Role of protein homeostasis and the protein quality control system underlying atrial fibrillation
Bianca Brundel received her PhD from the University Medical Center Groningen, the Netherlands and was trained in molecular and cellular biology (VU, Amsterdam) and clinical pharmacology (UMCG). Bianca is professor at the physiology department at the Amsterdam UMC, location VU University Medical Center. Her research is focused on the molecular mechanisms driving proteostasis derailment and pathophysiology of cardiac diseases, including atrial fibrillation and cardiomyopathies. Molecular findings are used to identify novel druggable targets. Her laboratory utilizes experimental cardiomyocyte and Drosophila cardiac disease models in combination with genetic and pharmacological manipulations. She is project leader of translational research projects and founder of the Atrial Fibrillation Innovation Platform, to promote translational studies in collaboration with patients, and the Cardiac Arrhythmia Lab to develop bio-electrical diagnostic tools. As such, she contributed to forwarding candidate drugs into (pre-)clinical proof-of-principle studies.
Zhang D, Hu X, Li J, Liu J, Baks-te Bulte L, Wiersma M, Malik N, Van Marion D, Tolouee M, Hoogstra-Berends F, Lanters E, Van Roon A, De Vries A, Pijnappels D, De Groot N, Henning R, Brundel BJJM. DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental Atrial Fibrillation. Nature Communications. 2019; in press
Iuso A*, Wiersma M*, … Brundel BJJM, Haas D, Sibon OCM, Anikster Y. Mutations in phosphopantothenoylcystein synthetase (PPCS) cause dilated cardiomyopathy. American Journal of Human Genetics. 2018;102(6):1018-1030. PMID: 29754768, doi: 10.1016/j.ajhg.2018.03.022.
Meijering RAM, Wiersma M, Zhang D, Lanters EAH, Hoogstra-Berends F, Scholma J, Diks S, Qi X, de Groot NMS, Nattel S, Henning RH, Brundel BJJM. The application of kinomic array analysis to screen for altered kinases in atrial fibrillation remodeling. Heart Rhythm. 2018;15(11):1708-1716. PMID: 29902583, doi: 10.1016/j.hrthm.2018.06.014
Henning RH & Brundel BJJM: Proteostasis in cardiac health and disease. Nature Reviews Cardiology 2017. PMID 28660894, doi: 10.1038/nrcardio.2017.89
Nolte I, Munoz ML, .. Brundel BJJM, De Geus E, Snieder H. VgHRV GWAS. Nature Communication 2017. PMID 28613276, doi: 10.1038/ncomms15805
Wiersma M, Meijering RAM, .. Sibon OCM, Henning RH, Nattel S, Brundel BJJM. Endoplasmic Reticulum Stress is associated with autophagy and cardiomyocyte remodeling in Atrial Fibrillation. JAHA. 20176(10). PMID: 29066441, doi: 10.1161/JAHA.117.006458
Zhang D, Hu X, Henning RH, Brundel BJJM. Keeping up the balance: role of HDACs in cardiac proteostasis and therapeutic implications for atrial fibrillation. Cardiovasc Res. 2016;109:519-26. PMID: 26645980, doi: 10.1093/cvr/cvv265
Zhang D, Wu CT, Qi X, Meijering RAM, Hoogstra-Berends F, Tadevosyan A, Cubukcuoglu Deniz G, Durdu S, Akar AR, Sibon OCM, Nattel S, Henning RH, Brundel BJJM. Activation of HDAC6 induces contractile dysfunction in experimental and human Atrial Fibrillation. Circulation 2014; 129:346-58. PMID 24146251
Qi XY, Diness JG, Brundel BJJM, Zhou XB, Naud P, Wu CT, Huang H, Harada M, Aflaki M, Dobrev D, Grunnet M, Nattel S. Circulation. 2014;129(4):430-40. PMID: 24190961, doi: 10.1161/CIRCULATIONAHA.113.003019.
Den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM et al. Heart rate-associated loci and their effects on conduction. Nature Genetics 2013; 45:621-31. PMID 23583979
ONGOING RESEARCH PROJECTS
2019-2020: ACS grant: LMNA mutations familial AF. Project leaders: Prof. B. Brundel (VUmc) and Dr. E. Creemers (AMC).
2019-2021: AFIP Foundation and Bayer: AF-ENERGY trial. Clinical drug study with Niagen in AF patients. Project leaders: Prof. B. Brundel (VUmc) and Prof. N. de Groot (EMC)
2019-2023: Medical Delta: Cardiac Arrhythmia Lab. Project leaders: Prof. N. de Groot (EMC), Prof. W. Serdijn (TuDelft), Prof. A.J. van der Veen (TuDelft)
2018-2019: ACS grant: Titin mutants as marker for AF. Project leaders: Prof. B. Brundel and Dr. JP van Tintelen (UMCU)
2018-2019: Coolsingel Foundation: Glutaminimize Atrial Fibrillation study. Clinical drug study with L-glutamine in AF patients. Project leaders: Prof. B. Brundel (VUmc) and Prof. N. de Groot (EMC)
2017-2021: CVON grant AFFIP: Atrial Fibrillation FIngerPrinting: Spotting bio-electrical markers to early recognize atrial fibrillation by the use of a bottom-up approach (AFFIP) Project leaders: Prof. Natasja de Groot (EMC) and Prof. Dr. B. Brundel (VUmc)
2015-2020: CVON grant DOSIS: Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches. Project leaders: Prof. J. van der Velden and Prof. R. de Boer (UMCG), PI Prof. Dr. B. Brundel (VUmc), www.cvon-dosis.nl
2014-2019: Established investigator, Dutch Heart Foundation: REVersal of cardiomyocyte structural remodeling and Improvement of functional recoVEry in Atrial Fibrillation. REVIVE
2014-2018: LSH grant. HSF1 activators lower cardiomyocyte damage: towards a novel therapeutic approach to reverse Atrial Fibrillation. HALT&REVERSE (Consortium leader)
With: Dr. N. de Groot (EMC), Nyken BV, Dutch Heart Foundation
2014-2018: Dutch Heart Foundation funded grant: Juvenile Cardiomyopathy. Boosting chaperone networks to counteract juvenile DCM caused by chaperone mutations. (co-PI)
With: Prof. H. Kampinga (UMCG) and Prof. J. van der Velden (VUmc)