Hedgehog signaling has been implicated in many cancers and has been shown to be a useful target for anti-cancer therapy. Previous work, including key contributions from my lab, have established that the Hedgehog protein is one of the major regulators of animal development, playing key roles in most tissues and organs in both invertebrates and vertebrates. Using newly developed reagents and methods that open new ways to study Hh signaling, the work proposed in this application will identify and characterize the processes that Hh-producing cells use to prepare and deliver Hh protein, the processes that Hh-receiving cells use to prepare for and handle its arrival, and the processes that regulate the form and activity of Ci, the transcription factor that is responsible for Hh pathway output. These issues are critical to understanding how new and better therapeutic regimens controlling Hh activity can be developed.

Public Health Relevance

Hedgehog signaling has been implicated in many cancers and has been shown to be a useful anticancer target. Work proposed in this application will identify and characterize the processes that Hh-producing cells use to prepare and deliver Hh protein, the processes that Hh-receiving cells use to prepare for and handle its arrival, and the processes that regulate the form and activity of Ci, the transcription factor that is responsible fr Hh pathway output. These issues are critical to understanding how therapeutic regimens controlling Hh activity can best be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM105987-03
Application #
8987583
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Hoodbhoy, Tanya
Project Start
2014-01-15
Project End
2017-12-31
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
3
Fiscal Year
2016
Total Cost
$271,035
Indirect Cost
$100,035
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Chen, Weitao; Huang, Hai; Hatori, Ryo et al. (2017) Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc. Development 144:3134-3144
Kornberg, Thomas B (2017) Distributing signaling proteins in space and time: the province of cytonemes. Curr Opin Genet Dev 45:22-27
Roy, Sougata; Kornberg, Thomas B (2015) Paracrine signaling mediated at cell-cell contacts. Bioessays 37:25-33
Huang, Hai; Kornberg, Thomas B (2015) Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium. Elife 4:e06114
Kornberg, Thomas B (2014) Cytonemes and the dispersion of morphogens. Wiley Interdiscip Rev Dev Biol 3:445-63
Kornberg, Thomas B (2014) The contrasting roles of primary cilia and cytonemes in Hh signaling. Dev Biol 394:1-5
Kornberg, Thomas B (2011) Barcoding Hedgehog for intracellular transport. Sci Signal 4:pe44