Dr Marine Krzisch

Mounting evidence suggests a role of glial cells in a number of neurological diseases, including neurodegenerative diseases, however their exact involvement remains unclear. Animal models, while widely used, typically fail to fully mimic neurological disease, highlighting the need to use human cell-based models.

My laboratory focuses on deciphering the disease-relevant phenotypes of microglia and astrocytes and their effect on neurons in neurological diseases such as autism, schizophrenia, Alzheimer’s and Parkinson’s disease. I use human pluripotent stem cell (hPSC)-derived microglia or astrocytes cultured in isolation or with hPSC-derived neurons to probe the cellular and physiological alterations of these cells and determine molecular mechanisms that could be targeted therapeutically. These hPSC are either derived from patients or carry disease-linked mutations.

To validate my findings and provide more physiologically-relevant models for the characterization of patient-derived microglia, I use two groundbreaking models: the insertion of hPSC-derived myeloid precursors into human brain organoids, and the transplantation of hPSC-derived myeloid precursors into the mouse brain. These precursors differentiate into human microglia that recapitulate the physiological properties of microglia in the human brain more closely than 2-dimensional cultures. Because my models are human cell-based, my research will deliver findings that should be more easily translated to the clinic.