genes and Development 17:2709-2720, 2003.

Jianhang Jia, Kazuhito Amanai, Gelin Wang, Jiong Tang, Bing Wang and Jin Jiang. Shaggy/GSK3 anatagonizes Hedgehog signaling by regulating Cubitus interrupus. Nature 2002, 416:548-552.
 

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