Prof. Christine Mummery: Understanding cardiovascular disease through human pluripotent stem cells

Head of the group:  Professor Christine Mummery 

Research Scientists: Prof. Robert Passier,  Dr. Christian FreundDr Karine RaymondDr. Leon Tertoolen
PhDs: Ruben van HeldenBerend van Meer, Jeroen Stein
Technicians: ing. Marga Boumaing. Saskia van der Wal-Maas

Research focus concerns cardiovascular development and disease models based on human pluripotent stem cells (hPSC). Immediate interests are on developing biophysical techniques for characterization and functional analysis of cardiovascular cells from hPSC with the ultimate aim of understanding underlying disease mechanisms and drugs for treatment through bioassays. The interest derives from a long-standing fascination on how differentiation choices are made in development and the roles played by growth factors. With the development of human iPS cells by reprogramming somatic cells from patients, enthusiasm for potential clinical applications has grown, particularly in using these cells to identify personalized drug targets and sensitivities and ways to correct disease phenotypes. Aside from cardiomyocytes, endothelial cells and vascular smooth muscle cells take a central role in the research, again in a clinical setting where we study a hemorrhaging disease (HHT) caused by mutations in TGFß receptors. We revealed several important mechanism underlying the disease and investigate several candidate drugs now being prescribed to patients. Through collaboration with clinicians in Leiden and Utrecht and engineers in UTwente, we are currently implementing methods for creating synthetic 2-D and 3-D normal and (genetically) diseased vascular and myocardial tissue. These study areas form part of the NWA on personalized medicine, early diagnosis and regenerative medicine.

Current research grants (selection)

EU FP7 2013-2017 Plurimes. Mesodermal tissue repair using pluripotent stem cells (450k€)
CVON (Cardiovascular Onderzoek Nederland) NHS. HUSTCARE 2013-2018. Cardiac repair. Co-PI (350k€).  
European Research Council Advanced Grant 2013-2018. Human pluripotent stem cells: the new heart patient. Personal grant/PI (2.5 M€)
Muller Foundation (2014-2019). hiPSC models for vascular disease. PI (750k€)
ERARE-CVD: CPVT heart disease models co-PI (350k€).
ZonMW MKMD (2017-2020) hIPSC as models for cardiac disease. PI (350k€)
Interreg: Biomat microfluidic chips (2018-2020).PI (450k€).
TK-LSH (2018-2020):hiPSC model of arrhythmia. PI (90k€)
Ministry of Education, Culture and Science NWO Gravity Grant 2017 (2017-2027) Netherlands Organ on Chip Initiative. PI (18.8 mlj €)

Most important scientific publications in the past six years

1.  Davis, R. P., Casini, S., Hoekstra, M., Remme, C. A., Dambrot, C., Salvatori, D…Mummery C.L. Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease. Circulation, 2012; 125(25), 3079–3091. IF 19.3 Cite 154

2.  Bellin M, Davis RP, Casini S, D’Aniello C, Haas J, Ward-van Oostwaard D, Tertoolen LGJ, Jung CB, Elliott DA, Welling A, Laugwitz KL, Moretti A, Mummery CL Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome. EMBO J  2013 32, 3161–3175. IF 9.8; Cit 68

3.  V.V. Orlova, F.E. van den Hil, S. Petrus-Reurer, Y. Drabsch, P.ten Dijke, C.L. Mummery. Endothelial Cells and Pericytes from human Pluripotent Stem Cells: methods for efficient generation, expansion and examination of functional competence. Nature Protocols 2014 9, 1514-1531 doi:10.1038/nprot.2014.102  IF 10.0; Cit 43

4.  Zhang M, D’Aniello C, Verkerk A, Wrobel E, Frank S, Ward-van Oostwaard D, Piccini I, Freund C, Rao J,

Seebohm G, Atsma D, Schulze-Bahr E, Mummery CL, Greber B, Bellin M. Recessive cardiac phenotypes in iPS cell models of Jervell and Lange-Nielsen Syndrome: disease mechanisms and pharmacological rescue. Proc Natl Acad Sci U S A. 2014; 111(50):E5383-92.  IF: 9.7; Cit: 46

5.  Birket MJ, Ribeiro MC, Verkerk AO, Ward D, Leitoguinho AR, den Hartogh SC, Orlova VV, Devalla HD, Schwach V, Bellin M , Passier R, Mummery CL. Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells. Nat Biotechnol. 2015; 33(9):970-9. IF: 41.5; Cit: 52

6.  Devalla HD, Schwach V, Ford JW, Milnes JT, El-Haou S, Jackson C, Gkatzis K, Elliott DA, Chuva de Sousa Lopes SM, Mummery CL, Verkerk AO, Passier R. EMBO Mol Med. 2015 Apr;7(4):394-410.  IF 9.2; Cit: 49

7.  Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature. 2016 Aug 11;536(7615):238. doi: 10.1038/nature17982. IF 40.1; Cit 131

8.  Passier, R., Orlova, V., Mummery, C., 2016. Complex Tissue and Disease Modeling using hiPSCs. Cell Stem Cell 18, 309–321  IF  23.1  Cit 24

9.  Sala L, Yu Z, Ward-van Oostwaard D, van Veldhoven JP, Moretti A, Laugwitz KL, Mummery CL, IJzerman AP, Bellin M. A new hERG allosteric modulator rescues genetic and drug-induced long-QT syndrome phenotypes in cardiomyocytes from isogenic pairs of patient induced pluripotent stem cells. EMBO Mol Med. 2016 Sep 1;8(9):1065-81.  IF 9.2 Cit 11

10.  Roost MS, Slieker RC, Bialecka M, van Iperen L, Gomes Fernandes MM, He N, Suchiman HED, Szuhai K, Carlotti F, de Koning EJP, Mummery CL, Heijmans BT, Chuva de Sousa Lopes SM. DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells. Nat Commun. 2017 Oct 13;8(1):908. doi: 10.1038/s41467-017-01077-3. IF 12.1 Cit 0 

Five most important societal publications and/or other societal outputs in the past six years

1 ''Stem Cells: Scientific Fact and Fiction'' Elsevier 2014:  general guide to stem cells for clinicians, ethicists, lawyers patients and lay public

2 EUROSTEMCELLS Consortium: Promoting stem cell knowledge and collaboration in Europe

3 Ergo Sum: Science, Art and Stem cells (2015): BioArt exhibition Boerhave Museum (iPSC lab and Charlotte Jarvis, UK)

4 Lowlands University 2015: Public lecture pop festival: Stem cells: healthy aging or immortality?

5 NEMO Science Museum Amsterdam: Public lecture on cloning and future health

6 Host high school students (10-15) annually for Profile Work Project (PWS) and ''Design Thinking Thesis''

7 Honours Academy, University of Leiden