Project Grant R21AI202554

The National Institute of Allergy and Infectious Diseases, a component of the Department of Health and Human Services National Institutes of Health, awarded $267,000 to The Children's Hospital Corporation (doing business as Boston Children's Hospital) on August 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855).

The award funds research decoding gasdermin D (GSDMD) pore clustering as a regulatory checkpoint controlling pyroptosis, a lytic and inflammatory form of programmed cell death. The research will elucidate the organization and molecular basis of clustered GSDMD pores and define their functional role in controlling lytic cell death. The investigator hypothesizes that GSDMD palmitoylation drives formation of higher-order clustered pores on the plasma membrane, serving as a critical checkpoint that controls the transition from non-lytic cytokine release to membrane rupture during pyroptosis. Work will employ cryo-electron tomography, super-resolution DNA-PAINT, and single-molecule TIRF microscopy to define the organization and molecular mechanisms underlying GSDMD cluster-pore formation and to determine the functional significance of pore clustering. Understanding this molecular switch is intended to support development of strategies to modulate inflammation and cell death in sepsis, autoimmune diseases, and cancer.

Performance is located in Boston, Massachusetts, with an ultimate completion date of June 30, 2028. This is a project grant, classified as an assistance award to a nonprofit research institution.