Michael Lund Nielsen

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An emerging concept of modern biology relates to the systematic understanding of cellular networks co-regulated via post-translational modifications (PTMs). The research focus of the Nielsen group is to develop novel proteomics methods and technologies for studying underexplored PTMs on a systems-level approach. Such developments allows the Nielsen group to elucidate hitherto uncharacterized PTMs and provide a better understanding of their biological implications in human cells, while uncovering the functional impact they exert in cellular phenotypes and diseases. Key achievement in this field is the development of proteomic strategies for analysis of endogenous SUMOylation, arginine methylation and ADP-ribosylation in a systems-wide manner. These methods has allowed the Nielsen group to investigate these emerging PTMs at an endogenous level, thus positions the group with unique analytical capabilities for studying the modifications in a range of cellular and biological conditions. Most recently, the Nielsen group has focused on exploring the cellular extent of ADP-ribosylation catalyzed via the nuclear ADP-ribosyltransferase PARP1. As PARP1 is associated with the occurrence and progression of various diseases, PARP inhibitors aimed at interfering with ADP-ribosylation catalyzed by PARP1 are commonly used for medical interventions. While the enzymatic function and cellular implications of PARP inhibitors remains elusive, the Nielsen group now utilizes its leading technology to pinpoint the protein targets of PARP1. Following this, the group established that serine residues are the preferred acceptor site of PARP1 on a proteome-wide scale, exemplifying the analytical advantages of generating powerful data resources for elucidation of uncharacterized PTMs using high-resolution mass spectrometry.

Selected publications

1. Published

   Site-specific characterization of endogenous SUMOylation across species and organs

   Hendriks, Ivo Alexander, Lyon, D., Su, D., Skotte, Niels Henning, Daniel, J. A., Jensen, Lars Juhl & Nielsen, Michael Lund, 2018, In: Nature Communications. 9, p. 1-17 2456.

   Research output: Contribution to journal › Journal article › Research › peer-review

2. Published

   Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism

   Skotte, Niels Henning, Andersen, Jens Velde, Santos, A., Aldana, Blanca I., Willert, C. W., Nørremølle, Anne, Waagepetersen, Helle S. & Nielsen, Michael Lund, 2018, In: Cell Reports. 23, 7, p. 2211-2224 14 p.

   Research output: Contribution to journal › Journal article › Research › peer-review

3. Published

   Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation

   Buch-Larsen, Sara Charlotte, Hendriks, Ivo Alexander, Lyon, D., Jensen, Lars Juhl & Nielsen, Michael Lund, 2018, In: Cell Reports. 24, 9, p. 2493-2505

   Research output: Contribution to journal › Journal article › Research › peer-review

4. Published

   Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation

   Hendriks, Ivo Alexander, Lyon, D., Young, C., Jensen, Lars Juhl, Vertegaal, A. C. O. & Nielsen, Michael Lund, Mar 2017, In: Nature Structural and Molecular Biology. 24, 3, p. 325-336 12 p.

   Research output: Contribution to journal › Journal article › Research › peer-review

5. Published

   Proteome-Wide Identification of In Vivo ADP-Ribose Acceptor Sites by Liquid Chromatography-Tandem Mass Spectrometry

   Buch-Larsen, Sara Charlotte, Leutert, M., Bilan, V., Martello, R., Jungmichel, S., Young, C., Hottiger, M. O. & Nielsen, Michael Lund, 2017, Poly(ADP-Ribose) Polymerase. Tulin, A. V. (ed.). Humana Press, Vol. 1608. p. 149-162 14 p. (Methods in molecular biology (Clifton, N.J.)).

   Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review

6. Published

   Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

   Buch-Larsen, Sara Charlotte, Sylvestersen, K. B., Mund, Andreas, Lyon, D., Mullari, M., Madsen, M. V., Daniel, J. A., Jensen, Lars Juhl & Nielsen, Michael Lund, 30 Aug 2016, In: Science Signaling. 9, 443, 14 p., rs9.

   Research output: Contribution to journal › Journal article › Research › peer-review

7. Published

   Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue

   Martello, R., Leutert, M., Jungmichel, S., Bilan, V., Buch-Larsen, Sara Charlotte, Young, C., Hottiger, M. O. & Nielsen, Michael Lund, 1 Oct 2016, In: Nature Communications. 7, 13 p., 12917.

   Research output: Contribution to journal › Journal article › Research › peer-review

8. Published

   Specificity and commonality of the phosphoinositide-binding proteome analyzed by quantitative mass spectrometry

   Jungmichel, S., Sylvestersen, K. B., Choudhary, Chunaram, Nguyen, S., Mann, Matthias & Nielsen, Michael Lund, 13 Feb 2014, In: Cell Reports. 6, 3, p. 578-91 14 p.

   Research output: Contribution to journal › Journal article › Research › peer-review

9. Published

   Proteome-wide Identification of Poly(ADP-Ribosyl)ation Targets in Different Genotoxic Stress Responses

   Jungmichel, S., Rosenthal, F., Altmeyer, M., Lukas, Jiri, Hottiger, M. O. & Nielsen, Michael Lund, 24 Oct 2013, In: Molecular Cell. 52, 2, p. 272-285 14 p.

   Research output: Contribution to journal › Journal article › Research › peer-review