Prof. Michael Hottiger, Department of Molecular Mechanisms of Disease, University of Zürich, Zürich, Switzerland:

Host: Arto Pulliainen

The Hottiger-laboratory studies molecular regulatory mechanisms of inflammation, with special focus on the role of post-translation modifications in inflammatory signaling. They have contributed to the identification of protein ADP-ribosylation as a crucial process in the cellular response to detrimental stimuli, be it through genotoxicity, oxidative or metabolic stress, or excessive inflammation. Their current work focuses on the following questions: (i) Are ADP-ribosylation patterns cell-type specific or stimulus-specific, i.e. are there specific patterns that are associated with specific cell-physiological conditions? (ii) What are the modifiers (writer, binders, erasers) involved in those patterns? How can we specifically interfere with their activity to modulate the patterns? (iii) What are the regulatory mechanisms in ADP-ribosylation? How is the type and quantity of ADP-ribosylation patterns regulated? (iv) What are the downstream events of ADP-ribosylation, i.e. how does ADP-ribosylation alter the function of specific proteins and what is the effect on cell physiology? Most recently, the Hottiger-laboratory has studied the patterns of ADP-ribosylation using new systems biology approaches such as ADP-ribose specific high-resolution and quantitative mass spectrometry.

Website: http://www.dmmd.uzh.ch/en/research/hottiger.html

Selected publications:

Bisceglie L, Bartolomei G and Hottiger MO (2017) ADP-ribose-specific chromatin-affinity purification for investigating genome-wide or locus-specific chromatin ADP-ribosylation. Nature Protocols Sep;12(9):1951-1961.

Bilan V, Selevsek N, Kistemaker HAV, Abplanalp J, Feurer R, Filippov DV and Hottiger MO (2017) New quantitative mass spectrometry approaches reveal different ADP-ribosylation phases dependent on the levels of oxidative stress. Molecular & Cellular Proteomics May;16(5):949-958.

Bilan V, Leutert M, Nanni P, Panse C, Hottiger MO (2017) Combining Higher-Energy collision dissociation and electron-transfer/higher energy collision dissociation fragmentation in a product-dependent manner confidently assigns proteomewide ADP-ribose acceptor Sites. Analytical Chemistry Feb 7;89(3):1523-1530.

Martello R, Leutert M, Jungmichel S, Bilan V, Larsen SC, Young C, Hottiger MO and Nielsen ML (2016) Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue. Nature Communications Sep 30;7:12917. doi:

Leutert M, Pedrioli DML and Hottiger MO (2016) Identification of PARP-specific ADP-ribosylation targets reveals a regulatory function for ADP-ribosylation in transcription elongation. Molecular Cell Jul 21;63(2):181-183.

Hottiger MO (2015) SnapShot: ADP-ribosylation signaling. Molecular Cell Jun 18;58(6):1134-1134.e1.