A Focus on Stem Cells
The laboratory of Kristen Brennand, PhD focuses on modeling psychiatric disorders using stem cell derived neurons. Schizophrenia (SCZD) is a debilitating psychiatric disorder. While its characteristic symptoms generally appear late in adolescence, SCZD is thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Though postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, abnormalities of neuronal organization, particularly in the cortex, have also been reported. Due in part to the lack of live patient material for study, the cellular and molecular mechanisms of disease initiation and progression remain unknown. Though aberrant migration of human neural progenitor cells (NPCs) and reduced connectivity of human neurons has been hypothesized to contribute to disease initiation, neither mechanism is understood in live human neurons.
Through clinical collaborations, the Brennand lab has obtained skin samples from well-characterized cohorts of children and adults with SCZD as well as samples from healthy controls. Having reprogrammed these skin cells into human induced pluripotent stem cells (hiPSCs) and directed these hiPSCs to undergo neural differentiation, we can generate near limitless quantities of live healthy and SCZD NPCs and neurons. By identifying differences between healthy and diseased neurons, we hope to elucidate the mechanisms that result in SCZD and to screen for new drugs with which to reverse the cellular defects contributing to disease.