Molecular Medicine Partnership Unit

The MMPU is a joint venture between the Medical Faculty of the University of Heidelberg and the European Molecular Biology Laboratory (EMBL).

Cholesterol Regulation

Rainer Pepperkok and Heiko Runz

MMPU Group 2007 – 2014

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.


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

Systematic Cell-Based Phenotyping of Missense Alleles.
Thormählen AS, Runz H.
Methods Mol Biol. 2017;1601:215-228. doi: 10.1007/978-1-4939-6960-9_17.PMID:28470529

Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells.
Ebrahimi-Fakhari D, Wahlster L, Bartz F, Werenbeck-Ueding J, Praggastis M, Zhang J, Joggerst-Thomalla B, Theiss S, Grimm D, Ory DS, Runz H.
Hum Mol Genet. 2016 Aug 15;25(16):3588-3599. doi: 10.1093/hmg/ddw204. Epub 2016 Jul 4.PMID:27378690

Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for LDLR and Myocardial Infarction.
Thormaehlen AS, Schuberth C, Won HH, Blattmann P, Joggerst-Thomalla B, Theiss S, Asselta R, Duga S, Merlini PA, Ardissino D, Lander ES, Gabriel S, Rader DJ, Peloso GM, Pepperkok R, Kathiresan S, Runz H.
PLoS Genet. 2015 Feb 3;11(2):e1004855. doi: 10.1371/journal.pgen.1004855. eCollection 2015 Feb.PMID:25647241

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

Peter Blattmann, PhD Student
Postdoc ETH Zurich

Luise Kern, PhD Student

Brigitte Joggerst

Rainer Pepperkok, PhD
Group Leader

Heiko Runz, MD
Group Leader
now:Medical Director Genetics, Biogen Inc., Cambridge, MA, 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)
now: LMU Munich Germany

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

Heiko Runz and Rainer Pepperkok