Ming Ho Choi

My research focuses on the role of mitochondria–endoplasmic reticulum contact sites (MERCS) in Alzheimer’s disease (AD). These contact sites contain specialized protein complexes that regulate key cellular processes, and both their structure and function are altered in AD. A major goal of my work is to understand how changes in MERCS contribute to cellular dysfunction in AD and whether targeted modulation of these sites may offer therapeutic benefit.

Neuroinflammation is a prominent feature of AD progression and may precede amyloid-β deposition. NLRP3 inflammasome is a major driver of neuroinflammation and is known to assemble and activate at mitochondria–ER contact sites (MERCS) in peripheral immune cells, a process dependent on mitochondrial proteins. My current research examines how microglial MERCS regulate NLRP3 inflammasome activity and contribute to AD pathogenesis. In microglia derived from an AD mouse model, we have observed an increased number of MERCS with tighter mitochondria-ER apposition, accompanied by elevated mitochondrial activity. Consistent with this, there are more MERCS in microglia harbouring inflammasome, and inflammasome activation occurs at these sites. Importantly, genetic modulation of MERCS reduces inflammasome activation and inflammatory cytokine release, highlighting microglial MERCS as a potential contributor to AD progression.