Clausen Group – University of Copenhagen

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Department of Cellular and Molecular Medicine > Research Groups > Clausen Group

Clausen Group

Glycomics Program
Copenhagen Center for Glycomics 
Copenhagen Consortium for Designer Organisms

Research Interests

The overarching goals for Copenhagen Center for Glycomics (CCG) are to identify diseases caused by defects in glycosylation and to uncover novel functions of glycosylation. Technical barriers have left the glycomics field under-explored with a huge potential for discovery and biomedical applications. We are developing novel enabling technologies to overcome these barriers using a genetic approach to glycomics. Our unique strategies to glycomics are based on a genetic entry point and designed for open-ended and opportunistic Ome-wide discovery. The grand idea is to transform glycosciences from a field largely only approachable to specialists into a mainstream “Omics” field approachable to non-specialists with an ease comparable to the genome and proteome fields today. Our specific discovery programs GlycoDisplay, GlycoCRISPR, GlycoDesign, and GlycoView are developing unique reagents, tools and community resources that will help bring glycosciences into a new phase where studying the biology of glycans becomes as intuitive as building with “Lego”.

Current Project Areas

Lundbeck Foundation funded program (2017-19) to develop an innovative cell-based platform to display all human glycans individually in an arrayable format. Such a library of genetically engineered cells with different glycans will enable high throughput screening and discovery of glycan functions in the natural context of the cell. The glycan cell library is sustainable and addressable by any multiplex assay format.

Collaborators

Ramon Hurtado-Guerrero, Zaragoza
Adam Linstedt, Pittsburg
Leonor David, Porto
Hans Schreiber, Chicago
Carl June, Philadelphia
Dan Rader, Philadelphia
Sabine Strahl, Heidelberg
Eduardo Osinaga, Montevideo
Ulla Petäjä-Repo, Oulu
Lawrence Shapiro, New York

Selected publications

  • Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB, Schjoldager KTG, Lavrsen K, Dabelsteen S, Pedersen NB, Marcos-Silva L, Gupta R, Bennett EP, Mandel U, Wandall H, Brunak S, Levery SB, Clausen H (2013) Precision Mapping of the Human GalNAc-Type O-Glycoproteome – First Generation View From 12 Human SimpleCells. EMBO J 32(10):1478-88

  • Vester-Christensen MB, Halim A, Joshi HJ, Steentoft C, Bennett EP, Levery SB, Vakhrushev SY, Clausen H (2013) Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins. Proc Natl Acad Sci USA 110(52):21018-23

  • Steentoft C, Bennett EP, Schjoldager KT, Vakhrushev SY, Wandall HH, Clausen H. (2014) Precision genome editing - a small revolution for glycobiology. Glycobiology 24(8):663-80

  • Yang Z, Wang S, Halim A, Schulz MA, Frodin M, Rahman SH, Vester-Christensen MB, Behrens C, Kristensen C, Vakhrushev SY, Bennett EP, Wandall HH, Clausen H. (2015) Engineered CHO cells for production of diverse, homogeneous glycoproteins. Nat Biotechnol 33(8):842-4

  • Goth CK, Halim A, Khetarpal SA, Rader DJ, Clausen H, Schjoldager KT. (2015) A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation. Proc Natl Acad Sci USA 112(47):14623-8

  • Halim A, Larsen IS, Neubert P, Joshi HJ, Petersen BL, Vakhrushev SY, Strahl S, Clausen H. (2015) Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast. Proc Natl Acad Sci USA 112(51):15648-53

  • Posey AD, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone J, Madsen TD, Schreiber K, Haines KM, Cogdill AP, Chen TJ, Song D, Scholler J, Krantz DM, Feldman MD, Young R, Keith B, Schreiber H, Clausen H, Johnson LA, June CH (2016) Engineering T Cells to Target Abnormal Self-Antigens. Immunity 44(6):1444-54.

  • Khetarpal SA, Schjoldager KTG, Christoffersen C, Raghavan A, Edmondson AC, Reutter HM, Ahmed B, Ouzzani R, Peloso GM, Vitali C, Zhao W, Varshini A, Millar JS, Park Y, Fernando G, Livanov V, Choi S, Noé E, Patel P, Ho S, Global Lipids Genetics Consortium, Kirchgessner TG, Wandall HH, Hansen L, Bennett EP, Vakrushev SY, Saleheen D, Kathiresan S, Brown CD, Jamra AB, LeGuern E, Clausen H, Rader DJ. (2016) Loss of function of GALNT2 lowers high density lipoproteins in humans, nonhuman primates, and rodents. Cell Metabolism 24(2):234-45.

  • Larsen ISB, Narimatsu Y, Joshi HJ, Yang Z, Harrison OJ, Brasch J, Shapiro L, Honig B, Vakhrushev SY, Clausen H, Halim A. (2017) Mammalian O-mannosylation of Cadherins and Plexins is Independent of Protein O-mannosyltransferase 1 and 2. J Biol Chem 292(27):11586-11598

  • Larsen ISB, Narimatsu Y, Joshi HJ, Siustaite L, Harrison OJ, Brasch J, Goodman K, Hansen L, Shapiro L, Honig B, Vakhrushev SY, Clausen H, Halim A. (2017) Discovery of a novel O-mannosylation pathway selectively serving cadherins and protocadherins. Proc Natl Acad Sci USA 114(42):11163-11168