Zain ArifinPh.D. Student, Kolch/Zhernovkov Groups
Ciardha CarmodyPh.D. Student, Bond/Kolch Groups
Donagh EganPh.D. Student, Kolch/Brennan Groups
Soraya EppPh.D. Student, Kolch/Halasz Group
Luis Iglesias MartinezPostdoctoral Researcher, Kolch Group
Martina KreilederP.h.D. Student, Kolch Group
Aleksandar KrsticSBI Investigator
Alanah McIntoshPh.D. Student, Kolch/Bond Groups
Myriam NabhanPostdoctoral Researcher, Kolch/Brennan Groups
Annabelle NwaokoriePh.D. Student, Kolch/Fey Groups
Rashmi SharmaPostdoctoral Researcher, Kolch/Gomez Matallanas Groups
About the Group
What We Do
The Kolch group is internationally recognised for its cutting-edge research using systems approaches to understand signalling networks. The group uses computational modelling, translational medicine and omics approaches to analyse biological networks with the goal of elucidating the molecular and cellular mechanisms underlying cancer and inflammation. Current research interests focus on understanding molecular mechanisms of malignant transformation, network mediated drug resistance in cancer, and the construction of Digital Twins for personalized cancer diagnosis and therapy.
Key Research Highlights
- Discovered that Raf-1 kinase is essential for cell proliferation and malignant transformation. First use of dominant negative mutants in mammalian cells to reveal physiological and pathological functions of Raf-1. Kolch et al. Nature 349: 426 1991.
- Discovered RKIP as the first physiological inhibitor protein of the Raf-MEK-MAPK/ERK pathway. RKIP was subsequently validated as main metastasis suppressor in cancer. Yeung … Kolch, W. Nature 401, 173, 1999.
- Discovered MST2/Hippo as novel Raf-1 regulated pathway. This study identified the kinase independent regulation of MST2 as a new target for the Raf-1 kinase. O'Neill, E …Kolch, W. Science 306, 2267, 2004.
- Discovered that dynamic interactome changes in kinase substrates are linked to cell fate decisions. Von Kriegsheim, A …Kolch, W. Nature Cell Biology 11: 1458, 2009.
- Discovered intrinsic mechanisms of drug resistance mediated by network topologies. This study was one of the first to reveal that drug resistance can be network mediated and can result from dynamic network motifs. Sturm, O … Kolch, W. Science Signaling 3 (153), ra90, 2010.
- Discovered that mutant KRAS can induce apoptosis via MST2 mediated activation of p53. Activation of the MST2 pathway by mutant KRAS induces apoptosis in colorectal cancer via promoting accumulation of the tumor suppressor protein p53. Matallanas, D …Kolch, W. Molecular Cell 44, 893, 2011.
- Discovered protein interaction-based switches that coordinate signaling pathways. This work showed that protein interaction dynamics can generate switch-like pathway crosstalk and inspired the concept that protein interactions work as information processing devices. Romano, D…Kolch, W. Nature Cell Biology 16: 673, 2014.
- Co-developed methods to extract computational mechanistic models from AI/ML inferred network reconstructions. Halasz, M, Kholodenko, B, Kolch, W., Santra, T. Science Signaling 9(455): ra114, 2016.
- Developed a multi-omics data integration method that can analyze multiscale signal processing by biological networks. Santra et al…Kolch, W. Cell Reports 26: 3100-3115.e3107, 2019.
- Discovered that oncogenic RAS mutations induce the extensive rewiring of protein-protein interaction networks that re-programs signal processing and enables malignant transformation. Kennedy, S … Kolch, W. Nature Communications 11:499, 2020.
B-cell and complement signature in severe hidradenitis suppurativa that does not respond to adalimumab
Hambly R, Gatault S, Smith C, Iglesias-Martinez L, Kearns S, Rea H, Marasigan V, Lynam-Loane K, Kirthi S, Hughes R, Fletcher J, Kolch W, Kirby B. British Journal of Dermatology. 2023 Jan; 188(1), 52-63; doi: 10.1093/bjd/ljac007
Oncotherapeutic Strategies in Early Onset Colorectal Cancer
O'Reilly M, Linehan A, Krstic A, Kolch W, Sheahan K, Winter D, Mc Dermott R. Cancers (Basel). 2023 Jan 16; 15(2), 552; doi: 10.3390/cancers15020552
Dynamic regulation of RAS and RAS signaling
Kolch W, Berta D, Rosta E. Biochemical Journal. 2023 Jan 6; 480 (1): 1-23; doi: 10.1042/BCJ20220234
Targeting KRAS in Pancreatic Cancer
Cowzer D, Zameer M, Conroy M, Kolch W, Duffy A. Journal of Personalized Medicine. 2022 Nov 8; 12(11), 1870; doi: 10.3390/jpm12111870
CRABP2 - A novel biomarker for high-risk endometrial cancer
Egan D, Moran B, Wilkinson M, Pinyol M, Guerra E, Gatius S, Matias-Guiu X, Kolch W, le Roux C, Brennan D. Gynecologic Oncology. 2022 Nov; 167(2), 314-322; doi: 10.1016/j.ygyno.2022.09.020
Control of cell state transitions
Rukhlenko O, Halasz M, Rauch N, Zhernovkov V, Prince T, Wynne K, Maher S, Kashdan E, MacLeod K, Carragher N, Kolch W, Kholodenko B. Nature. 2022 Sept 14; 609, 975-985 (2022); doi: 10.1038/s41586-022-05194-y
Proteasomal down-regulation of the proapoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma
Romano D, Garcia-Gutierrez L, Aboud N, Duffy D, Flaherty K, Frederick D, Kolch W, Matallanas D. Life Science Alliance. 2022 Aug 29; doi: 10.26508/lsa.202201445
Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling
Nolan A, Aboud N, Kolch W, Matallanas D.Genes. 2021 April 10; 12(4), 553; doi: 10.3390/genes12040553
Emerging RAS-directed therapies for cancer
Conroy M, Cowzer D, Kolch W, Duffy A. Cancer Drug Resistance. 2021 April 8; 4:543-58. doi: 10.20517/cdr.2021.07
The Ins and Outs of RAS Effector Complexes.
Biomolecules. 2021 Feb 7;11(2):236. doi: 10.3390/biom11020236.PMID: 33562401
Signaling Dynamics Regulating Crosstalks between T-Cell Activation and Immune Checkpoints.
Trends Cell Biol. 2021 Mar;31(3):224-235. doi: 10.1016/j.tcb.2020.12.001. Epub 2020 Dec 30.PMID: 33388215
Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing.
Curr Opin Struct Biol. 2021 Apr;67:61-68. doi: 10.1016/j.sbi.2020.09.007. Epub 2020 Oct 24.PMID: 33126139
Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.
Int J Mol Sci. 2020 Feb 7;21(3):1102. doi: 10.3390/ijms21031102.PMID: 32046099
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D.
Nat Commun. 2020 Jan 24;11(1):499. doi: 10.1038/s41467-019-14224-9.PMID: 31980649