A5012943946- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Bacteriophages and microbial interactions
- interferon and immune responses
- Immune Cell Function and Interaction
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Lung Cancer Research Studies
- Neuroblastoma Research and Treatments
- SARS-CoV-2 and COVID-19 Research
- Advanced Biosensing Techniques and Applications
- Systemic Sclerosis and Related Diseases
- Cytokine Signaling Pathways and Interactions
- vaccines and immunoinformatics approaches
- CAR-T cell therapy research
- Immune Response and Inflammation
- Cancer-related molecular mechanisms research
- Mast cells and histamine
- Dermatological and Skeletal Disorders
- Dermatologic Treatments and Research
- RNA regulation and disease
- NF-κB Signaling Pathways
- Tryptophan and brain disorders
Dana-Farber Cancer Institute
2019-2022
Dartmouth College
2020
Abstract Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of uniquely upregulates MHC I, enriching for ICB benefit. In vitro modeling confirms epigenetic recovery I in following loss neuroendocrine differentiation, tracks with derepression STING. Transient EZH2 inhibition expands these nonneuroendocrine...
Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of disease. However, aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive remains largely refractory to current immunotherapeutic approaches. The stimulator interferon genes (STING) DNA sensing pathway emerged as next-generation immunotherapy target potent local immune stimulatory properties. Here, we investigated status STING GBM...
Activation of the stimulator interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding mechanism action in human tumors is key developing therapeutic combinations that activate effective innate immunity. Here, we report malignant pleural mesothelioma cells robustly express and are responsive agonist treatment ex vivo. Using dynamic single-cell RNA sequencing explants treated with a agonist, observed CXCR3...
Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation SSc. We undertook this study characterize the profile SSc monocyte-derived and assessed their interaction with fibroblasts.Plasma peripheral blood mononuclear (PBMCs) were obtained from whole patients (n = 24) age- sex-matched healthy controls 12). Monocytes cultured autologous or allogeneic plasma...
Abstract Triple-negative breast cancer (TNBC) is a heterogeneous disease enriched for mutations in PTEN and dysregulation of innate immune signaling. Here, we demonstrate that Rab7, recently identified substrate phosphatase activity, also the signaling kinases TANK-binding kinase 1 (TBK1)/IκB ϵ (IKKϵ) on same serine-72 (S72) site. An unbiased search novel TBK1/IKKϵ substrates using stable isotope labeling with amino acids cell culture phosphoproteomic analysis Rab7-S72 as top hit. PTEN-null...
Intratumoral recruitment of immune cells following innate activation is critical for anti-tumor immunity and involves cytosolic dsDNA sensing by the cGAS/STING pathway. We have previously shown that KRAS-LKB1 (KL) mutant lung cancer, which resistant to PD-1 blockade, exhibits silencing STING, impaired tumor cell production chemoattractants, T exclusion. Since vasculature also a gatekeeper infiltration into tumors, we developed novel microfluidic model study KL tumor-vascular interactions....
Abstract Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of disease. However, aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive remains largely refractory to current immunotherapeutic approaches. The cGAS-STING cytoplasmic double stranded DNA (dsDNA) sensing pathway emerged as next-generation immunotherapy target potent local immune stimulatory properties. Here, we...
<div>Abstract<p>Activation of the stimulator interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding mechanism action in human tumors is key developing therapeutic combinations that activate effective innate immunity. Here, we report malignant pleural mesothelioma cells robustly express and are responsive agonist treatment <i>ex vivo</i>. Using dynamic single-cell RNA sequencing...
Abstract Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in Systemic sclerosis (SSc), and we have shown that constitute the dominant inflammatory signature SSc tissue. However, little is known about how these cells contribute to fibrotic activation SSc. Using a bioinformatics approach, show profile blood-derived human significantly enriched patient skin. We characterize immunophenotype pro-fibrotic, demonstrating are activated under basal conditions,...
<div>Abstract<p>Triple-negative breast cancer (TNBC) is a heterogeneous disease enriched for mutations in PTEN and dysregulation of innate immune signaling. Here, we demonstrate that Rab7, recently identified substrate phosphatase activity, also the signaling kinases TANK-binding kinase 1 (TBK1)/IκB ϵ (IKKϵ) on same serine-72 (S72) site. An unbiased search novel TBK1/IKKϵ substrates using stable isotope labeling with amino acids cell culture phosphoproteomic analysis Rab7-S72 as...
<p>SF1: Unaltered immunoblots for Fig 4E. SF2: 4F. SF3: 4G. SF4: Additional phosphopeptide analysis cell based and in vitro SILAC screen. SF5: Lower magnification (40X) of basal expression V5 Rab7 mutants, to correspond with 4A. SF6: EGFR STING localization following TBK1/IKKE inhibition. SF7: Schematic Rab7S72 role regulating STING/TBK1/IKKE signaling TNBCs. STableS3: Primer sequence qRT-PCR. STableS4: List antibodies. STableS5: PTEN/STING Staining a TNBC TMA.</p>
<p>SF1: Unaltered immunoblots for Fig 4E. SF2: 4F. SF3: 4G. SF4: Additional phosphopeptide analysis cell based and in vitro SILAC screen. SF5: Lower magnification (40X) of basal expression V5 Rab7 mutants, to correspond with 4A. SF6: EGFR STING localization following TBK1/IKKE inhibition. SF7: Schematic Rab7S72 role regulating STING/TBK1/IKKE signaling TNBCs. STableS3: Primer sequence qRT-PCR. STableS4: List antibodies. STableS5: PTEN/STING Staining a TNBC TMA.</p>
<div>Abstract<p>Activation of the stimulator interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding mechanism action in human tumors is key developing therapeutic combinations that activate effective innate immunity. Here, we report malignant pleural mesothelioma cells robustly express and are responsive agonist treatment <i>ex vivo</i>. Using dynamic single-cell RNA sequencing...
<div>Abstract<p>Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of uniquely upregulates MHC I, enriching for ICB benefit. <i>In vitro</i> modeling confirms epigenetic recovery I in following loss neuroendocrine differentiation, tracks with derepression STING. Transient EZH2...
<div>Abstract<p>Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of uniquely upregulates MHC I, enriching for ICB benefit. <i>In vitro</i> modeling confirms epigenetic recovery I in following loss neuroendocrine differentiation, tracks with derepression STING. Transient EZH2...
<p>Supplementary Figures 1-12</p>