GABAergic interneurons are involved in balancing the stimulation and inhibition in the brain, a balance that when disturbed can lead to several neurodegenerative and neuropsychiatric diseases. The overall purpose of our research is to create new and improved protocols to generate specific and disease-relevant interneurons using direct reprogramming.
Our research uses advanced technology to generate neurons from novel cell sources and to extensively define the subtype and function of the generated neurons and their potential for therapeutic use for several neurological and neuropsychiatric disorders. For this, we are applying reprogramming technology in in-vivo models or human stem cell culture systems, together with electrophysiology, RNA sequencing, tracing technologies, and cell-specific manipulation.
IN VIVO CONVERSION OF RESIDENT GLIA INTO FUNCTIONAL NEURONS
Direct neural reprogramming is an emerging field of research where a somatic cell, such as skin cells can be turned into a functional neuron by overexpressing specific transcription factors. Direct conversion offers a possibility for brain repair in situ as there is no stem cell intermediate formed in the transition.
In our lab, we use transgenic mouse models as well as human-derived tissue for direct reprogramming and functional analysis. We have shown that GABAergic interneurons can be generated in the living brain from endogenous glia using overexpression of specific transcription factors. Now we are focused on exploring these interneurons further by assessing the subtype specificity, synaptic integration, and functional maturity.
HUMAN GLIA CONVERSION INTO GABAERGIC INTERNEURONS
Direct conversion of human somatic cells into interneurons
This technique allows the generation of neurons, known as induced neurons (iN), and has today been established also on human cells such as fibroblasts. iNs offer a shortcut over induced pluripotent stem cells (iPSC) for generating patient and disease-specific neurons as well as various subtypes.
In our lab, we focus on generating subtype-specific GABAergic interneurons from skin fibroblasts from healthy controls and patients with interneuron diseases using improved reprogramming protocol and with functional specificity. In addition, we are also working on reprogramming human glial cells into functional interneurons.