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High-quality basic & translational research representative of biomedical specialties & physician-scientists. Bluesky: https://nitter.cf/t.co/AksMLnEAMq

Joined October 2016
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Immune cell profiling from pleural fluid offers prognostic value and potential targets in lung cancer: doi.org/10.1172/jci.insight.… This issue’s Cover features work by Khatri et al., reporting that macrophage reprogramming is associated with poor survival outcomes for patients with metastasis of #LungCancer to the pleural space. The cover image shows tumor-associated macrophages (CD163, red) surrounding an invading lung cancer metastatic lesion (pan-cytokeratin, green). Credit: Aaditya Khatri. @DukePACC @DukePulmFellows @CHESTFoundation
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Research Spotlight💫: A promising targeted therapy approach to overcome OXPHOS-dependent resistance in acute myeloid leukemia (AML): doi.org/10.1172/jci.insight.… Goutham Narla @gouthamnarla & team @UMich report on a new PP2A-B56α-based strategy that overcomes treatment resistance in preclinical AML models by targeting cell metabolism. Mechanistically, stabilization of the PP2A-B56α complex overcomes venetoclax-azacitidine resistance by impairing OXPHOS. #AML @the_asci
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Halloween Highlight💫 : The ghoulish figure in this full spectrum flow cytometry and mass cytometry plot embodies how fibrosis-associated endothelial cells turn nasty during #LiverDisease: doi.org/10.1172/jci.insight.… Mapping vascular plasticity during fibrogenesis identifies fibrosis-associated endothelial cells in early-stage liver disease by Gkantsinikoudi et al.: The plot was generated by overlaying the different treatment groups with the 4 different clusters of expanded fibrosis associated endothelial cells (FAEC).
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Dufton and colleagues spotted another eerie connection in their work. They named this image A Scarry Night after its resemblance to a Starry Night by Van Gogh as well as its nexus with scar tissue. It shows the stages of endothelial-to-mesenchymal transition (EndMT) of healthy liver EC (blue) as they express increasing amounts of TAGLN (red) going counterclockwise.
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The first mouse safety study of #Ebola vaccine in pregnancy finds it largely safe, but early vaccination can increase fetal loss via interferon signaling: doi.org/10.1172/jci.insight.… Sandra M. Blois @Blois_Lab & team established a pregnant mouse model for investigating the effects of VSV-EBOV vaccination on pregnancy outcomes and fetal development. Vaccination at various gestation revealed early timepoints raised pregnancy loss. #Vaccines
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Dorina Avram @dorina_avram & team @MoffittNews initially observed reduced levels of the E3 ubiquitin ligase HECTD3 in colon samples from patients with ulcerative colitis: doi.org/10.1172/jci.insight.… Using a murine colitis model, the researchers reveal how HECTD3 controls immune colonic inflammation and protects against colitis by restricting MyD88 activation and signaling. @gur_ola @mariola_ferraro @gatechatl #colitis
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Interesting new paper in JCI Insight “Deep learning–based histologic classifiers enable molecular subtyping of metastatic prostate cancer” by Dr. Juan Miguel Mosquera & colleagues @JCI_insight @juanmiguel12148 #Pathology #PathX #PathTwitter #LabMedicine doi.org/10.1172/jci.insight.…
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A new, orally bioavailable DYRK1A inhibitor Leucettinib-92 LCTB-92 as a first-in-class therapy for treating myocardial infarction in a preclinical animal model: doi.org/10.1172/jci.insight.… Matthew J. Wolf @MattWolfMDPhD & team @UVA find Inhibition of DYRK1A using LCTB-92 induces cardiomyocyte proliferation and improves heart function in a mouse model of ischemic/reperfusion injury. The team developed a computational network model to predict experimental outcomes then validated the predictions using selective DYRK1A inhibitors. The images show circled regions with GFP+ cardiomyocytes, indicating cell cycle re-entry after ischemia/reperfusion myocardial infarction. #HeartAttack @the_asci
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Network Modeling Predicts How DYRK1A Inhibition Promotes Cardiomyocyte Cycling after Ischemic/Reperfusion Injury: doi.org/10.1172/jci.insight.…
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JCI insight retweeted
ASCI member Goutham Narla @gouthamnarla & colleagues just published a new paper @JCI_insight (doi.org/10.1172/jci.insight.…)! In this glimpse Behind the Paper, (1/4) Dr. Narla & Dr. O'Connor discuss results; (2/4) Dr. Romero-Murillo & Dr. Peris count CD34+ colonies; (3/4) Dr. Romero-Murillo shares the results during her PhD defense; and (4/4) Dr. Romero-Murillo, Nerea Marcotegui, Dr. Odero, Dr. Vicente, and Dr. Peris (left-to-right) say hello from Dr. Odero's laboratory. 🧵
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A promising targeted therapy approach to overcome OXPHOS-dependent resistance in acute myeloid leukemia (AML): doi.org/10.1172/jci.insight.… Goutham Narla @gouthamnarla & team @UMich report on a new PP2A-B56α-based strategy that overcomes treatment resistance in preclinical AML models by targeting cell metabolism. Mechanistically, stabilization of the PP2A-B56α complex overcomes venetoclax-azacitidine resistance by impairing OXPHOS. #AML @the_asci
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But please check our our paper - there's a lot more in there for helping Castleman Disease patients to be diagnosed in a more timely way and to help others who share our passion for the overlooked roles of lymph node stromal cells in human disease! insight.jci.org/articles/vie…
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Wanted to share our years-long effort to understand the role of lymph node stromal cells in Castleman! One of the biggest repositories of human lymph node stromal cell data. insight.jci.org/articles/vie… @DavidFajgenbaum @CureCastleman @Stromal_Immunol @PennMedCSO @JCI_insight
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JCI insight retweeted
More future physician-scientists are applying for their first NIH grant, and fewer are getting awarded. Our national survey of 256 trainees found what holds them back and what helps insight.jci.org/articles/vie… @Bthomas_ZOU @_CynthiaTang @DaveArnoldLab
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Another collaborative work this month-collab with Avram lab: JCI Insight "The E3 ubiquitin ligase HECTD3 controls immune colonic inflammation by restricting Myd88 activation and signaling " insight.jci.org/articles/vie…
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What if Mycobacterium tuberculosis couldn’t evade macrophage defenses? Campos et al. @UTSWMedCenter identify SMURF2 as a conserved negative regulator of selective autophagy that suppresses macrophage control of M. tuberculosis: doi.org/10.1172/jci.insight.… The figure shows increased phagosomal association in human macrophages exposed to the SMURF2 inhibitor Heclin. @the_asci #tuberculosis
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🧬 Excited to share our new study in @JCI_Insight! We show that stabilizing PP2A-B56α can overcome venetoclax–azacitidine resistance in acute myeloid leukemia by targeting mitochondrial metabolism.
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Sunday Read💫: A novel axis that can fine-tune the immune response to glomerular and tubule cell damage: doi.org/10.1172/jci.insight.… Jamie R. Privratsky @JamiePrivratsky & team @DukeKidney @Duke_Anesthesia identify a novel myeloid cell-endothelial cell immunoregulatory axis, supporting a model whereby myeloid IL-1R1 activity constrains ER stress–mediated EBI3/IL27 secretion, thereby attenuating type I IFN expression in kidney endothelial cells and ameliorating autoimmune nephritis. The figure shows anti-IFNAR1 therapy abrogates kidney injury after NTS nephritis in mice lacking IL-1R1 specifically in myeloid cells (bottom); littermate controls (top). #AKI #Nephrology #kidney #macrophage
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Saturday Highlight💫: Full-length macrophage TREM2 protects against atherosclerosis: doi.org/10.1172/jci.insight.… Tang et al. unravel the links between #Prediabetes, #CardiovascularDisease, and #HepaticSeatosis, identifying increased levels of soluble TREM2 in human subjects and preclinical models of prediabetes. Soluble, macrophage-derived TREM2 associated with plasma apolipoprotein C3, which in turn reduces clearance of triglyceride-rich lipoproteins and increases heart disease risk. Importantly, preservation of full length TREM2 in prediabetic, steatotic mice reduced dyslipidemia and atherosclerosis.
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This study links faulty DNA repair to abnormal immune responses: doi.org/10.1172/jci.insight.… Yusuke Yamashita & team discover a partial defect in DNA repair weakens immune defenses yet promotes severe intestinal inflammation in a novel mouse model that recapitulates DNA-LIG4 syndrome. #DNARepair #Immunodeficiency #IntestinalInflammation
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Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival: doi.org/10.1172/jci.insight.…
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