个人简介

B.Sc. in Biochemistry, McGill University Ph.D. in Biochemistry, UBC

研究领域

Cytoskeleton and sensory cilia in health and disease

The focus of our studies is to identify and characterise proteins found within the cilium, an evolutionarily ancient microtubule-based organelle found on virtually all human cells. Using the nematode C. elegans, we study intraflagellar transport, a kinesin- and dynein-dependent transport process necessary to forma and maintain the complex ciliary structure. We also aim to understand the makeup and function of the transition zone, a ‘gate’ that controls ciliary composition and thus function. Importantly, our biomedical research probes the molecular basis of several human disorders arising from ciliary dysfunction, including Bardet-Biedl Syndrome and Meckel syndrome. Such ‘ciliopathies’ are characterised by a wide range of ailments, such as obesity, kidney and heart anomalies, blindness, skeletal malformations, and neurosensory impairment.

近期论文

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Jensen VL, Carter S, Sanders AA, Li C, Kennedy J, Timbers TA, Cai J, Scheidel N, Kennedy BN, Morin RD, Leroux MR* and Blacque OE* (2016) Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport. PLoS Genet. 12, e1006469 abstract *co-corresponding authors Timbers TA, Garland SJ, Mohan S, Flibotte S, Edgley M, Muncaster Q, Au V, Li-Leger E, Rosell FI, Cai J, Rademakers S, Jansen G, Moerman DG and Leroux MR (2016) Accelerating Gene Discovery by Phenotyping Whole-Genome Sequenced Multi-mutation Strains and Using the Sequence Kernel Association Test (SKAT) PLoS Genet. 12, e1006235 abstract Loucks CM, Bialas NJ, Dekkers MP, Walker DS, Grundy LJ, Li C, Inglis PN, Kida K, Schafer WR, Blacque OE, Jansen G, and Leroux MR (2016) PACRG, a Protein Linked to Ciliary Motility, Mediates Cellular Signaling. Mol Biol Cell. 27, 2133-2144 abstract Li C, Jensen VL, Park K, Kennedy J, Garcia-Gonzalo FR, Romani M, De Mori R, Bruel AL, Gaillard D, Doray B, Lopez E, Rivière JB, Faivre L, Thauvin-Robinet C, Reiter JF, Blacque OE, Valente EM and Leroux MR (2016) MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone. PLoS Biol. 14, e1002416. abstract Avidor-Reiss T and Leroux MR (2015) Shared and Distinct Mechanisms of Compartmentalized and Cytosolic Ciliogenesis. Curr. Biol. 25, R1143-50. abstract Yee LE, Garcia-Gonzalo FR, Bowie RV, Li C, Kennedy JK, Ashrafi K, Blacque OE, Leroux MR and Reiter JF (2015) Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling. PLoS Genet. 11, e1005627. abstract Jensen VL, Li C, Bowie RV, Clarke L, Mohan S, Blacque OE and Leroux MR (2015) Formation of the transition zone by Mks5/Rpgrip1L establishes a ciliary zone of exclusion (CIZE) that compartmentalises ciliary signalling proteins and controls PIP2 ciliary abundance. EMBO J. 34, 2537-56. abstract Roberson EC, Dowdle WE, Ozanturk A, Garcia-Gonzalo FR, Li C, Halbritter J, Elkhartoufi N, Porath JD, Cope H, Ashley-Koch A, Gregory S, Thomas S, Sayer JA, Saunier S, Otto EA, Katsanis N, Davis EE, Attié-Bitach T, Hildebrandt F, Leroux MR and Reiter JF (2015) TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone. J. Cell Biol. 209, 129-142. abstract Nguyen PA, Liou W, Hall DH and Leroux MR (2014) Ciliopathy proteins establish a bipartite signaling compartment in a C. elegans thermosensory neuron. J. Cell Sci. 127, 5317-30. abstract Sung CH and Leroux MR (2013) The roles of evolutionarily conserved functional modules in cilia-related trafficking. Nat. Cell Biol. 15, 1387-97. abstract Mohan S, Timbers TA, Kennedy J, Blacque OE and Leroux MR (2013) Striated rootlet and non-filamentous forms of rootletin maintain ciliary function. Curr. Biol. 23, 2016-22. abstract Reviewed by Faculty of 1000! F1000 link Frédéric MY,* Lundin VF*,Whiteside MD, Cueva JG, Tu DK, Kang SYC, Singh H, Baillie DL, Hutter H, Goodman MB, Brinkman FSL and Leroux MR (2013) Identification of 526 Conserved Metazoan Genetic Innovations Exposes a New Role for Cofactor E-like in Neuronal Microtubule Homeostasis. PLoS Genet. 9, e1003804. abstract Sörgjerd KM, Zako T, Sakono M, Stirling PC, Leroux MR, Saito T, Nilsson P, Sekimoto M, Saido TC, and Maeda M (2013) Human Prefoldin Inhibits Amyloid-β (Aβ) Fibrillation and Contributes to Formation of Nontoxic Aβ Aggregates. Biochemistry 52, 3532-42 abstract Heydet D, Chen LX, Larter CZ, Inglis C, Silverman MA, Farrell GC and Leroux MR (2013) A truncating mutation of Alms1 reduces the number of hypothalamic neuronal cilia in obese mice. Dev. Neurobiol. 73, 1-13. abstract Reiter JF, Blacque OE, and Leroux MR (2012) The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep. 13, 608-18. abstract Warburton-Pitt SR, Jauregui AR, Li C, Wang J, Leroux MR and Barr MM (2012) Ciliogenesis in Caenorhabditis elegans requires genetic interactions between ciliary middle segment localized NPHP-2 (inversin) and transition zone-associated proteins. J. Cell Sci. 125, 2592-603. abstract Huang L*, Szymanska K* Jensen VL*, Janecke AR, Innes M, Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, Greenberg CR, McLeod R, Bernier FP, Chudley AE, Muller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, Bell SM, Adkins J, Zuniga FI, Ross KD, Wang J, Ban MR, Becker C, Nurnberg P, Douglas S, Craft CM, Akimenko M-A, Hegele RA, Ober C, Utermann G, Bolz HJ, Bulman DE, Katsanis N, Blacque OE, Doherty D, Parboosingh JS, Leroux MR^, Johnson CA, and Boycott KM (2011) TMEM237 Is Mutated in Individuals with a Joubert Syndrome Related Disorder and Expands the Role of the TMEM Family at the Ciliary Transition Zone. Am. J. Hum. Genet. 89, 713–30. *equal contribution ^co-corresponding authors abstract Mok CA, Healey MP, Shekhar T, Leroux MR, Héon E, Zhen M (2011) Mutations in a Guanylate Cyclase GCY-35/GCY-36 Modify Bardet-Biedl Syndrome-Associated Phenotypes in Caenorhabditis elegans. PLoS Genet. 7, e1002335. abstract Phirke P, Efimenko E, Mohan S, Burghoorn J, Crona F, Bakhoum MW, Trieb M, Schuske K, Jorgensen EM, Piasecki BP, Leroux MR and Swoboda P (2011) Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport. Dev. Biol. 357, 235-47. abstract Williams CL, Li C, Kida K, Inglis PN, Mohan S, Semenec L, Bialas NJ, Stupay RM, Chen N, Blacque OE, Yoder BK and Leroux MR (2011) MKS and NPHP modules cooperate to establish basal body/transition zone-membrane associations and ciliary gate function during ciliogenesis. J. Cell. Biol. 192, 1023-41. abstract