Zhu Lab
Principal Investigator: Shiwei Zhu
Institution: Case Western Reserve University (Cleveland, OH)
Primary Subfield: Immunology
Recruitment Status: ✅ Hiring Postdocs
Research Focus
Project Abstract Intracellular bacterial pathogens cause significant morbidity and mortality worldwide, with antibiotic resistance necessitating alternative therapeutic approaches. The interferon- induced GTPase GBP1 serves as a critical mediator of cell-autonomous immunity by forming antimicrobial coats on diverse pathogens including Salmonella, Mycobacterium, and Toxoplasma. Despite two decades since the first GBP1 X-ray structure was solved, it lacks physiological relevance, leaving GBP1-mediated immune defense mechanisms unknown. How does prenylation switch GBP1 function? How does GBP1 recognize diverse pathogens? How does it discriminate pathogen from host membranes? Our preliminary data show farnesylation is essential for coat formation, Kdo2-lipid A is the minimal LPS recognition unit, and GBP1 forms ring-like polymers as intermediates. We hypothesize prenylation switches GBP1 to function as a pattern recognition receptor employing conserved conformations to recognize diverse pathogen surfaces while discriminating self-membranes. Aim 1 will define how prenylation drives antimicrobial activity by comparing farnesylation versus geranylgeranylation and determining cryo-EM struc…
Active NIH Awards
- 1R01AI201547-01: Dissecting GBP1-Mediated Immune Responses: From Pathogen Sensing and Defense to Organelle Dynamics (2026)
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