Dr. Wehrli’s interest is in identifying the Wnt/?-catenin signaling mechanism, and how it differs depending on cellular context and developmental stage by using the fruit fly Drosophila as a model organism. One focus of Dr. Wehrli’s research has been how the Wnt receptor subunit Arrow/LRP, which he previously identified as a novel component in the Wnt pathway, functions. As part of the receptor, Arrow functions in signal initiation; however, Arrow also has a second function in signal amplification, during which Arrow binds to and inhibits the cytoplasmic protein Axin. As a scaffold protein, Axin assembles the central regulatory complex in the Wnt pathway. Recent work has revealed that this complex, which also includes fly APC and GSK3ß, is assembled very robustly and largely resists inactivation by mutations. Ongoing work aims to determine the extent of this resilience and to model what combinations of mutations are sufficient to significantly disrupt its function. This research will provide insight into understanding genetic interactions and risk factors that lead to human disease, including cancer, osteoporosis and cardiovascular disease.
- M.S., Swiss Federal Institute for Technology, Zurich Switzerland 1989
- Ph.D., University of Zurich, Zurich Switzerland 1993
- Swiss National Science Foundation, Advanced Scientist, 1995-1997 Swiss National Science Foundation, Junior Fellowship, 1991 Roche Research Foundation, Basle (Switzerland), 1990 Julius-Klaus-Foundation, Zurich (Switzerland), 1989
Memberships and associations
- Genetics Society of America
- "Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain." Developmental Biology In: , Vol. 346, No. 1, 10.2010, p. 102-112.
- "In vivo analysis in Drosophila reveals differential requirements of contact residues in Axin for interactions with GSK3β or β-catenin." Developmental Biology In: , Vol. 337, No. 1, 01.01.2010, p. 110-123.
- "Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo." Developmental Biology In: , Vol. 320, No. 1, 01.08.2008, p. 226-241.
- "Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP." Developmental Biology In: , Vol. 306, No. 1, 01.06.2007, p. 94-111.
- "Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing." Developmental Biology In: , Vol. 293, No. 1, 01.05.2006, p. 268-283.
- "Wg/Wnt signal can be transmitted through arrow/LRP5,6 and axin independently of Zw3/Gsk3β activity." Developmental Cell In: , Vol. 4, No. 3, 01.03.2003, p. 407-418.
- "Erratum : Arrow encodes an LDL-receptor-related protein essential for wingless signalling (Nature (2000) 407 (527-530))." Nature In: , Vol. 410, No. 6830, 12.04.2001, p. 847.
- "Arrow encodes an LDL-receptor-related protein essential for Wingless signalling." Nature In: , Vol. 407, No. 6803, 28.09.2000, p. 527-530.
- "Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis." Development In: , Vol. 125, No. 8, 1998, p. 1421-1432.
- "Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila : Genetic analysis of the αPS1 integrin subunit." Development In: , Vol. 121, No. 5, 05.1995, p. 1311-1320.
- "Epithelial planar polarity in the developing Drosophila eye." Development In: , Vol. 121, No. 8, 1995, p. 2451-2459.
- "Drosophila PS1 integrin is a laminin receptor and differs in ligand specificity from PS2." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 91, No. 24, 22.11.1994, p. 11447-11451.
- "Cloning and characterization of αPS1, a novel Drosophila melanogaster integrin." Mechanisms of Development In: , Vol. 43, No. 1, 1993, p. 21-36.
- "Genetic interactions with integrins during wing morphogenesis in Drosophila." Cold Spring Harbor Symposia on Quantitative Biology In: , Vol. 57, 1992, p. 241-248.