As a PhD student in The University of Hong Kong, it would be an honour for me to join the Forum to meet Shaw Laureates and world-class scientists in different fields. Although I am personally interested in the Life Sciences and Medicine field, it would also be a great opportunity to meet the Laureates from other fields of research and understand their research mindsets. My project involves many different areas in the life sciences, including immunology, neuroscience and structural biology. I believe the participating Shaw Laureates would be able to inspire me to pursue a career in academia and help me build a resilient mindset that is crucial for being a successful researcher.

The University of Hong Kong

Multiple Sclerosis (MS) is an unpredictable and chronic autoimmune disease that gravely affects the central nervous system (CNS). It is often characterised by neuroinflammation and demyelination of neurons. Currently, there is no cure for MS, and patients suffer from various degrees of physical incapacitation and cognitive impairment. Recent advancements in chimeric antigen receptor (CAR) technology and immunotherapy provide an opportunity for engineering immune cells for MS treatment. This study will engineer lineage-negative hematopoietic stem and progenitor cells (Lin- HSPCs) with a CAR construct to generate CD19-targeting anti-inflammatory CAR-microglia. The CAR construct will be validated in vitro using murine microglia, murine B-cell, and HEK-Blue reporter cell lines. Subsequently, an experimental autoimmune encephalomyelitis (EAE) mice model induced by myelin oligodendrocyte glycoprotein (MOG) will be used to study the CAR-microglia’s effects in vivo. After myeloablative conditioning, injecting the engineered Lin- HSPCs into the CNS of EAE mice can allow cells to repopulate as microglia in the brain environment. The CAR-microglia aim to phagocytose CD19+ autoreactive B-cells that play a pathogenic role in MS and simultaneously maintain an anti-inflammatory CNS environment. Overall, this study hopes to contribute to the immunology and neuroscience fields by developing a tailorable and novel therapeutic approach using CAR-microglia.