Stem cells models for studies of neurodegenerative diseases

Illustration of stem cells neurodegerative disesesResearch focus

Our research activities are focused on disease modeling using induced pluripotent stem cells (iPSC) from patients and their CRISPR-Cas9 gene edited controls. Our research focus is on Alzheimer’s disease (AD), Frontotemporal dementia (FTD) and glaucoma.

Within AD and FTD we are investigating cell type specific pathologies in neurons, astrocytes and microglia. We are especially keen on understanding overlapping dysfunctions amongst different types of dementia and identification of key players in disease pathways. We believe that comprehensive understanding of such molecular commonalities may provide opportunities for novel interventions that are beneficial for an array of related diseases facilitating cost effective drug development. Explorations of disease pathways instead of disease-linked proteins will not only further the knowledge of disease development and progression, but also provide novel angles and targets for drug development. This part of our research is embedded in the BrainStem and NeuroStem projects (for more information: https://brainstem.dk/).

Within glaucoma we are specifically interested in the degeneration of retinal ganglion cells (RGCs) and their trophic support of Mueller cells (MCs). We are investigating this intrinsic inter-relation of MCs and RGCs in close collaboration with the clinic and Professor MSO Miriam Kolko.

Illustration of cell division

Current projects

Our main research focus is on Frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Here we differentiate our cellular models into neurons, astrocytes and microglia and assess cellular phenotypes compared to their isogenic controls. BrainStem and NeuroStem (Innovation Foundation Denmark) support the disease in the dish modelling of both FTD and AD.We are particularly interested in the inflammatory component of neurodegeneration and investigate the role of specific single nucleotide polymorphisms (SNPs) related to the innate immune system in sporadic AD funded by Novo Nordisk Foundation(GliAD).

Additionally, we are investigating the consequences and treatment options in rare childhood epilepsies in collaboration with Rikke Møller at the Danish epilepsy center. This project implements CRISPR/Cas9 editing of healthy iPSC to generate loss and gain of function mutations in CACNA1A Novo Nordisk Foundation(PREMED).

Recently a Lunbeck collaborative project was awarded to Martin Røssel Larsen  https://lundbeckfonden.com/en/researchstories/mini-brains-to-shed-light-on-nervous-disorders in which I am co-applicant and partner together with Madelaine Lancester. Within this grant we will make several iPSC lines of schizophrenia patients and analyse their cerebral organoids.

Our glaucoma research is currently focusing on generation of RGCs in 3D optic cups and this work is supported by the Danish Ophthalmology Society via Miriam Kolko

Furthermore, we are collaborating with Poul Hyttel on a project to evaluate the dog as a model for AD research and compare iPSC derived neurons from dogs with canine cognitive deficits (CCD) to the human AD iPSC derived neurons (funded by the Dansk Forskningsråd, PI Poul Hyttel). Last but not least, we are collaborating with Hans Wandall and Jakob Barslev Sørensen on glycolysation changes in AD and Epilepsy, respectively. Both are funded via Lundbeck Foundation.

Research Funding

logo innovationsfonden logo novo nordisk fonden
alzheimerforeningen - logo logo lundbeck fonden

Selected Publications