The MAPK cascades are evolutionary conserved signalling pathways that play a significant role in many cellular processes, including proliferation, differentiation, apoptosis, learning and memory, and angiogenesis. My research is focussed on the mechanisms that determine the specificity of cellular signalling in order to ensure that the outcome of the process accurately reflects the incoming signals received by the cell in a specific environment. This includes investigations into the regulation of signalling dynamics, particularly regarding those mechanisms that confer temporal and spatial control over the MAPK pathways. I am also interested in elucidating the crosstalk between different signal transduction pathways and their contribution to signal modulation. Finally, I am investigating the re-programming of cellular signalling pathways in disease processes and the role of this plasticity in drug resistance.
A recent area of my research has been the role of the ERK5 MAPK pathway in angiogenic processes. Both impaired as well as excessive growth of blood vessels contribute to a number of diseases and influence the efficacy of drug treatment. The main aims of this research are to investigate the molecular mechanisms by which the ERK5 MAPK pathway maintains the health of endothelial tissues. Advances in our understanding of angiogenic processes resulting from this research will help to develop better cardio-protective strategies and advanced therapies for a number of cardiovascular-related diseases.
Current PhD Students:
Mr Ahmed Alasseri
Project Title: ERK5 Signalling in Angiogenesis
Zhou, L.; Lyons-Rimmer, J.; Ammoun, S.; Müller, J.; Lasonder, E.; Sharma, V.; Ercolano, E.; Hilton, D.; Taiwo, I.; Barczyk, M.; Hanemann, C.O. (2015) The Scaffold Protein KSR1, A Novel Therapeutic Target for the Treatment of Merlin-Deficient Tumors Oncogene, doi: 10.1038/onc.2015.404. [Epub ahead of print]
Hogg, E.L.; Müller, J.; Corrêa, S.A.L. (2015) “Does the MK2-Dependent Production of TNFα Regulate mGluR-Dependent Synaptic Plasticity?“ Current Neuropharmacology, doi: 10.2174/1570159X13666150624165939. [Epub ahead of print]
Eales, K.L.; Palygin, O.; O’Loughlin, T.; Rasooli-Nejad, S.; Gaestel, S.; Müller, J.; Collins, D.R.; Pankratov, Y; Corrêa, S.A.L. (2014) “The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility” Nature Communications 5:4701
Nithianandarajah-Jones, G.N.; Wilm, B.; Goldring, C.E.P.; Müller, J.; Cross, M.J. (2014) “The role of ERK5 in endothelial cell function” Biochemical Society Transactions 42, 1584-1589
Shaheen, F.; Müller, J.; Zammit, V.; Lehnert, H; Grammatopoulos, D. (2014) “Extra-nuclear Telomerase Reverse Transcriptase (TERT) Regulates Glucose Transport in Skeletal Muscle Cells” BBA - Molecular Basis of Disease 1842, 1762-1769
Nithianandarajah-Jones, G.N.; Wilm, B.; Goldring, C.E.; Müller, J.; Cross, M.J. (2012) “ERK5: structure, regulation and function” Cellular Signalling 24 (11), 2187-2196
Sarkar, D.; Shields, B.; Davies, M.L.; Müller, J.; Wakeman, J.A. (2012) “Brachyury confers cancer stem cell characteristics on colorectal cancer cells” International Journal of Cancer 130 (2), 328-337
Canal, F.; Palygin, O.; Pankratov, Y; Corrêa, S.A.L; Müller, J. (2011) “Compartmentalization of the MAPK scaffold protein KSR1 modulates synaptic plasticity in hippocampal neurons” FASEB Journal 25 (7), 2362-2372
Roberts, O.L.; Holmes, K; Müller, J.; Cross, D.A.L. Cross, M.J. (2010) “ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells” Journal of Cell Science 123, 3189-3200.
Price N.T.; Jackson, V.N.; Müller J.; Moffat, K.; Matthews, K.L.; Orton, T.; Zammit, V.A. (2010) “Alternative exon usage in the single CPT1 gene of Drosophila generates functional diversity in the kinetic properties of the enzyme: differential expression of alternatively spliced variants in Drosophila tissues” Journal of Biological Chemistry 285, 7857-7865
Corrêa, S.A.; Müller, J.; Collingridge, G.L.; Marrion, N.V. (2009) “Rapid endocytosis provides restricted somatic expression of a K+ channel in central neurons” Journal of Cell Science 122, 4186-4194
Roberts O.L., Holmes K., Müller J., Cross D.A., Cross M.J. (2009) “ERK5 and the regulation of endothelial cell function” Biochemical Society Transactions 37, 1254-1259
Dougherty M.K.*; Müller J.*; Ritt D.A.; Zhou M.; Zhou X.Z.; Copeland T.D.; Conrads T.P.; Veenstra T.D.; Lu K.P.; Morrison D.K. (2005) “Regulation of Raf-1 by Direct Feedback Phosphorylation” Molecular Cell 17, 215-224 *These authors contributed equally to this work
Müller, J.; Ritt, D.A.; Copeland, T.D.; Morrison, D.K. (2003) “Functional Analysis of C-TAK1 Substrate Binding and Identification of PKP2 as a New C-TAK1 Substrate” EMBO Journal 22, 4431-4442
Müller, J.; Morrison, D.K. (2002) “Assay of Raf-1 activity” Methods in Enzymology 345, 490-498
Müller, J.; Ory, S.; Copeland, T.; Piwnica-Worms, H.; Morrison, D.K. (2001) “C-TAK1 Regulates Ras Signalling by Phosphorylating the MAPK Scaffold, KSR1” Molecular Cell 8, 983-993
Müller, J.*; Cacace, A.M.*; Lyons, W.E.; McGill, C.B.; Morrison, D.K. (2000) “Identification of B-KSR1, a Novel Brain-Specific Isoform of KSR1 that Functions in Neuronal Signalling” Molecular and Cellular Biology, 20, 5529-5539 *These authors contributed equally to this work
Browser does not support script.