Pao-Tien Chuang, Ph.D., M.D.
	Hedgehog Signaling in Mammalian Embryogenesis and Postnatal Physiology
	Email: pao-tien.chuang@ucsf.edu Website: Chuang lab
Selected Publications | Complete Publications

We study the molecular mechanisms of Hedgehog (Hh) signaling in mammalian development and physiology, using 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. A combination of mouse genetics (transgenic and knockout mice), cell biology and biochemistry is utilized to address two major issues:

(1) The molecular characterization of the Hedgehog signaling pathway. We currently investigate how the Hh ligand is produced, lipidated, and transported to generate a morphogen gradient, and the molecular mechanisms by which the Hh signal is transduced. These studies serve as a paradigm for understanding lipid biology and vesicular trafficking in morphogen gradient formation, the involvement of cellular organelles, including the nucleus and the primary/motile cilia in receiving and interpreting the signal, and the evolution of developmental pathways.

(2) The role of Hedgehog signaling in various aspects of postnatal physiology and homeostasis such as stem cell maintenance and cancer formation. The postnatal roles of major signaling pathways remain poorly defined despite the widespread belief that they play a central role in postnatal development, physiology and homeostasis. Hh signaling has been implicated in regulating stem cell renewal and deregulated Hh signaling is associated with various types of cancers. This suggests an important link between Hh signaling, normal stem cell maintenance and cancer stem cell development. Understanding the molecular mechanisms by which Hh signaling regulates stem cell development and homeostasis will provide important insights into this fundamental question.

Selected Publications

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.

Wilson C.W., Chuang P.-T. 2006. New “Hogs” in Hedgehog transport and signal reception. Cell 125(3):435-8.

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.

Information last updated April 2007