The Wu Lab
The Wu laboratory of mechanistic immunology focuses on elucidating cellular and structural regulation in innate immune pathways, in particular the inflammasome pathway.
Congratulations to Mila for her recent Cell paper, "NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation".
December 2021 | PDF |
"The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Continue Reading
Congratulations to Chen for his recent Cell paper, "Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome".
October 2021 | PDF |
"NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here, we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with double-stranded RNA (dsRNA) in vitro and in cells, and an intrinsically disordered poly-lysine sequence (K350-354) of NLRP6 is important for multivalent interactions, phase separation, Continue Reading
Congratulations to Bobby for successfully defending his PhD dissertation.
Congratulations to Shiyu for successfully defending his PhD dissertation.
August 2021 |
Congratulations to Shiyu for his recent Nature paper, "Gasdermin D pore structure reveals preferential release of mature interleukin-1"
May 2021 | PDF |
"As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as IL-1β and IL-18. Cleaved GSDMD forms transmembrane pores to enable the release of IL-1 and to drive cell lysis through pyroptosis1-9. Here we report cryo-electron microscopy structures of the pore and the prepore of GSDMD. Continue Reading
Congratulations to Hao, who has been elected to The American Academy of Arts & Sciences (AAAS) for the year of 2021.
April 2021 |
"Academy President David W. Oxtoby and Chair of the Board of Directors Nancy C. Andrews have announced that more than 250 outstanding individuals have been elected to the Academy in 2021. The new members are listed below, starting with a complete list in alphabetical order followed by members organized by area and specialty. International Honorary Members are indicated with (IHM) after their names. Information about members elected in prior years is in our member directory. "Continue Reading
Congratulations to Bobby and Humayun for their recent Nature paper, "DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation"
April 2021 | PDF |
"Nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 1 (NLRP1) is an infammasome sensor that mediates the activation of caspase-1 to induce cytokine maturation and pyroptosis . Gain-of-function mutations of NLRP1 cause severe infammatory diseases of the skin. NLRP1 contains a function-to-fnd domain that auto-proteolyses into noncovalently associated subdomains, and proteasomal degradation of the repressive N-terminal fragment of NLRP1 releases its infammatory C-terminal fragment (NLRP1 CT)." Continue Reading
Congratulations to Venkat and Roberto for their recent Science paper, "HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation"
September 2020 | PDF |
"Inflammasomes are supramolecular complexes that play key roles in immune surveillance. This is accomplished by the activation of inflammatory caspases, which leads to the proteolytic maturation of interleukin 1β (IL-1β) and pyroptosis. Here, we show that nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containg protein 3 (NLRP3)- and pyrin-mediated inflammasome assembly, caspase activation, and IL-1β conversion occur at the microtuble-organizing center (MTOC)." Continue Reading
Congratulations to Jacob and Shiyu for their recent Nature Immunology paper, "FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation"
"Inflammation is the alarm system by which cells first respond to potential danger, but in excess, inflammation can be fatal. In COVID-19, for example, overactive inflammation has led to severe complications and even death for many hospitalized patients. Research in mice led by Harvard Medical School and Boston Children’s Hospital now reveals that the FDA-approved drug disulfiram, commonly used for treating alcoholism, blocks a key gatekeeper protein involved in inflammation." Continue reading
Congratulations to Humayun, Li, and Weili for their recent Nature paper, "Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome"
"The NLRP3 inflammasome can be activated by stimuli that include nigericin, uric acid crystals, amyloid-β fibrils and extracellular ATP. The mitotic kinase NEK7 licenses the assembly and activation of the NLRP3 inflammasome in interphase. Here we report a cryo-electron microscopy structure of inactive human NLRP3 in complex with NEK7, at a resolution of 3.8 Å. The earring-shaped NLRP3 consists of curved leucine-rich-repeat and globular NACHT domains..." Continue reading
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