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 er 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

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.in…
Mapping vascular plasticity during fibrogenesis identifies othelial 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).

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 express increasing amounts of TAGLN (red) going counterclockwise.

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.in…

Sandra M. Blois @Blois_Lab & team established a pregnant mouse model for investigating the effects of Vpregnancy outcomes and fetal development. Vaccination at various gestation revealed early timepoints raised pregnancy loss.
#Vaccines

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.in…
Using a murine colitis model, the researchers reveal how HECTD3 controls immune colootects against colitis by restricting MyD88 activation and signaling.
@gur_ola @mariola_ferraro @gatechatl
#colitis

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.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@UVAd Inhibition of DYRK1A using LCTB-92 induces cardand 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

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

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-Muriluring 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. 🧵

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 tm. 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

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 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, suppmyeloid 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

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 rediabetes. 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.

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 syndodeficiency #IntestinalInflammation

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