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Yichen Li


Postgraduate Student

Research summary

Schizophrenia is a devastating mental disorder that affects about 1% of the total population. Patients with adolescent onset schizophrenia (AOS) suffer from more severe symptoms and have a worse prognosis. The aetiology of schizophrenia is largely unknown. However, it is widely accepted, in part, as a neurodevelopmental disorder with a multifactorial genetic and environmental (e.g. inflammation) basis. It has been difficult to produce adequate animal models, therefore I am using in vitro stem cell strategies to study human neural development in AOS. The human olfactory mucosa harbours stem cells that give rise to neurons. These olfactory stem cells (OSCs) in vitro may provide an accessible resource for studying the molecular mechanisms that underlie the abnormal neurodevelopment in schizophrenia. Using this material, I assess the basic stem cell properties, as well as proliferation and migration, which were previously shown to be aberrantly regulated in OSCs from adult onset schizophrenia. From the same subjects as OSCs, I also obtained skin biopsies to undertake cellular reprogramming to generate patient-derived induced pluripotent stem cells (iPSCs) with the ultimate aim of in vitro generation of human neurons and microglia. The lineage conversion from iPSCs to neurons can be done via over-expression of key transcription factors during neurogenesis, such as NGN2. I assess a series of essential features of iPSC-derived layer III pyramidal neurons, co-cultured with or without iPSC-derived microglia, from three pairs of patients with AOS and healthy controls. My aim is to identify disease-associated phenotypes and eventually dissect out convergent pathways shared between patients with different genetic background.

Bibliography

I read Biochemistry at HAN University of Applied Sciences in The Netherlands and Neuroscience at Imperial College London in UK. After graduation I worked as a research assistant at University of Southern California, where I screened compounds on iPSC-derived motor neurons for the treatment of Amyotrophic Lateral Sclerosis. At the moment, I am a D.Phil candidate (3rd year) and a Clarendon scholar at DPAG, associated with St. Anne's College in Oxford.


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