I am a molecular cell biologist, working at Princess Máxima Center in Utrecht.
In my research, I aim to gain mechanistic understanding on the preservation of neuronal health during aging and in disease. Here, I particularly focus on the so-called the cell type-specific protein quality control systems (e.g., the molecular chaperones), which assist proteins in attaining their functional conformations or guide misfolded proteins for cellular clearance; processes that are markedly affected in Huntington’s disease leading to clumping of misfolded, mutant huntingtin proteins into large inclusions and neurodegeneration. Within my research group, we integrate a large variety of approaches to provide mechanistic insights into the processes of mHTT aggregation and protein quality control in Huntington’s Disease and other aging-related disorders. In addition to biochemical approaches, we employ a fluorescent (super-resolution) microscopy method to study the formation and maturation of mutant Huntingtin (mHTT) aggregates as well as their association with chaperones.
Following completion of my PhD at Utrecht University, I received postdoctoral training in the laboratory of Prof. Judith Frydman (Stanford University, CA, USA), a leading expert on protein folding and protein quality control in health and disease. Additional training on protein folding stress, particularly at the endoplasmic reticulum, in health and proteinopathies was obtained in the lab of Prof. Ineke Braakman (Utrecht University). Subsequently, I continued my training in the lab of Prof. Jan Hoeijmakers (Princess Máxima Center Utrecht), where I studied the contribution of DNA damage-induced transcription stress and aging to the onset and pathology of protein aggregation diseases.
Within the CUREQ consortium, I am one of the co-applicants involved in WP4, aimed at the discovery of novel modulators of disease onset and progression. We previously demonstrated that a particular chaperone, the chaperonin complex TRiC/CCT, is critical in maintaining a healthy and soluble cellular proteome, while its expression is drastically reduced during brain aging and in HD. To follow-up on these findings, Carolina Konrdorfer-Rangel, our CureQ PhD candidate, will here aim to uncover and augment the mode-of-action by which chaperones, particularly the chaperonin TRiC/CCT, suppress mHTT aggregation and associated neurodegeneration.