Chi Lab
Principal Investigator: Jen-Tsan Ashley Chi
Institution: Duke University (Durham, NC)
Primary Subfield: Immunology
Recruitment Status: ✅ Hiring Postdocs
Research Focus
Project Abstract Proper recognition and disposal of aberrant RNA is essential for maintaining immune tolerance while enabling appropriate antiviral defense. This process is tightly regulated by RNA decay enzymes such as the 5′→3′ exonuclease XRN1, whose activity prevents the accumulation of immunostimulatory RNA species that can aberrantly activate RNA-sensing pathways like RIG-I and MDA5. Recent findings have uncovered an unexpected role for the cytosolic enzyme MESH1 in regulating nucleotide metabolism and immune responses to RNA. Originally identified as a metazoan homolog of the bacterial SpoT, MESH1 has been shown by us to degrade NADPH and promote ferroptosis. Our preliminary data now identify 3′-phosphoadenosine 5′- phosphate (PAP) as a novel, physiologically relevant substrate for MESH1. Furthermore, MESH1-deficient macrophages exhibit an exaggerated response to immunostimulatory RNA. One probable explanation is that PAP, a byproduct of cellular sulfation reactions, inhibits the XRN1, leading to the accumulation of immunostimulatory RNAs that aberrantly trigger antiviral signaling. We hypothesize that MESH1 is a critical PAP phosphatase that protects cells from PAP-induced…
Active NIH Awards
- 1R21AI200131-01: MESH1 Regulates RNA Sensing Through Nucleotide Metabolism (2026)
- 1R21CA297690-01A1: Noncovalent interaction of mutant KRAS inhibitors (2025)
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