TWINCORE Seminar - Systems Immunology
Dr. Verónica Durán
Stanford University School of Medicine, Stanford
"Age-dependent immune landscape in dengue infection and disease progression"
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Prof. Shirit Einav
Stanford University School of Medicine, Stanford
"Targeting an understudied lipid kinase to restore lysosomal function in viral infection and neurodegeneration"
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- TWINCORE Seminar Room 0020
Speakers:
Dr. Verónica Durán
Stanford University School of Medicine, Stanford
Prof. Shirit Einav
Stanford University School of Medicine, Stanford
Abstracts:
Dr. Veronica Durán
Age-dependent immune landscape in dengue infection and disease progression
Dengue lacks approved treatments and shows unpredictable outcomes due to unclear immune determinants. Using systems immunology, integrating single-cell transcriptomics, functional experiments, and plasma proteomics, we investigate how age influences immune responses during acute infection in individuals who resolve or develop severe dengue. We identify age-dependent differences in interferon, NF-κB, antigen presentation, and regulatory pathways, revealing that immune setpoints across the lifespan determine disease trajectories.
Prof. Shirit Einav
Targeting an understudied lipid kinase to restore lysosomal function in viral infection and neurodegeneration
We identified the lipid kinase PIP4K2C as a negative regulator of lysosomal function. Its inhibition restores lysosomal acidification and proteolysis via phosphoinositide remodeling on lysosomal membranes and TFEB activation. We discovered that viruses like SARS-CoV-2 bind PIP4K2C to arrest autophagic flux and evade their own degradation, and that inhibiting it exerts broad antiviral activity. Applying this strategy to neurodegeneration, we found that targeting PIP4K2C also rescues key phenotypes of Amyotrophic lateral sclerosis and Parkinson’s disease. These results uncover new mechanisms of lysosomal regulation and establish PIP4K2C as a druggable target for lysosomal restoration across pathologies.
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