The Wu Lab
The Wu laboratory of structural and mechanistic immunology focuses on elucidating cellular and structural regulation in innate immune pathways, in particular the inflammasome pathway.
Congratulations to Hao who wins the AAI-Thermo Fisher Meritorious Career Award.
June 2022 | PDF |
"Inflammasomes are cytosolic innate immune complexes that activate caspase-1 upon detection of pathogenic and endogenous dangers1-5, and NLRP3 is an inflammasome sensor of membrane damage highly important in inducing inflammation2,6,7. Here we report cryo-EM structures of disk-shaped active NLRP3 oligomers in complex with ATP𝛾S, the centrosomal kinase NEK7, and the adaptor protein ASC which recruits caspase-1. " Continue reading
Congratulations to Le for his recent Nature paper, "Cryo-EM structures of the active NLRP3 inflammasome disk.
Congratulations to Ying and Xiong for their recent Nature paper, " Structural principles of B cell antigen receptor assembly"
December 2022 | PDF |
"The B cell antigen receptor (BCR) is composed of a membrane-bound class M, D, G, E or A immunoglobulin for antigen recognition1-3 and a disulfide-linked Igα (also known as CD79A) and Igβ (also known as CD79B) heterodimer (Igα/β) that functions as the signalling entity through intracellular immunoreceptor tyrosine-based activation motifs (ITAMs)4,5. The organizing principle of the BCR remains unknown. Here we report cryo-electron microscopy structures of mouse full-length IgM BCR and its Fab-deleted form.." Continue reading
Congratulations to Dr. Xiong Pi for being awarded the Cancer Research Institute (CRI) Irvington Postdoctoral
Congratulations to Hao who received the 2022 William B. Coley Award for Distinguished Research in
Basic and Tumor Immunology.
Congratulations to Dr. Ying Dong who has been awarded a 2-year postdoctoral fellowship from the Charles A. King Trust.
Congratulations to Dr. Caitlin Walker who was awarded an NIH F32 Ruth L. Kirschstein Postdoctoral NRSA Fellowship through NIGMS.
Congratulations to Dr. Venkat Magupalli for being promoted to assistant professor of Boston Children's Hospital Pediatrics.
Congratulations to Dr. Yumei Zheng for being awarded a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund.
Congratulations to Dr. Le Xiao, who has been awarded a 2-year Ben J. Lipps Research Fellowship Program from The American Society of Nephrology.
Congratulations to Dr. Mohammad Kawsar Manik for being awarded the Cancer Research Institute (CRI) Irvington Postdoctoral Fellowship.
Congratulations to Dr. Caitlin Walker who was awarded the NIH T32 Pathophysiology of Human Blood Cells
Congratulations to Pietro, Ying and Xiong for their recent Science paper "Structure of cytoplasmic ring of nuclear pore complex by integrative cryo-EM and AlphaFold".
June 2022 | PDF |
"The nuclear pore complex (NPC) is the molecular conduit in the nuclear membrane of eukaryotic cells that regulates import and export of biomolecules between the nucleus and the cytosol, with vertebrate NPCs ~110 to 125 MDa in molecular mass and ~120 nm in diameter. NPCs are organized into four main rings: the cytoplasmic ring (CR) at the cytosolic side, the inner ring and the luminal ring on the plane of the nuclear membrane, and the nuclear ring facing the nucleus.." Continue reading
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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