Research output per year
Research output per year
Blegdamsvej 3, 2200 København N.
Blegdamsvej 3
2200 København N.
Research activity per year
Glycosylation is an essential cellular process that involves the covalent attachment of glycans (carbohydrates/sugars) to proteins; glycans play important roles in maintaining normal cellular functions and dysregulation of processes related to protein glycosylations are known to cause various diseases, e.g. cancer and developmental disorders. Our group is interested in the biosynthesis, regulation and biochemistry of O-linked glycosylations with a special focus on protein O-mannosylations (see our OA article in Cell). We use a combination of methods, including advanced mass spectrometry, to study structures, map site-specific locations and quantify changes of protein O-mannosylations on a proteome-wide scale. In addition, we use CRISPR/Cas9 gene editing for KO/KI of glycogenes in our efforts to study and understand enzymatic pathways involved in protein O-mannosylation.
O-mannosylation was for a long time believed to be a rare type of protein modification in mammals. Until recently, α-dystroglycan (αDG), a component of the dystrophin complex, remained the only well-characterized protein with respect to O-mannosylation sites and structures. Building on the SimpleCell technology developed at Copenhagen Center for Glycomics (CCG), we established a glycoproteomic workflow for studying protein O-mannosylations on a proteome-wide scale. This approach allowed us to greatly expand the human O-mannose glycoproteome and led to the discovery of cadherins and protocadherins as major carriers of O-mannosylations. Using the SimpleCell technology, we recently uncovered that O-mannosylation of the cadherin superfamily is not mediated by the classical POMT1/POMT2 enzymes and identified the glycosyltransferase family (GT105), composed of TMTC1-4, that initiates the cadherin-specific O-mannosylation. Currently, we are characterizing the TMTC1-4 enzyme family, exploring the substrate specificities/interactomes of individual TMTC family members and studying the disease-causing mutations in this enzyme family. Our ambitions are to gain further understanding on cellular processes related to the function of cadherin-specific O-mannosylation in health and disease (e.g. Cobblestone lissencephaly).
In addition to the cadherin superfamily, we have identified plexins as a major class of cell-surface O-mannosylated proteins. The IPT/TIG domains of plexins are frequently O-mannosylated on specific β-strands but, intriguingly, this O-mannosylation doesn’t seem to be mediated by POMT1/POMT2 or the TMTC1-4 family. Our results thus indicate that other, as yet unknown glycosyltransferases are present in mammalian systems and are responsible for directing O-mannosylation specifically to proteins with IPT/TIG folds. Using the SimpleCell platform, we are currently screening candidate genes to test this hypothesis and to identify the novel glycosyltransferase enzymes responsible for O-mannosylation in mammalian cells.
CV Adnan Halim, Jan 2020
Adnan Halim, Ph.D.
[email protected]
Nationality: Swedish,
ORCID: 0000-0003-1629-187X
URL: https://icmm.ku.dk/english/research-groups/halim-group/
Education
2008-2012: PhD (Medical Science), Dept. of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Supervisor: Göran Larson
2002-2007: MSc (Chemistry), University of Gothenburg
Academic appointments
2016- Research Associate Professor, Copenhagen Center for Glycomics, University of Copenhagen
2016-2018: Visiting Research Associate Professor, Marie Curie fellow, Rockefeller University, USA
2014-2016: Assistant Professor, Copenhagen Center for Glycomics, University of Copenhagen
2012-2014: Postdoc, Copenhagen Center for Glycomics, University of Copenhagen
Grants
2019: Villum Fonden – Villum Young Investigator, Financial share: DKK 10,000,000; Role: PI
2019: Nordea Fonden – housing grant (6 months) for visiting prof. Vladislav Panin, Texas A&M University, Role: Co-applicant
2016: European Commission – Marie Skłodowska-Curie Individual Fellowship, Financial share: EUR 278,227; Role Co-PI
2016: The Novo Nordisk Foundation - Financial share: DKK 2,300,000; Role: PI
Bibliometric summary/citation information
Publications: 37 original papers and 5 reviews. (2x Cell, 1x Nature Biotechnol, 1x Nature Meth, 5x PNAS).
24 publications independent of PhD supervisor. 10 first-author; 4 corresponding.
Impact: H-index: 24; total citations >1800 (Google Scholar)
Academic Awards
2013: Honorary Phabian Award, Swedish Pharmaceutical Society
2012: Best thesis award, Institute of Biomedicine, University of Gothenburg
Patents and provisional applications
8916387 B2, Diagnosis and treatment of Alzheimer's disease, US patent
WO2016091268 A2, N-glycosylation, US provisional application
WO2017008982 A1, Production of N-glycoproteins for enzyme assisted glycomodification, US provisional application
US20170218032 A1, Yeast O-Mannose Nucleocytoplasmic glycosylation, US provisional application
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review
Research output: Contribution to journal › Review › Research › peer-review
Research output: Contribution to journal › Journal article › Research › peer-review