Unleashing c-KIT activates maladaptive vascular remodeling in HHT doi.org/10.1172/JCI1... Gahn et al. show that SMAD4 limits c-KIT expression in endothelial cells. In a SMAD4-deficient HHT model, c-KIT derepression dysregulated mechanosensory-driven vascular remodeling.

Abnormal role of c-KIT in vascular endothelium drives brain AVMs doi.org/10.1172/JCI1... Drapé et al. show that pro-angiogenic c-KIT+ endothelial states induce brain arteriovenous malformations in an ALK1-deficient model of hereditary hemorrhagic telangiectasia.

Viewpoint: Small populations, big impact: Leveraging rare disease gene therapies to benefit millions: doi.org/10.1172/JCI2... Stephanie Cherqui discusses discoveries in rare disease research that have changed therapeutic principles for other diseases.

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Chenxu Guo & Leif W. Ellisen present: Antibody-drug conjugates in #BreastCancer: redefining targeted therapy: doi.org/10.1172/JCI2...

Why a positive rheumatoid factor test does not always mean rheumatoid arthritis: doi.org/10.1172/JCI2... Luc Van Kaer comments on Hocaoglu and Sawalha: doi.org/10.1172/JCI2...

Clarifying rheumatoid factor’s relationship to rheumatoid arthritis doi.org/10.1172/JCI2... Mehmet Hocaoglu & Amr H. Sawalha identify immune and genetic signatures unique to RF autoantibody production, providing insight into pathways involved in RF-to-RA progression.

ICYMI💫: A potential therapeutic target for liver failure. Tong et al. @uniheidelberg.bsky.social explore the repair process in liver failure using several models, reporting that TGF-β serves as a critical signaling determinant of liver progenitor cell activation & function: doi.org/10.1172/JCI1...

Weekend Highlight💫: Could excess complement activation lead to more thrombosis and miscarriages? doi.org/10.1172/JCI2... Using mouse models, Smid et al. reveal cooperation between platelets, coagulation, and complement in establishing maternal blood flow to the placenta.

All in the family: a population-scale perspective on genetic networks of autoimmune disease: doi.org/10.1172/JCI2... Arielle Klepper, Mark S. Anderson provide a Commentary on Eriksson et al.: doi.org/10.1172/JCI2...

What 3,839,400 sibling pairs can tell us about autoimmune disease: doi.org/10.1172/JCI2... Eriksson et al. @ki.se quantified genetic correlations across 22 autoimmune diseases, showing substantial cluster-specific genetic overlap that largely aligns with affected tissue types

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Fanucci et al. present: Toward targeted therapeutics for lobular breast cancer: doi.org/10.1172/JCI2... stoverlab.bsky.social

The promise of new approach methodologies: doi.org/10.1172/JCI2... In this Review, Joseph C. Wu & colleagues describe how new approach methodologies—human cell-based technologies and computational models—could improve cardiometabolic drug development.

The promise of new approach methodologies: doi.org/10.1172/JCI2... In this Review, Joseph C. Wu & colleagues describe how new approach methodologies—human cell-based technologies and computational models—could improve cardiometabolic drug development.

As part of JCI’s review series on emerging therapeutic strategies in #BreastCancer, Walmsley et al. present: Expanding the therapeutic scope of PARP inhibitors in breast cancer: current indications and future directions: doi.org/10.1172/JCI2...

Targeting neutrophil effector function reduces GVHD: doi.org/10.1172/JCI2... Cover: Holzmüller et al. @uniklinik-fr.bsky.social report that pegtarazimod, a peptide drug that reduces neutrophil effector functions, limits acute GVHD mortality & severity in mice and is tolerated in patients.

Could targeting LSD1 be a novel strategy to decrease senescence, organ aging, and hair graying? doi.org/10.1172/JCI1... Zhang et al. demonstrate LSD1 as a key regulator of DNA damage-induced senescence and organ aging and highlights it as a promising therapeutic target.

Casalino-Matsuda et al. analyzed serially collected alveolar samples from unvaccinated patients with severe #SARSCoV2 pneumonia treated with Auxora vs placebo & find Auxora reprograms pathogenic alveolar macrophage–T cell circuits in viral pneumonia: doi.org/10.1172/JCI2... catgaohow.bsky.social

For the first time, gene therapy successfully treats Cockayne Syndrome in mice: doi.org/10.1172/JCI1... Batista et al. show the AAV-mediated gene therapy corrected the DNA damage hypersensitivity of CSA-deficient human cells extended lifespan safely in mice.

Presenting phosphorylated FADD as a novel driver of resistance in breast cancer: doi.org/10.1172/JCI1... Awadia et al. find that blocking FADD phosphorylation restored CDK4/6 inhibitor sensitivity and improved tumor control in resistant ER+ breast cancer models.

Sunday Read💫: The difference between cysts & no cysts in polycystic kidney disease. Li et al. @yalenephrology.bsky.social show that upstream protein translation on the PKD1 transcript blunts PC1 expression & can be blocked to therapeutically increase expression in PKD: doi.org/10.1172/JCI2...

Weekend highlight💫: Targeting ferroptosis in heart and kidney disease: doi.org/10.1172/JCI2... In this Review, Hossein Ardehali @hosseinardehali.bsky.social & colleagues describe the diverse physiological and pathological roles of ferroptosis and its potential as a therapeutic target.

A potential therapeutic target for liver failure. Tong et al. @uniheidelberg.bsky.social explore the repair process in liver failure using several models, reporting that TGF-β serves as a critical signaling determinant of liver progenitor cell activation & function: doi.org/10.1172/JCI1...

Could excess complement activation lead to more thrombosis and miscarriages? doi.org/10.1172/JCI2... Using mouse models, Smid et al. reveal cooperation between platelets, coagulation, and complement in establishing maternal blood flow to the placenta.

From silos to synergy: The interdisciplinary discovery potential in redefining polyendocrine metabolic ovarian syndrome: doi.org/10.1172/JCI2... Morhaus et al. provide a Commentary on Morhaus et al.: doi.org/10.1172/JCI1... #PMOS #PCOS

Highlighting the genetic architecture bridging ovarian and metabolic mechanisms in PMOS doi.org/10.1172/JCI1... Nguyen et al. integrate human and mouse genetic data to reveal connections between reproductive, endocrine, and cardiometabolic aspects of PMOS/PCOS.

The difference between cysts & no cysts in polycystic kidney disease: doi.org/10.1172/JCI2... Li et al. @yalenephrology.bsky.social show that upstream protein translation on the PKD1 transcript blunts Polycystin-1 expression & can be blocked to therapeutically increase expression in PKD

Going to the source: pancreatic lymph nodes maintain stem-like CD8+ T cells in human type 1 diabetes: doi.org/10.1172/JCI2... Fatoumata Samassa, Sylvaine You, & Roberto Mallone @institutcochin.bsky.social write a Commentary on Peters et al.: doi.org/10.1172/JCI1...

I’m very happy to share that our work looking at the role of B cell lipid metabolism in driving response to vaccination during immunosuppression is now (finally!) out online and published as an in press preview at JCI - www.jci.org/articles/vie...

Pancreatic lymph nodes house T1D-like CD8 T cells with self-renewing features doi.org/10.1172/JCI1... Todd M Brusko @bruskolab.bsky.social & team profiled T cells in T1D, highlighting a stem-like population in lymph nodes as a potential source for pancreatic autoreactive T cells.

1/ Highlighting authors behind the Cover💫: Coauthors (from left to right), Manal Mazloum, Frank Bienaimé, Vicky Scata, & Rushdi Alghamdi are featured here working @inem-necker.bsky.social in Paris, France with one of the TEM microscopes used to demonstrate basement membrane thinning in #ADPKD