Our general interest is to understand how cell behaviors are regulated by communications between cells in development. We approach those objectives principally by using Drosophila molecular genetics supplemented by suitable biochemical and microscopy approaches. Our efforts are focused on two major projects, described below, that are of central relevance to human medicine because (i) aberrant Hedgehog signaling is a major cause of cancer and (ii) manipulation of stem cells provides a key path for many potential cell therapies.
Zhou, Q. and Kalderon, D. (2011) Hedgehog activates Fused through phosphorylation to elicit a full spectrum of pathway responses. Dev. Cell 20: 802-14.
Marks, S.A. and Kalderon, D. (2011) Regulation of mammalian Gli proteins by Costal 2 and PKA in Drosophila reveals Hedgehog pathway conservation. Development. 138: 2533-42.
Wang, Z.A. and Kalderon, D. (2009) Cyclin E-dependent protein kinase activity regulates niche retention of Drosophila ovarian follicle stem cells. Proc. Natl. Acad. Sci. USA. 106: 21701-6.
Vied, C. and Kalderon, D. (2009) Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind. Development. 136:2177-86.
Smelkinson, M.G., Zhou, Q. and Kalderon, D (2007) Regulation of Ci-SCFSlimb binding, Ci proteolysis, and Hedgehog pathway activity by Ci phosphorylation Dev. Cell. 13: 481-495.
Zhou, Q, Apionishev, S. and Kalderon, D. (2006) The contributions of protein kinase A and smoothened phosphorylation to Hedgehog signal transduction in Drosophila melanogaster Genetics. 173: 2049-2062.
Smelkinson MG, Kalderon D. (2006) Processing of the Drosophila hedgehog signaling effector Ci-155 to the repressor Ci-75 is mediated by direct binding to the SCF component Slimb. Curr Biol. 16: 110-116.
Apionishev S, Katanayeva NM, Marks SA, Kalderon D, Tomlinson A. (2005) Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction Nat Cell Biol. 7(1): 86-92.
Price MA, Kalderon D. (2002) Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1. Cell. 108: 823-35.
Zhang Y, Kalderon D. (2001) Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature. 410: 599-604.