Michael Sacher, PhD

Education

PhD (McGill University)

Research interests

A eukaryotic cell is composed of many different compartments (eg. nucleus, mitochondria, Golgi apparatus, vacuole, endoplasmic reticulum). Each of these organelles is surrounded by a membrane, thus separating the inside of the organelle from the cytoplasm. Furthermore, each compartment contains its own unique protein and lipid composition. Material can be transferred between specific organelles by small vesicles that bud from one compartment and fuse with another compartment. Faulty sorting of this material leads to numerous human diorders and is a fundamental process in cell biology. The main question in our research is: how is the specificity in vesicle targeting ensured? We focus on a protein complex called TRAPP and are actively studying the functions of the components of this complex, several of which have been implicated in human disorders. Therefore, our work involves model systems as well as cells derived from patients with TRAPP subunit mutations.

Funding sources

CIHR, NSERC, Concordia University, TANGO2 Research Foundation

Awards and media

TANGO2 Foundation podcast (2021)

JIMD podcast on TANGO2 paper (2020)

CIHR New Investigator Award (2007-2012)

Maud Menten New Principal Investigator Prize (Biomedicine) 2007 (CIHR Institute of Genetics)

Dean's New Scholar Award (Article and introduction)

Arts and Science fetes Medical Researchers

Concordia Journal article: Decoding Cell Transport System.

Cell Biology (Biol 266), Fall 2020, We/Fr section
Advanced Laboratory in Molecular Biology (Biol 466/689), Winter 2021

Stanga,D.,Zhao,Q., Milev,M.P., Saint-Dic,D., Mallebreara,C.J. and Sacher,M. (2019) TRAPPC11 functionsin autophagy through recruitment of ATG2B-WIPI4/WDR45 to preautophagosomalmembranes. Traffic 20, 325-345

Sacher,M.,Shahrzad,N., Kamel,H and Milev,M. (2019) TRAPPopathies, an emerging set of disorderslinked to variants in the genes encoding transport protein particle(TRAPP)-associated proteins Traffic 20,5-26

Milev,M.P.,Graziano,C.,  Karall,D., Kuper,W.F.E.,Al-Deri,N., Cordelli,D.M., Haack,T.B., Danhauser,K., Iuso,A., Palombo,F., Pippucci,T., Prokisch,H.,Saint-Dic,D., Seri,M., Stanga,D., Cenacchi,G., van Gassen,K.L.I., Zschocke,J.,Fauth,C., Mayr,J.A., Sacher,M. and van Hasselt,P.M. Bi-allelic mutations in TRAPPC2L result in a neurodevelopmentaldisorder of varying severity and have an impact on Rab11 in fibroblasts. J. Med. Genet. 55, 753-764Larson,A.A., Baker II,P.R., Milev,M.P., Press,C.A.,Sokol,R.J., Cox,M.O., Lekostaj,J.K., Stence,A.A., Bossler,A.D., Mueller,J.M.,Prematilake,K., Tadjo,T.F., Williams,C.A., Sacher,M. and Moore,S.A. (2018) TRAPPC11 and GOSR2 mutationsassociate with hypoglycosylation of α-dystroglycan and muscular dystrophy. SkeletalMuscle 8,17

Milev,M.P., Grout,M.E., Saint-Dic,D., Cheng,Y.-H.H.Glass,I.A., Hale,C.J., Hanna,D.S., Dorschner,M.O., Prematilake,K., Shaag,A.,Elpeleg,O., Sacher,M.,Doherty,D. and Edvardson,S. (2017) Mutations in TRAPPC12 manifestby progressive childhood encephalopathy and Golgi dysfunction. Am. J.Hum. Genet.101, 291-299

Koehler,K., Milev,M., Prematilake,K., Reschke,F.,Kutzner,S., Landgraf,D., Utine,E., Hazan,F., Diniz,G.,Schuelke,M., Huebner,A. and Sacher,M. (2017) Anovel TRAPPC11mutation in two Turkish families with cerebralatrophy, global retardation, therapy refractory seizures, achalasia andalacrimia J. Med. Genet.54,176-185

DeRossi,C.,  Vacaru,A., Rafiq,A., Cinaroglu,A.,Imrie,D., Nayar,S., Milev,M.P., Stanga,D., Kadakia,D.,Gao,N.,  Chu,J., Freeze,H., Lehrman,M., Sacher,M. and Sadler,K.C. (2016) trappc11 isrequired for protein glycosylation in zebrafish and humans Mol. Biol.Cell 27, 1220-1234

Liang, W.C., Zhu, W.,Mitsuhashi, S., Noguchi, S., Sacher, M.,Ogawa, M., Shih,H.H., Jong, Y.J. and Nishino, I. (2015) Congenital musculardystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations:broadening of the phenotype. Skeletal Muscle 5,29

Milev,M., Hasaj,B., Saint-Dic,D.,Snounou,S., Zhao,Q. andSacher,M. (2015) TRAMM/TrappC12 plays a role inchromosome congression,kinetochore stability and CENP-E recruitment J. Cell Biol. 209,221-234

Brunet,S. and Sacher,M. (2014) In sickness and in health:The role of TRAPP and associated proteins in disease. Traffic 15,803-818

Bögershausen,N.,Shahrzad,N.,Chong,J.X.,  vonKleist-Retzow,J.-C., Stanga,D., Li,Y., Bernier,F.P., Loucks,C.M.,Wirth,R., Puffenberger,E.G.,Hegele,R.,Schreml,J., Lapointe,G.,Keupp,K., Brett,C.L.,Anderson,R., Hahn,A.,Innes,A.M.,Suchowersky,O., Mets,M.B., Nürnberg,G.,McLeod,D.R.,Thiele,H.,Waggoner,D., Altmüller,J.,Boycott,K.M., Schoser,B.,Nürnberg,P.,Ober,C., Heller,R., Parboosingh,J.S.,Wollnik,B., Sacher,M. andLamont,R.E.(2013) Recessive TRAPPC11 mutations cause a disease spectrum of limbgirdlemuscular dystrophy and myopathy with movement disorder andintellectualdisability. Am. J. Hum. Genet. 93, 181-190

Brunet,S., Shahrzad,N., St.-Dic,D.,Dutczak,H. andSacher,M. (2013) A trs20mutation in Saccharomycescerevisiaethat mimics an SEDT-causing mutation destabilizes TRAPP III andblocks both selectiveand non-selective autophagy: a model for TRAPP IIIorganization. Traffic 19, 1091-1104

Scrivens,P.J., Shahrzad,N., Moores,A., Morin,A.,Brunet,S. and Sacher,M. (2009) TRAPPC2L is a novel, highly conservedTRAPP-interacting protein Traffic, 10, 724-736

Sacher,M., Kim,Y.-G., Lavie,A., Oh,B.-H. andSegev,N. (2008) The TRAPP complex: insights into its architecture and functionTraffic, 9, 2032-2042

Kim,Y.-G., Raunser,S., Munger,C., Wagner,J.,Song,Y.-L., Cygler,M., Walz,T., Oh,B.-H. and Sacher,M. (2006) The architectureof the multisubunit TRAPP I complex suggests a model for vesicle tethering Cell127, 817-830

Kim, Y.-G., Sohn ,E.J., Seo, J., Lee, K.-J.,Lee, H.-S., Hwang, I., Whiteway, M., Sacher, M. and Oh, B.-H. (2005) Crystalstructure of bet3 reveals a novel mechanism for Golgi localization of tetheringfactor TRAPP. Nature Struct. Mol. Biol. 12, 38-45



Sacher, M., Barrowman, J., Wang, W., Horecka,J., Zhang, Y., Pypaert ,M. and Ferro-Novick, S. (2001) TRAPP I implicated in thespecificity of tethering in ER-to-Golgi transport. Mol. Cell, 7, 433-442



Barrowman, J., Sacher, M. and Ferro-Novick, S. (2000) TRAPP stably associates with the Golgi and is required for vesicledocking. EMBO J. 19, 862-869



Sacher, M., Jiang, Y., Barrowman, J., Scarpa,A., Burston, J., Zhang, L., Schieltz, D., Yates III, J.R., Abeliovich, H. andFerro-Novick, S. (1998) TRAPP, a highly conserved novel complex on the cis-Golgithat mediates vesicle docking and fusion. EMBO J. 17, 2494-2503