Robert A. Holmgren
Cell-fate specification during development
Our laboratory studies the process of pattern formation during animal development. Recent work has focused on the Hedgehog (Hh) signal transduction pathway and its role in the patterning of Drosophila segments and appendages. The Hh pathway has been conserved throughout the animal kingdom and is also required for the development of vertebrate appendages, floorplate and many other structures. In flies, the primary target of Hh signaling is the transcription factor Cubitus interruptus (Ci). In response to Hh signaling, cleavage of the Ci protein is blocked and Ci activates the expression of Hh target genes. We would like to understand in detail the regulation of Ci activity by signal transduction and the mechanism by which Ci acts with other factors to activate target genes. We have three major projects. The first uses a combination of genetic and structure-function studies to examine activities of various Ci protein domains. In the second, we are using genetic and molecular approaches to identify new components of the Hh signal transduction pathway, and in the third, molecular and biochemical experiments are being used to study the regulation of enhancers by Ci. Through this work, we hope to understand how cells integrate different signaling systems and have their fates specified.
Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases. Brigui A, Hofmann L, Argüelles C, Sanial M, Holmgren R, and Plessis A. Open Biology. 2015 October 7;5:150112.
Chemical map of Schizosaccharomyces pombe reveals species-specific features in nucleosome positioning. Moyle-Heyrman G, Zaichuk T, Xi L, Zhang Q, Uhlenbeck OC, Holmgren R, Widom J, and Wang, J-P. PNAS. 2013 December 10;110(50):20158-20163.
Specific Inhibition of the Transcription Factor Ci by a Cobalt(III) Schiff Base-DNA Conjugate. Hurtado RR, Harney AS, Heffern MC, Holbrook RJ, Holmgren RA, and Meade TJ. Molecular Pharmaceutics. 2012 February 6;9(2):325-333.
A Three-part Signal Governs Differential Processing of Gli1 and Gli3 Proteins by the Proteasome. Schrader EK, Harstad KG, Holmgren RA, and Matouschek A. Journal of Biological Chemistry. 2011 November 11;286(45):39051-39058.
Regulation of Ci and Su(fu) nuclear import in Drosophila. Sisson BE, Ziegenhorn SL, and Holmgren RA. Developmental Biology. 2006 June 1;294(1):258-270.
Regulation of the Drosophila transcription factor, Cubitus interruptus, by two conserved domains. Croker JA, Ziegenhorn SL, and Holmgren RA. Developmental Biology. 2006 March 15;291(2):368-381.
A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-kB. Tian L, Holmgren RA, and Matouschek, A. Nature Structural & Molecular Biology. 2005 December;12(12):1045-1053.
Ci Proteolysis: Regulation by a Constellation of Phosphorylation Sites. Lefers MA and Holmgren R. Current Biology. 2002 June 25;12(12):R422-R423.
Genetic Dissection of the Drosophila Cubitus interruptus Signaling Complex. Lefers MA, Wang QT, and Holmgren RA. Developmental Biology. 2001 August 15;236(2):411-420.
Nuclear import of Cubitus interruptus is regulated by Hedgehog via a mechanism distinct from Ci stabilization and Ci activation. Wang QT and Holmgren RA. Development. 2000 July 15;127(14):3131-3139.
View all publications by Robert Holmgren listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.