Author: Sheryl Rosen

Jianbin Ruan Paper Accepted for Publication in Nature

In this paper, Gasdermin D pore structure reveals preferential release of mature interleukin-1, Ruan and collaborators reported the cryo-EM structure of human Gasdermin D (GSDMD) pore, an inflammatory cell death executioner molecule, at 3.9 Å resolution. GSDMD pore exhibits large differences in symmetry and dimensions from the previously reported GSDMA3, a mouse homolog. Beyond the structure of the human GSDMD pore, the paper also demonstrated that GSDMD forms an acidic shield that directly regulates IL-1 secretion via a charge-based mechanism. This discovery will facilitate future investigation into the GSDMD secretome and, to our knowledge, first proposes how large transmembrane pores may achieve substrate selectivity. This study is a collaborative effort between Dr. Ruan’s lab and the laboratories of Wu and Lieberman at Harvard Medical School, the laboratory of Greka at Broad Institute of MIT, and the laboratory of Jacobson at the University of California San Francisco.

Jianbin Ruan, Ph.D.

Vijay Rathinam Paper Accepted in Nature Immunology

In an article entitled “Intracellular immune sensing promotes inflammation via gasdermin D-driven release of a lectin alarmin” published in Nature Immunology, Dr. Vijay Rathinam’s lab discovered a sugar-binding protein called galectin-1 as bona fide danger molecule that is released during excessive cell death promoting "cytokine storm" and inflammation during sepsis. The findings from the study advances our understanding of pathogenic mechanisms in sepsis, the leading cause of death for patients in the intensive care unit with 270,000 deaths annually in the US. and lay the foundation for identifying novel biomarkers and therapeutic targets in sepsis. This study was led by Dr. Ashley Russo, a previous graduate student in the Rathinam lab and involved key collaborations with the laboratories of Vella, Menoret, Zhou, Ruan, and Vanaja in the Department of Immunology as well as additional labs in University of Florida, Jena University Hospital, Germany and the Experimental Medicine and Biology Institute, University of Buenos Aires, Argentina.

Dr. Vijay Rathinam standing next to Ashley Russo

Sivapriya Kailasan Vanaja Paper Accepted in Science Immunology

Congratulations to Dr. Sivapriya Kailasan Vanaja for having a paper from her lab, Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS, accepted for publication in Science Immunology. The paper first authored by Morena Mendonca, a postdoctoral fellow in the Kailasan Vanaja lab, demonstrates that Shiga toxin, a primary virulence factor of Enterohemorrhagic Escherichia coli, suppresses cytosolic LPS-mediated inflammasome responses by inhibiting the cleavage of gasdermin D. The findings from this study provide insights into the mechanisms by which bacterial pathogens modulate the host innate immune responses to successfully establish an infection.

Sivapriya Kailasan Vanaja, Ph.D., D.V.M.