Biomedical Sciences Graduate Program | University of California, San Francisco

Pao-Tien Chuang, MD, PhD
Hedgehog Signaling in Mammalian Embryogenesis and Postnatal Physiology

Selected Publications | Complete Publications

phone	(415) 514-0667
email	pao-tien.chuang@ucsf.edu
additional websites	Lab Website Tetrad Graduate Program Cardiovascular Research Institute
secondary research affiliation	Tissue/Organ Biology & Endocrinology

We study the molecular mechanisms of Hedgehog (Hh) signaling in mammalian development and physiology, using the mouse as a model system. The Hh pathway plays a key role in many aspects of embryonic development, and dysregulation of Hh signaling is associated with human congenital anomalies and cancers. We utilize a combination of mouse genetics (transgenic and knockout mice), cell biology and biochemistry to address three major issues:

(1) The molecular characterization of the Hedgehog signaling pathway.
We currently investigate how the lipidated Hh ligand generates a morphogen gradient and the molecular mechanisms by which the Hh signal is transduced.

(2) The role of Hedgehog signaling in various aspects of postnatal physiology and homeostasis, including stem cell maintenance and cancer formation.
We investigate regulation of neural and pulmonary stem cells by Hh signaling, and how aberrant Hh signaling leads to brain tumors and lung cancers.

(3) Lung branching morphogenesis as a model system to study signal integration during mammalian embryogenesis.
With the availability of organ culture, the stereotyped branching process and the ease of following the branching process, the lung is an attractive system to address the molecular mechanisms of branching morphogenesis. This process involves epithelial-mesenchymal interactions and plays an essential role in the formation of many other organs.

Selected Publications

Chuang P.-T., McMahon A.P. 1999. Modulation of vertebrate Hedgehog signaling through the induction of a Hedgehog-binding protein. Nature 397(6720):617-21.

Kawakami T., Kawcak T., Li Y.-J., Zhang W., Hu Y., Chuang P.-T. 2002. Mouse dispatched mutants fail to distribute Hedgehog proteins and are defective in Hedgehog signaling. Development 129(24):5753-65.

Chuang P.-T.; McMahon A.P. 2003. Branching morphogenesis of the lung: new molecular insights into an old problem. Trends Cell Biol 13(2):86-91.

Chuang P.-T., Kawcak T., McMahon A.P. 2003. Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding Protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes Dev 17(3):342-7.

Chen M.-H., Li Y.-J., Kawakami T., Xu S.-M., Chuang P.-T. 2004. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev 18(6):641-59.

Chen M.-H., Gao N., Kawakami T., Chuang P.-T. 2005. Mice deficient in the Fused homolog do not exhibit phenotypes indicative of perturbed Hedgehog signaling during embryonic development. Mol Cell Biol 25(16):7042-53.

Mak K.K., Chen M.-H., Day T.F., Chuang P.-T., Yang Y. 2006. Wnt/ß-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development 133(18):3695-707.

Gerber A.N., Wilson C.W., Li Y.-J., Chuang P.-T. 2007. The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation. Oncogene 26(8):1122-36.

Chen M.-H., Wilson C.W., Chuang P.-T. 2007. SnapShot: Hedgehog Signaling Pathway. Cell 130(2):386.

Wilson C.W., Nguyen C., Chen M.-H., Yang J.-H., Gacayan R., Chen J.-N., Chuang P.-T. 2009. Fused has evolved divergent roles in vertebrate Hedgehog signaling and motile ciliogenesis. Nature 459 (7243):98-102. Epub 2009 Mar 22.

Wilson C.W., Chen M.-H., Chuang P.-T. 2009. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS ONE 4(4):e5182. Epub 2009 April 13.

Chen M.-H., Wilson C.W., Li Y.J., Lu C.-S., Gacayan R., Zhang X., Hui C.-c., Chuang P.-T. 2009. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev 23(16):1910-28.

information last updated August 2009