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Molecular Medicine Partnership UnitResearch Groups

Former MMPU Research Group Cholesterol Regulation

MMPU Group 2007 - 2014

Rainer Pepperkok and Heiko Runz

Heiko Runz and Rainer Pepperkok

Project Summary

Our research interest aims to identify and functionally characterize novel factors regulating cellular cholesterol metabolism. Our long-term goals are a better molecular understanding of elevated blood cholesterol levels (hypercholesterolemia) and Niemann-Pick Type C (NPC) disease with the perspectives to develop novel diagnostic and therapeutic tools. The experimental approaches we use are (i) identification of candidate genes by disease related gene expression analyses, (ii) cell biological characterization of candidate genes with respect to cholesterol metabolism and (iii) analysis of possible gene defects in patient samples.

Background

Cholesterol levels in animal cells need to be tightly balanced. Within recent years, a network of proteins has been identified that keep cellular cholesterol levels to narrow limits. The concerted interplay of these proteins confers that reduced levels of membrane-bound cholesterol may activate the expression of genes necessary to increase cholesterol levels in cells, e.g. by uptake of low-density lipoprotein (LDL)-bound cholesterol or cholesterol biosynthesis. It is, however, assumed that only a limited number of proteins involved in cellular cholesterol regulation have been identified to date.

Selected Publications

Transmembrane Protein 55B Is a Novel Regulator of Cellular Cholesterol Metabolism.
Medina MW, Bauzon F, Naidoo D, Theusch E, Stevens K, Schilde J, Schubert C, Mangravite LM, Rudel LL, Temel RE, Runz H, Krauss RM.
Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1917-23. doi: 10.1161/ATVBAHA.113.302806. Epub 2014 Jul 17. PMID:25035345

Sequencing of a patient with balanced chromosome abnormalities and neurodevelopmental disease identifies disruption of multiple high risk loci by structural variation.
Blake J, Riddell A, Theiss S, Gonzalez AP, Haase B, Jauch A, Janssen JW, Ibberson D, Pavlinic D, Moog U, Benes V, Runz H.
PLoS One. 2014 Mar 13;9(3):e90894. doi: 10.1371/journal.pone.0090894. eCollection 2014. PMID:24625750

Characterization of drug-induced transcriptional modules: towards drug repositioning and functional understanding
Iskar M, Zeller G, Blattmann P, Campillos M, Kuhn M, Kaminska KH, Runz H, Gavin AC, Pepperkok R, van Noort V, Bork P.
Mol Syst Biol. 2013 Apr 30;9:662. doi: 10.1038/msb.2013.20

RNAi-based functional profiling of loci from blood lipid genome-wide association studies identifies genes with cholesterol-regulatory functions.
Blattmann P, Schuberth C, Pepperkok R, Runz H.
PLOS Genetics 2013, Feb;9(2):e1003338. doi: 10.1371/journal.pgen.1003338. Epub 2013 Feb 28.

Identification of cholesterol-regulating genes by targeted RNAi-screening.
Bartz F, Kern L, Erz D, Zhu M, Gilbert D, Meinhof T, Wirkner U, Erfle H, Muckenthaler M, Pepperkok R,
Runz H
Cell Metabolism 10, 8 July 2009, 63-75

DetecTiff: A novel image analysis routine for high content screening microscopy
Gilbert D, Meinhof T, Pepperkok R, Runz H.
Journal of Biomolecular Screening 2009 Sep;14(8):944-55. Epub 2009 Jul 29

Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G
Runz H, Miura K, Weiss M and Pepperkok R.
EMBO J. 2006, 25(13), 2953-65.

Inhibition of intracellular cholesterol transport alters presenilin localization and APP processing in neuronal cells
Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R and Hartmann T.
J. Neuroscience 2002, 22(5), 1679-89

 

Group members

in alphabetical order

Fabian Bartz, PhD Student
bartz.fabian@googlemail.com

Peter Blattmann, PhD Student
Postdoc ETH Zurich

Luise Kern, PhD Student

 

Brigitte Joggerst
Technician

Rainer Pepperkok, PhD
Group Leader
rainer.pepperkok@embl.de

 

Heiko Runz, MD
Group Leader
heiko.runz@merck.com
now:Director of Genetics, Merck Research Labs, Boston USA

 

Christian Schuberth, PhD
Advanced Imaging Platform, Muenster University Clinics

Carolina Taengemo, PhD
Centre for Cellular Imaging (CCI) Sahlgrenska Academy University of Gothenburg, Sweden

 

Aenne Solvejg Thormählen
MD student (HRCMM Junior Career Fellowship JCF)
aenne.thormaehlen@arcor.de
now: LMU Munich Germany

 

Anthi Trasta
PhD student (EMBL International PhD Programme - EIPP)