Postdoc Parkinson’s disease (PD) disease mechanisms

Parkinson’s disease (PD) encompasses a spectrum of motor and cognitive/psychiatric symptoms. Dementia may occur early, before parkinsonism, as in Dementia with Lewy bodies (DLB), or later in the course of the disease (PDD). Mutations in GBA1 and LRRK2 are the most common genetic risk factors. Up to 80% of cases are genetically sporadic. Although many upstream pathways may cause PD, the downstream consequence will be an end-stage α-synucleinopathy in most cases.

To overcome the heterogeneity dilemma that hampers drug development, here, we implemented a translational approach that integrates within-subject clinical and pathological information with morphological and molecular knowledge of induced pluripotent stem cells (iPSC) and human brain tissue samples of PD(D)/DLB patients to identify molecular profiles and drug targets.

We collect postmortem skin biopsies and brain tissue from PD patients in close collobariton with the Netherlands Brain bank. In parallel, we prospectively collect skin biopsies from well-phenotyped Parkinson patients (ProPARK cohort). We generated well-defined iPSC. Using advanced genomics and proteomics we aim to identify molecular profiles in these iPSC lines and brains. In addition, we will use spatial trancriptomics to define molecular mechanisms underlying selective vulnerability to alpha-synuclein pathology. This will eventually help us to identify and validate druggable targets for molecular subtypes in PD(D) using a disease subtype classification based on pathology or dysregulated cell biology.

As a postdoc, you will closely work with the PhD students and research technicians within the Clinical Neuroanatomy and Biobanking (CNAB) section, withing the dept. of Anatomy and Neurosciences at VUmc to study disease mechanisms involved in early-stage Parkinson's disease. You will characterize and study disease mechanisms using fibroblasts, iPSC-derived dopaminergic neurons and human brain tissue samples using live-cell imaging or STED-microscopy, and multi-omics techniques. Within the contect of the JPND project, you will study molecular mechanisms underlying selective vulnerability in brain tissue samples from patients in early and late stage disease using spatial transcriptomics and RNAscope.

You will contribute to a EU JPND project '4DPD-Omics' focused on the identification of cell type-specific vulnerability and tolerance mechanisms in Parkinson's disease.

Techniques: neuroanatomy and neuropathology of neurodegenerative disorders, fibroblast and IPSC cell culture, protoeomics, genomics, cellomics, spatial transcriptomics and high-end 3D microscopy.

As postdoc, you will work in the section Clinical Neuroanatomy and Biobanking (CNAB) at the department of Anatomy and Neurosciences, Amsterdam UMC, location VUmc, Amsterdam. Our mission is to unravel cellular disease mechanisms in Parkinson's and related disorders in order to develop early diagnostics tools and identify drug targets for novel treatment paradigms.

Clinical Neuroanatomy & Biobanking – Anatomie en Neurowetenschappen (anatomy-neurosciences.com)
You will contribute to the program Neurodegeneration and Amsterdam Parkinson and Movement Disorder Centre.

Neurodegeneration (amsterdamumc.org)