Research
We investigate how lipid homeostasis and protein lipidation shape the organization and function of cellular membranes in health and disease. Pathogens exploit Host membranes for replication and spread, while host cells detect and counteract such perturbations. By dissecting these molecular interactions, we uncover fundamental principles of membrane biology and their impact on infection, immunity, and therapeutic opportunities.
Our lab combines biochemical assays, structural analysis (e.g., cryo-ET), advanced imaging, and quantitative proteomics/lipidomics across diverse infection models, with a focus on SARS-CoV-2. A central theme to our research is protein S-acylation—the reversible attachment of fatty acids to proteins—which regulates membrane dynamics across biology and plays a central role in human health and disease (see our review below).
From this perspective, we explore different questions:
How does S-acylation of viral proteins shape viral membranes and influence replication?
How is host lipidation remodeled during infection, and what are the consequences for immunity?
How do host cells sense membrane lipid damage and translate it into innate immune defense?
Viral protein lipidation
We showed that S-acylation of viral proteins, particularly the Spike glycoprotein, alters viral composition and boosts infectivity. This opens fundamental questions on how lipidation controls viral envelopes, and broader host–virus interactions. We are now expanding this work to other viral and host proteins to uncover principles of membrane remodeling during infection.
Host lipidation
We mapped how host lipidation is rewired during infection (volcano plot - manuscript in preparation) and found that blocking depalmitoylation enzymes can inhibit SARS-CoV-2 infection. The next step is to detail the main host proteins involved, define their roles in infection and immunity, and explore how lipidation integrates with innate immune regulation. Our lab is now focusing on key targets to uncover how these processes shape immunity and disease.
Lipid oxidation damage & innate immunity
We discovered that ZDHHC20, a major acyltransferase that modifies viral proteins from pathogens such as SARS, HIV, and influenza, is transcriptionally regulated during infection. SARS-CoV-2 hijacks this regulation to maintain its lipid composition and infectivity. This study uncovered a novel regulatory layer of protein S-acylation, also engaged during bacterial toxin damage and colitis in vivo. In our most recent preprint, we describe the lipid oxidative radical damage (LORD) pathway, which links lipid ROS stress to innate immunity (manuscript under review). The LORD pathway reveals new regulators and effectors critical for overcoming oxidative stress and infection, raising the question of how these processes are tuned by protein acylation. We are continuing to explore this with collaborators, investigating its implications across infection, inflammation, and redox biology.
