Brigitte van Zundert, Ph.D.

Biography

Brigitte

Brigitte van Zundert graduated as a Biochemist from the “Hogeschool West-Brabant”, (the Netherlands) (1993). She obtained her Master`s degree in Molecular Biology from the University of Utrecht (the Netherlands) (1996), while performing her thesis at the University of Massachusetts (Umass, Worcester, USA), which was focused on transcriptional regulation. In 1996, she moved to Chile, where she obtained her PhD degree in Molecular and Cell Biology from the University of Concepción (UDEC) (2002). Her thesis focused on the molecular mechanisms underlying glycine receptor clustering at synapses, for which she was awarded “the Best Doctoral Thesis” by the “Chilean Foundation for Cell Biology“. From 2002 to 2005, she received a 3 years duration joined post-doctoral training at the Massachusetts Institute of Technology (MIT) and Harvard Medical School, where she worked on two projects: (i) Role of synaptic glutamatergic receptors and their anchoring proteins during synapse development, and (ii) Characterization of early pathology in neonatal animal models of the adult neurodegenerative disease amyotrophic lateral sclerosis (ALS). In 2005, she started her independent laboratory at the UDEC, but moved in 2010 to the Center for Biomedical Research (CIB) – now Institute of Biomedical Sciences (ICB)- at the U. Andres Bello (UNAB, Santiago, Chile, where she is currently Full Professor. She was awarded with «The most outstanding young scientists 2010» by the «Chilean Society for Biology». Since 2017, she is also principal investigator at the Center of Aging and Regeneration (CARE) from the Pontifical Catholic University of Chile (CARE UC), and since February 2020 an Adjunct Professor at UMass Medical School (Worcester, USA).

Research Description

The laboratory of Dr. Brigitte van Zundert addresses cellular and molecular mechanisms underlying brain plasticity and neuroepigenetics in health (learning & memory) and in disease (ALS, frontotemporal dementia (FTD), Alzheimer’s disease (AD) and Huntington`s disease (HD)). The underlying premise of the studies in brain diseases is that the acquired knowledge will open avenues for developing effective diagnostic and therapeutic approaches to slow the progression and, more optimistically, to prevent, halt, or even revert the effects of these devastating neurodegenerative diseases. More recently, the laboratory of Dr. van Zundert has started to elucidate epigenetic mechanisms by which external factors (i.e. urban air pollution) contribute to disease pathogenesis and cognitive deficits. Dr. van Zundert has published >50 ISI papers, highlighting two recent publications in prestigious journals, one publication in Neuron (Arredondo et al., 2022) identifying polyphosphate as a critical factor in non-cell-autonomous motoneuron degeneration and a potential diagnostic and therapeutic target for ALS/FTD, and one publication in Brain (Bustos et al., 2017) demonstrating that epigenetic editing of the synaptic gene PSD95 improves cognition in aged and AD mice. To date, Dr. van Zundert has directed 22 Undergraduate/Master thesis students, 7 PhD thesis students and 8 Postdoctoral fellows. Currently, her laboratory comprises 2 Postdoctoral fellows, 5 PhD thesis students, 5 undergraduate students and 2 technicians. As a principal investigator her laboratory receives funding from national (FONDECYT and CONICYT-BASAL) and international (ALSA Association, FightMND) agencies.

Key Publications

  1. Arredondo C, Cefaliello C, Dyrda A, Jury N, Martinez P, Diaz I, Amaro A, Tran H, Morales D, Pertusa M, Stoica L, Fritz E, Corvalán D, Abarzúa S, Méndez-Ruette M, Fernández P, Rojas F, Sundaram Kumar M, Aguilar R, Almeida S, Weiss A, Bustos FJ, González-Nilo F, Otero C, Tevy MF, Bosco DA, Sáez JC, Kähne T, Gao F-B, Berry JD, Nicholson K, Sena-Esteves M, Madrid R, Varela D, Montecino M, Brown RH, van Zundert B*. Excessive release of inorganic phosphate by ALS/FTD astrocytes causes non-cell autonomous toxicity to motoneurons. Neuron 110, 1-15 (2022). (DOI: 10.1016/j.neuron.2022.02.010) (published online now).

 

  1. Bustos FJ, Ampuero E, Jury N, Aguilar R, Falahi F, Toledo J, Ahumada J, Lata J, Cubillos P, Henríquez B, Guerra MV, Stehberg J, Neve RL, Inestrosa NC, Wyneken U, Fuenzalida M, Härtel S, Sena-Esteves M, Varela-Nallar L, Rots MG*, Montecino M*, van Zundert B*. Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice. Brain (2017) Dec 1;140(12):3252-3268. doi: 10.1093/brain/awx272.

 

  1. Jury N, Abarzua S, Diaz I, Guerra MV, Ampuero E, Cubillos P, Martinez P, Herrera-Soto A, Arredondo C, Rojas F, Manterola M, Rojas A, Montecino M, Varela-Nallar L*, and van Zundert B*. Widespread loss of the silencing epigenetic mark H3K9me3 in astrocytes and neurons along with hippocampal-dependent cognitive impairment in C9orf72 BAC transgenic mice. Clinical Epigenetics (2020). Feb 18;12(1):32. doi: 10.1186/s13148-020-0816-9.

 

  1. Quezada E, Cappelli C, Diaz I, Jury N, Wightman N, Brown RH, Montecino M*, van Zundert B*. BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model. Clinical Epigenetics (2021) Mar 16;13(1):56. doi: 10.1186/s13148-021-01039-z.

 

  1. Calderón-Garcidueñas L, Herrera-Soto A, Jury N, Maher BA, González-Maciel A, Reynoso-Robles R, Ruiz-Rudolph P,Varela-Nallar L*, and van Zundert B*. Reduced repressive epigenetic marks and increased DNA damage in the brain of humans and mice exposed to particulate urban air pollution. Environmental Research (2020) Apr 183:109226. doi: 10.1016/j.envres.2020.109226

 

 

Link to complete list of Brigitte van Zundert´s published work:

https://pubmed.ncbi.nlm.nih.gov/?term=van+Zundert+B&sort=date