A5057678044- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- T-cell and Retrovirus Studies
- NF-κB Signaling Pathways
- interferon and immune responses
- Immune Cell Function and Interaction
- Cutaneous lymphoproliferative disorders research
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Vector-Borne Animal Diseases
- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Animal Disease Management and Epidemiology
- Dialysis and Renal Disease Management
- RNA modifications and cancer
- Gout, Hyperuricemia, Uric Acid
- Phagocytosis and Immune Regulation
- Acute Kidney Injury Research
Fox Chase Cancer Center
2017-2024
Wuhan Polytechnic University
2020-2023
Affiliated Hospital of Hangzhou Normal University
2022
Affiliated Hospital of Zunyi Medical College
2009-2022
Huazhong Agricultural University
2022
National Cancer Institute
2012-2021
National Institutes of Health
2012-2016
Center for Cancer Research
2012-2016
Zunyi Medical University
2013
University of Massachusetts Chan Medical School
2007-2013
While the recognition of microbial infection often occurs at cell surface via Toll-like receptors, cytosol is also under surveillance for products that breach membrane. An important outcome cytosolic induction IFNα and IFNβ, which are critical mediators immunity against both bacteria viruses. Like many intracellular pathogens, a significant fraction transcriptional response to Mycobacterium tuberculosis depends on these type I interferons, but pathways responsible remain elusive. In this...
Abstract Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as “viral mimicry,” has emerged an effective strategy to convert immunologically “cold” tumors into “hot.” Through curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) potent repressor double-stranded (dsRNA) small cell lung cancers (SCLC). Depletion DHX9 induced accumulation dsRNA and triggered tumor-intrinsic immunity. Intriguingly,...
The Rip2 kinase contains a caspase recruitment domain and has been implicated in the activation of transcriptional factor NF-κB downstream Toll-like receptors, Nod-like T cell receptor. Although linked to Nod signaling, how Nod-Rip2 proteins mediate remained unclear. We find required for Nod2-mediated lesser extent mitogen-activated protein activation. demonstrate that IκB kinase-γ become stably polyubiquitinated upon treatment cells with NOD2 ligand, muramyl dipeptide. also requirement...
Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their to an N-glycolylated form through action of N-acetyl muramic acid hydroxylase (NamH). We used a combination bacterial genetics synthetic chemistry investigate whether N-glycolylation alters NOD2-mediated immunity. Upon infecting macrophages with 12 tumor necrosis factor (TNF) α secretion was NOD2...
Significance The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that can only be cured in roughly 40% cases. These malignant cells rely on the NF-κB signaling pathway for survival. Here, we report genetic or pharmacologic interference with bromodomain and extraterminal domain (BET) chromatin proteins reduces activity ABC DLBCL viability. Unexpectedly, mechanism involves inhibition IκB kinase, key cytoplasmic enzyme activates pathway. by...
K63 polyubiquitin chains spatially and temporally link innate immune signaling effectors such that cytokine release can be coordinated. Crohn's disease is a prototypical inflammatory disorder in which this process may faulty as the major disease-associated protein, NOD2 (nucleotide oligomerization domain 2), regulates formation of K63-linked on I kappa kinase (IKK) scaffolding NEMO (NF-kappaB essential modifier). In work, we study these ubiquitin networks to begin understand biochemical...
Pathological activation of the Toll-like receptor signaling adaptor protein MYD88 underlies many autoimmune and inflammatory disease states. In activated B cell-like (ABC) subtype diffuse large cell lymphoma (DLBCL), oncogenic L265P mutation occurs in 29% cases, making it most prevalent activating this malignancy. IRAK4 kinase accounts for almost all biological functions MYD88, highlighting as a therapeutic target diseases driven by aberrant signaling. Using innovative structure-based drug...
AbstractIn multiple tumor types, activation of the transcription factor NF-κB increases resistance cells to anticancer therapies and contributes progression. Genotoxic stress induced by chemotherapy or radiation therapy triggers ATM-dependent translocation essential modifier (NEMO), also designated IκB kinase γ (IKKγ), from nucleus cytosol, resulting in mechanisms not yet fully understood. RIP1 has been implicated this response found be modified with damaged DNA; however, nature modification...
Abstract Regulation of the actin cytoskeleton is crucial for normal development and function immune system, as evidenced by severe abnormalities exhibited patients bearing inactivating mutations in Wiskott–Aldrich syndrome protein (WASP), a key regulator dynamics. WASP exerts its effects on dynamics through multisubunit complex termed Arp2/3. Despite critical role played Arp2/3 an effector WASP-mediated control over polymerization, components had not previously been identified cause...
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival cells. As single agent, CDK6 inhibitor palbociclib induced cell cycle arrest apoptosis in models wild-type TP53. had inactivated TP53 genetically were relatively resistant to owing compensatory CDK2...
Elotuzumab (Elo) is an IgG1 monoclonal antibody targeting SLAMF7 (CS1, CRACC, and CD319), which highly expressed on multiple myeloma (MM) cells, natural killer (NK) subsets of other leukocytes. By engaging with FcγRIIIA (CD16), Elo promotes potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) macrophage-mediated phagocytosis (ADCP) toward SLAMF7+ MM tumor cells. Relapsed/refractory patients treated the combination Elo, lenalidomide, dexamethasone have improved...
Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity hallmark ATLL pathogenesis. However, mechanisms by which cells evade natural killer (NK)-cell-mediated have been poorly understood. Here we show CD48 expression in determines sensitivity for NK-cell-mediated cytotoxicity against cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic...
NOD1 and NOD2 are members of the NOD-like receptor family cytosolic pattern recognition receptors that recognize specific fragments bacterial cell wall component peptidoglycan. Neisseria species unique amongst Gram-negative bacteria in they turn over large amounts peptidoglycan during growth. We examined ability to gonorrhoeae, determined role NOD-dependent signaling regulating immune response gonococcal infection. Gonococci, as well conditioned medium from mid-logarithmic phase grown...
Abstract Purpose: For patients with refractory/relapsed Hodgkin lymphoma (roughly 20% of total cases), few effective therapeutic options exist. Currently, brentuximab vedotin (BV), a drug-conjugated anti-CD30 antibody, is one the most approved therapy agents for these patients. However, many do not achieve complete remission and ultimately develop BV-resistant disease, necessitating more detailed understanding molecular circuitry that drives BV sensitivity mechanism resistance. Experimental...