JCI insight @JCI_insight

@MattWolfMDPhD @UVA Network Modeling Predicts How DYRK1A Inhibition Promotes Cardiomyocyte Cycling after Ischemic/Reperfusion Injury: doi.org/10.1172/jci.in…

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.in… 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

ASCI member Goutham Narla @gouthamnarla & colleagues just published a new paper @JCI_insight (doi.org/10.1172/jci.in…)! 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.in… 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

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/view/…

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/view/… @DavidFajgenbaum @CureCastleman @Stromal_Immunol @PennMedCSO @JCI_insight

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/view/… @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/view/…

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.in… The figure shows increased phagosomal association in human macrophages exposed to the SMURF2 inhibitor Heclin. @the_asci #tuberculosis

🧬 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.

Sunday Read💫: A novel axis that can fine-tune the immune response to glomerular and tubule cell damage: doi.org/10.1172/jci.in… 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.in… 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.in… 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

Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival: doi.org/10.1172/jci.in…

Immune cell profiling from pleural fluid offers prognostic value and potential targets in lung cancer: doi.org/10.1172/jci.in… 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

Why does tuberculosis infection worsen HIV-1 outcomes? doi.org/10.1172/jci.in… Samantha Cronin, Gabriel Duette @_GabrielDuette et al. @WestmeadInst demonstrate that the TB-altered immune microenvironment enriches the presence of genetically intact virus and impairs CD8 T cell-mediated antiviral responses. These results may explain worsened outcomes for people coinfected with HIV-1 and TB. The accompanying image shows the experimental design to evaluate the effect of coculture of pleural effusions from patients with TB and CD8 T cells from people living with HIV. @_GabrielDuette #HIV #TB

An unexpected regulatory relationship reveals a therapeutic vulnerability in high-Wnt tumors: doi.org/10.1172/jci.in… Using pancreatic cancer models, David M. Virshup, Babita Madan & team @dukenus find that the cell-surface receptor EPHA2 cooperates with Wnt in the tumor environment to inhibit MAPK signaling. #CancerBiology #WntSignaling

Really proud of our stellar postdoc @SElasoru 🔥🔥for the Herculean effort to get his "side" project published. Kudos to the stellar study team including but not limited to Zhilin Qu, Robert Harvey, @shivkumarmd!!! @jclinicalinvest @JCI_insight @UCLAHealth

Journal of Clinical Investigation @jclinicalinvest

2 weeks ago

This Research Letter reports a new role for Neuropeptide Y in #CardiacElectrophysiology: doi.org/10.1172/JCI204… Olujimi A. Ajijola @OluAjijola & team @UCLAHealth show Neuropeptide Y deficiency perturbs L-type calcium and outward potassium currents leading to ventricular

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Unraveling links between #Prediabetes, #CardiovascularDisease, and #HepaticSeatosis: doi.org/10.1172/jci.in… Tang et al. identified 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.

@JS_Pollock @UABNews Time-restricted feeding reverses kidney fibrosis through reduced CD8+ T cell infiltration in obese mice: doi.org/10.1172/jci.in…

Sunday read💫: Another piece of the pie for time restricted feeding: doi.org/10.1172/jci.in… Jennifer S. Pollock @JS_Pollock & team @UABNews discover time-restricted feeding reverses kidney fibrosis and damage in diet-induced obese mice by reducing the infiltration of pro-inflammatory immune cells, particularly those migrating from the small intestine and associated tissues. The image shows a whole mouse kidney for spatial analysis with regions of interest marked for the cortex (NCC staining, yellow) and the medulla (NKCC2 staining, orange).🧵 #KidneyFibrosis