Matthew James Smith
Biologie du cancer, biologie structurale, signalisation cellulaire
Profile
Research expertise
La recherche menée par Matthew J. Smith et son équipe vise à intégrer des approches expérimentales modernes à la biologie structurelle, à la biophysique, à la bio-informatique évolutive ainsi qu’à la biologie cellulaire dans le but d’identifier et de comprendre une signalisation anormale de cancer tant au niveau systémique que mécanique. Plus précisément, ils exploreront la corrélation entre les mutations génétiques, la structure des protéines altérées et les réseaux de protéines perturbés, déclenchant la transformation des cellules et la dissémination métastasique.
THÈMES
- GTPases RAS
- Fonction des protéines
- Signalisation MAPK
- Voies des suppresseurs de tumeurs
- Cytosquelette des microtubules
- Réseaux de signalisation
- Spectroscopie RMN
- Cristallographie aux rayons X
- Cryo-EM
- Protéomique
INTÉRÊTS DE RECHERCHE
- Explorer les propriétés biophysiques des RAS GTPases
- Élucider la signalisation en aval des GTPases
- Caractériser le « protéome obscur » des partenaires peu étudiés des GTPases-effecteurs
- Examiner l'impact des mutations cancéreuses sur la signalisation proliférative
- Développer de nouvelles et meilleures technologies pour caractériser la fonction des protéines
Affiliations and responsabilities
Research affiliations
Teaching and supervision
Teaching
Courses taught (current session only)
Programs
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Complex interplay between RAS superfamily GTPases and tumour suppressor RASSF effectors
Cycle : Doctoral
Grade : Ph. D.
Using BioID to study RAS signaling to the Hippo pathway
Cycle : Master's
Grade : M. Sc.
RAS small GTPase signalling to the enigmatic RASSF death effectors
Cycle : Doctoral
Grade : Ph. D.
Projects
Research projects
Regulation of RAS driven cellular proliferation by SHOC2 and the MRAS GTPase
Development and preclinical validation of first-in-class dual inhibitors of the atypical MAP kinases ERK3 and ERK4
Regulation of cytokinesis by the novel and conserved flavin-dependent monooxygenase enzymes OSGN-1/OSGIN
Investigation into RAS GTPase control of cell adhesion and proliferation through alternative downstream effectors
Systematic mapping of the global ARF network interactome by BioID coupled to functional studies to reveal novel biological functions
RAS-MAPK signal transduction in normal and cancer cells
Canada Research Chair in Cancer Signalling and Structural Biology
Atomiclevel visualization of signalling protein activity in living mammalian cells using InCell NMR spectroscopy
Development and preclinical validation of first-in-class dual inhibitors of the atypical MAP kinases ERK3 and ERK4
Atomiclevel visualization of signalling protein activity in living mammalian cells using InCell NMR spectroscopy
Elucidation of the molecular mechanisms governing currently untargeted RAS effector pathways towards novel therapeutic approaches for the most refractory human cancers
Développement d'une série inédite d'inhibiteurs des GTPases RAS
Structure-function analysis of a novel KRAS effector complex and its role in metastasis
Développement d'une série inédite d'inhibiteurs des GTPases RAS
FI - Development of nanoscale device arrays to investigate the biophysical properties of fundamental cellular switch proteins
FD - Development of nanoscale device arrays to investigate the biophysical properties of fundamental cellular switch proteins
Développement d'une série inédite d'inhibiteurs des GTPases RAS
Développement d'une série inédite d'inhibiteurs des GTPases RAS
Canada Research Chair in Cancer Signalling an Structural Biology
Supplément COVID-19 CRSNG_Atomiclevel visualization of signalling protein activity in living mammalian cells using InCell NMR spectroscopy
Real-time surveillance of multiplexed, reversible cancer signalling markers in perturbed RAS networks.
Real-time surveillance of multiplexed, reversible cancer signalling markers in perturbed RAS networks.
Analyses structurales et systémiques des protéines modulatrices de la signalisation RAS oncogénique pour de nouvelles approches thérapeutiques contre les cancers humains
Analyses structurales et systémiques des protéines modulatrices de la signalisation RAS oncogénique pour de nouvelles approches thérapeutiques contre les cancers humains
Groupe de recherche axe sur la structure des proteines (GRASP)
Integrated structure/systems analyses of oncogenic RAS signaling towards novel therapeutic approaches for human cancers
Outreach
Publications and presentations
Publications
Bernal Astrain, G., R. Strakhova, CH. Jo, E. Teszner, R.C. Killoran, and M.J. Smith. The small GTPase MRAS is a broken switch. Nature Communications 2024; 16: 647.
Rambaud, B., M. Joseph, F-C. Tsai, C.D. Jamblinne, R. Strakhova, E. Del Guidice, R. Sabelli, M.J. Smith, P. Bassereau, D.R. Hipfner and S. Carréno. STRIPAK controls cell-cell communication by promoting cytoneme biogenesis through the membrane-sculpting function of Slik. EMBO Journal 2024; Accepted/In press.
Comtois-Marotte, S., E. Bonneil, C. Li, M.J. Smith, and P. Thibault. Epitope and paratope mapping of a SUMO-remnant antibody using cross-linking mass spectrometry and molecular docking. Journal of Proteome Research 2024; Accepted/In press.
Lacroix, L., E. Goupil, M.J. Smith, and J-C. Labbé. Leaving the mark: FMOs as an emerging class of cytokinetic regulators. Cell Cycle 2024; Accepted/In press.
Singh, S., G. Bernal Astrain, A.M. Hincapie, M. Goudreault and M.J. Smith. Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP. EMBO Reports 2024. 25: 3574-3600.
Quirion, L., A. Robert, J. Boulais, S. Huang, G. Bernal Astrain, R. Strakhova, CH. Jo, Y. Kherdjemil, D. Faubert, M-P Thibault, M. Kmita, J.M. Baskin, A-C Gingras, M.J. Smith, and J-F Côté. ARF-family global interactome mapping uncovers spatial organization of cellular signaling pathways. Journal of Cell Science 2024; 137 (9): jcs262140.
Strakhova, R. and M.J. Smith. Profiling complex RAS-effector interactions using NMR spectroscopy. Editors: Stephen, A.G. and D. Esposito. In: Methods in Molecular Biology; KRAS: Methods and Protocols. United States: Springer 2024; 2797: 195-209.
Smith M.J. Defining bone fide effectors of RAS GTPases. BioEssays 2023; 45 (9): e2300088.
Elkholi I.E., J. Boulais, M.-P. Thibault, H.-D. Phan, A. Robert, L.B. Lai, D. Faubert, M.J. Smith, V. Gopalan, and J.-F. Côté. Mapping the MOB proteins’ proximity network reveals a unique interaction between human MOB3C and the RNase P complex. Journal of Biological Chemistry 2023; 299 (9): 105123.
Tran, V., I. Desanlis, R.C. Killoran, K.S. Ravichandran, M.J. Smith, M. Kmita and JF Côté. Manipulating the conformational state of Elmo2 reveals that myoblast fusion can be exploited for regenerative therapy in muscular fusiopathies. Nature Communications 2022; 13 (1): 7077.
Goudreault, M., V. Gagné, C.H. Jo, S. Singh, R.C. Killoran, A.C. Gingras and M.J. Smith. Afadin couples RAS GTPases to the polarity rheostat Scribble. Nature Communications 2022; 13 (1): 4562.
Bernal Astrain, G., M. Nikolova and M.J. Smith. Functional diversity in the RAS subfamily of small GTPases. Biochemical Society Transactions 2022; 50 (2): 921-33.
Killoran, R.C. and M.J. Smith. NMR detection methods for profiling RAS nucleotide cycling. Editors: Rubio, I. and I. Prior. In: Ras Activity and Signaling: Methods and Protocols. United States: Springer 2021; 2262: 169-182.
Singh, S. and M.J. Smith. RAS GTPase signalling to alternative effector pathways. Biochemical Society Transactions 2020; 48(5): 2241–2252.
Dhanaraman T., S. Singh, R.C. Killoran, A. Singh, X. Xu, J. Shifman, and M.J. Smith. RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway. Science Signaling 2020; 13(653): 1-15.
Chang, L., J. Yang, C.H. Jo, Z. Zhang, A. Boland, S.H. McLaughlin, A. Abu-Thuraia, R.C. Killoran, M.J. Smith*, J-F. Côté* and D. Barford. Insights into regulation of the DOCK−ELMO−RAC signaling module from structures of DOCK2−ELMO1 and its complexes with RAC and RHOG. Nature Communications 2020; 11(1): 3464. *equal contributions
Killoran R.C. and M.J. Smith. Conformational resolution of nucleotide cycling and effector interactions for multiple small GTPases determined in parallel. Journal of Biological Chemistry 2019; 294, 9937-9948.
Smith M.J.*, E. Ottoni, N. Ishiyama, M. Goudreault, A. Haman, C. Meyer, M. Tucholska, G. Gasmi-Seabrook, S. Menezes, R.C. Laister, M.D. Minden, R. Marschalek, A.-C. Gingras, T. Hoang and M. Ikura*. Evolution of AF6-RAS Association and Implications in Mixed-Lineage Nature Communications 2017; 8(1): 1099. *co-corresponding authors
Spencer-Smith R., A. Koide, Y. Zhou, R. Eguchi, F. Sha, P. Gajwani, D. Santana, A. Gupta, M. Jacobs, E. Herrero-Garcia, J. Cobbert, H. Lavoie, M.J. Smith, T. Rajakulendran, E. Dowdell, M. Nazir Okur, I. Dementieva, F. Sicheri, M. Therrien, J.F. Hancock, M. Ikura, S. Koide, J.P. O’Bryan. Inhibition of Ras function through targeting an allosteric regulatory site. Nature Chemical Biology 2017; 13: 62-68.
Fang Z., C.B. Marshall, J.C. Yin, M.T. Mazhab-Jafari, G.M. Gasmi-Seabrook, M.J. Smith, T. Nishikawa, Y. Xu, B.G. Neel, and M. Ikura. Biochemical Classification of Disease-Associated Mutants of RAS-Like Protein Expressed in Many Tissues (RIT1). Journal of Biological Chemistry 2016; 291(30): 15641-52.
Park S., N.R. Bin, M. Michael Rajah, B. Kim, T.C. Chou, S.A. Kang, K. Sugita, L. Parsaud, M. Smith, P.P. Monnier, M. Ikura, M. Zhen, and S. Sugita. Conformational states of syntaxin-1 govern the necessity of N-peptide binding in exocytosis of PC12 cells and Caenorhabditis elegans. Molecular Biology of the Cell 2016; 27(4): 669-685.
Mazhab-Jafari M.T., C.B. Marshall, M.J. Smith, G.M.C. Gasmi-Seabrook, P.B. Stathopoulos, F. Inagaki, L.E. Kay, B.G. Neel and M. Ikura. Oncogenic and RASopathy-associated KRAS mutations relieve membrane-dependent occlusion of the effector-binding site. Proceedings of the National Academy of Sciences U S A 2015; 112 (21): 6625-30.
Smith M.J., C.B. Marshall, F. Theillet, A. Binolfi, P. Selenko and M. Ikura. Real-time NMR monitoring of biological activities in complex physiological environments. Current Opinion in Structural Biology 2015; 32:39–47.
Disciplines
- Cell Biology
- Biochemistry
Areas of expertise
- Cell Signaling and Cancer
- Mutation (Process)
- Enzymes and Proteins
- Proteins
- Host-Tumour Interaction
- Growth Factors (Cancer)
- Cell Therapy of Cancer