Willianne Vonk Email & Phone Number

Utrecht, Netherlands

Utrecht Area, Netherlands

In my research, I aim to gain a mechanistic understanding of the preservation of neural plasticity and its attenuation with age and in disease, with a focus on cell type-specific protein quality control strategies managing (stress-induced) protein misfolding and aggregation and neurodegenerationBesides managing my own research team, I have co-initiated the postdoc association platform at the Princess Maxima Center.

Investigating proteostasis machineries in neural stem cells in health and disease- Expanded my line of research and initiated new (inter)national collaborations- Applied my expertise to ongoing research in the lab, thereby aided in advancing projects of other lab members- Supervised BSc and MSc students- Organized national scientific meeting (17th Annual Dutch Chaperone Meeting)- Co-organized BSc course Protein Folding and Assembly for Bachelor program Molecular Life Sciences (MLS) at Utrecht University

Stanford, Ca, Usa

Investigating proteostasis systems in neurodegenerative disease pathologies- Set up a new and unique line of research within the lab/department, which laid the foundation for several projects in the lab- Supervisor for Science is Elementary (Teaching Science at elementary schools)- Mentor for Association for Women in Science (AWIS)- Co-supervisor beginning postdocs and PhD students

Successfully finalized Ph.D. work for publication

PhD research Understanding COMMD1 function: novel perspectives from in vitro and in vivo studiesCOMMD1 gene deletion is associated with a canine copper-overload disease. However, our knowledge on COMMD1 function is highly limited. The main objective of my PhD research was to increase our understanding of COMMD1 function. The obtained data demonstrated a general function for COMMD1 as scaffold protein regulating the stability and degradation of its client proteins. - I generated a hepatocyte-specific Commd1-deficient mouse model to gain more insight into the role of COMMD1 in copper homeostasis. Commd1 deficiency in mice only resulted in a progressive copper accumulation when dietary copper intake was increased, and provided the first genetic evidence for Commd1 to play an essential role in hepatic copper homeostasis. - I established an interaction between COMMD1 and the P-type copper transporter ATP7A. Mutations in ATP7A result in Menkes disease, a copper-deficiency disorder. Depletion of endogenous COMMD1 expression resulted in a less stable ATP7A protein with impaired copper transport function. Interestingly, overexpression of COMMD1 enhanced the expression and localization of ATP7A mutant proteins which are normally impaired in their function. Consequently, the ATP7A copper transport capacity of these mutants was partially restored by COMMD1. - Additionally, I identified an interaction between COMMD1 and the antioxidant Cu/Zn Superoxide Dismutase 1 (SOD1). COMMD1 impaired the SOD1 scavenging function as result of abrogated SOD1 maturation leading to enhanced cytotoxicity. - Since mutations in SOD1 are associated with the neurodegenerative disorder ALS, the effect of COMMD1 on ALS pathogenesis was examined. Binding of COMMD1 to SOD1 mutants induced the cytotoxic aggregate formation of mutant SOD1 proteins, and suggested an important function for COMMD1 in ALS disease onset and progression.

Business School Module: Performance Management

Phd

Msc, Biomedical Sciences