Neural Cell Dysfunction in Aging and Neurodegeneration

The main aim of our research is to gain cellular, molecular and functional insights and understanding of neural aging and degeneration.

In this project we will use innovative technologies in the fields of stem cell biology, reprogramming and genome editing as well as in vivo approaches to study aging and neurodegenerative disorders.Our overarching hypothesis is that aged and diseased astroglial cells: astrocytes and neural stem cells, gain aberrant inflammatory and toxic functions detrimental to neurons and oligodendrocytes.To generate isogenic human neural cells predisposed to neurodegeneration we will use CRISPR/Cas9 genome engineering to introduce mutations known to cause neurodegenerative disorders and astrocytopathies in human pluripotent stem cells.Aged and diseased pluripotent cells or fibroblasts from patients will then be differentiated to neurons as well as glial cells using novel protocols I took part in developing or developed in my lab.

Next we will in detail analyze how aged and diseased astroglial cells affect neural cell function and survival.Furthermore, we will analyze transcriptional changes in mouse and human astroglial cells during aging and explore the potential to rejuvenate neurogenesis in aging and neurodegeneration.Results from these studies have the potential to be extremely important for how we perceive neural aging and degeneration and be the basis for novel therapeutic intervention.