Inositol pyrophosphate signaling revealed with chemical tools

Cells are able to modulate a range of processes according to the external environment and internal sources, by integrating signaling cues with their metabolic status. The diphosphoinositol polyphosphates (PP-InsPs) are a unique group of highly phosphorylated messengers known to control glucose uptake, insulin signaling, and energy homeostasis, and provide an important link between signaling and metabolic networks. It is thought that PP-InsPs exert their effects as allosteric small molecule regulators and via pyrophosphorylation of protein substrates, but most details in PP-InsP signaling have thus far remained elusive.

Our group is taking chemical approaches to uncover the molecular mechanisms in PP-InsP signaling. We have applied non-hydrolyzable PP-InsP analogs for the affinity purification of inositol polyphosphate binding proteins. In parallel, we developed new strategies to detect protein pyrophosphorylation in complex samples using mass spectrometry. These methods, combined with improved biochemical and analytical tools to probe inositol phosphate interconversion, are now providing the molecular details underlying the pleiotropic functions of PP-InsPs messengers in eukaryotic cells.

Education

2005: Ph.D. in Chemistry, University of California at Berkeley; Advisors: Prof. Kenneth N. Raymond and Prof. Robert G. Bergman

2001: Diplom in Chemistry, Universität Würzburg, Germany; Advisors: Prof. Helmut Werner and Prof. John Arnold

Employment

2015–present: Professor, Leibniz-Forschungsinstitut für Molekular Pharmakologie und Humboldt-Universität zu Berlin 2010–2015: Assistant Professor, Princeton University, Princeton, NJ, USA

2006–2010: Postdoctoral Fellow, University of California at San Francisco, Laboratory of Prof. Kevan M. Shokat, San Francisco, CA, USA

2001–2005: Graduate Student, University of California at Berkeley, Laboratories of Prof. Kenneth N. Raymond and Prof. Robert G. Bergman, Berkeley, CA, USA

2000–2001: Visiting Scholar/Diploma Student, University of California at Berkeley, Laboratory of Prof. John Arnold, Berkeley, CA, USA

Honors

NIH Director’s New Innovator Award, 2013 
Rita Allen Scholar Award, 2013
Kimmel Scholar Award, 2013 
Thieme Chemistry Journals Award, 2012 
NIH Pathway to Independence Award, 2009–2013 
Fastrack Program, Robert Bosch Stiftung, 2007–2009 
Schering Stiftung Postdoctoral Fellowship, 2007–2009 
Young Investigator Award (ACS Inorganic Division), 2005 
Bayer AG Fellowship, 2000–2001 
Studienstiftung des Deutschen Volkes, 1998–2001