Affiliation: University College Dublin
Halasz M, Kholodenko B, Kolch W, Santra T. Integrating network reconstruction with mechanistic modeling to predict cancer therapies. Sci Signal. 2016;9:ra114 pubmed
..We experimentally validated this prediction with colorectal cancer cell lines in culture and in a zebrafish (Danio rerio) xenograft model. ..
Santra T, Herrero A, Rodriguez J, von Kriegsheim A, Iglesias Martinez L, Schwarzl T, et al
. An Integrated Global Analysis of Compartmentalized HRAS Signaling. Cell Rep. 2019;26:3100-3115.e7 pubmed publisher
..They reveal distinct HRAS functions including the control of cell migration from the endoplasmic reticulum and TP53-dependent cell survival when signaling from the Golgi apparatus. ..
Kolch W, Fey D, Ryan C. Systems biology: old news or new stimulus for biochemistry. Essays Biochem. 2018;62:483-486 pubmed publisher
..Together this partnership is well poised to address and solve some of the major challenges in modern biology. ..
Sturm O, Orton R, Grindlay J, Birtwistle M, Vyshemirsky V, Gilbert D, et al
. The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Sci Signal. 2010;3:ra90 pubmed publisher
..These properties determine biological behavior, including activation kinetics and the response to drugs. ..
Ryan C, Brown J, Bourke E, Prendergast Ã, Kavanagh C, Liu Z, et al
. ROCK activity and the GÎ²Î³ complex mediate chemotactic migration of mouse bone marrow-derived stromal cells. Stem Cell Res Ther. 2015;6:136 pubmed publisher
..This work has identified additional potential therapeutic targets that could be manipulated to improve BMSC delivery and homing. ..
Milewska M, Kolch W. Mig-6 participates in the regulation of cell senescence and retinoblastoma protein phosphorylation. Cell Signal. 2014;26:1870-7 pubmed publisher
..We further show that Mig-6 overexpression reduces B-Raf V600E mediated pRb inactivation and preserves pRb function. ..
Jambrina P, Rauch N, Pilkington R, Rybakova K, Nguyen L, Kholodenko B, et al
. Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation. Angew Chem Int Ed Engl. 2016;55:983-6 pubmed publisher
..Our findings provide a first structure-based mechanism for the auto-transactivation of RAF and could be generally applicable to other kinases, opening new pathways for overcoming dimerization-related drug resistance. ..
Dernayka L, Rauch N, Jarboui M, Zebisch A, Texier Y, Horn N, et al
. Autophosphorylation on S614 inhibits the activity and the transforming potential of BRAF. Cell Signal. 2016;28:1432-9 pubmed publisher
..The phosphorylation of S614 is mitogen inducible and the result of autophosphorylation. These data suggest that phosphorylation at this site is inhibitory, and part of the physiological shut-down mechanism of BRAF signalling. ..
Kolch W, Fey D. Personalized Computational Models as Biomarkers. J Pers Med. 2017;7: pubmed publisher
..By populating these models with personal data, they can be highly individualized and will provide a powerful new tool in the armory of personalized medicine. ..