Ling Qi, PhD
The National Institute on Aging awarded a prestigious $4.1 million R01 grant to a pioneering, multi-principal investigator team led by Ling Qi, PhD, professor and chair of the Department of Molecular Physiology and Biological Physics at the University of Virginia and Zhen Zhao, PhD, of the University of Southern California
The grant, titled “ERAD-STING Crosstalk in Microglia: Unraveling the Pathogenesis of Alzheimer’s Disease,” will fund innovative research into the complex mechanisms driving Alzheimer’s disease (AD), the most common form of dementia.
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, largely driven by amyloid- and Tau-mediated proteinopathies. However, emerging research suggests that AD pathogenesis is influenced by additional factors at genetic, molecular, and cellular levels. This study aims to elucidate the role of innate immunity and its novel regulatory mechanisms in neuroinflammation associated with AD.
Dr. Qi’s and Dr. Zhao’s laboratories will jointly investigate how the STING pathway, an integral component of the innate immune system, interacts with the endoplasmic reticulum-associated degradation (ERAD) system in AD. The Qi lab has spent over 15 years exploring the SEL1L-HRD1 ERAD complex, crucial for managing misfolded ER proteins, while the Zhao lab has focused on innate immunity’s role in neurodegeneration and AD over the past decade.
Recent independent findings from both labs underscore the significance of the ERAD-STING axis in AD. Dr. Qi’s lab reported that STING is regulated by ERAD in macrophages (Qi et al., Nat Cell Biol 2023), and Dr. Zhao’s lab found that STING activation in microglia drives neuroinflammation and AD pathogenesis (Zhao et al., Nat Aging 2023).
By combining their expertise in cell biology, immunology, and neurobiology, the researchers seek to establish the cGAS-STING pathway as a critical link between innate immunity and Alzheimer’s disease. Their research will explore how the SEL1L-HRD1 ERAD complex regulates STING-mediated neuroinflammation and its implications for aging and AD progression.
This collaborative effort promises to advance our understanding of Alzheimer’s disease and identify potential therapeutic targets for this devastating condition. The team is excited about the potential impact of their research and looks forward to sharing their findings with the scientific community and beyond.
Filed Under: Research