Count down: Our top 5 most-accessed manuscripts of 2025! #3:Anti-inflammatory actions of glucagon-like peptide 1 medicines beyond metabolic benefits: doi.org/10.1172/JCI1... @danieljdrucker.bsky.social

Count down: Our top 5 most-accessed manuscripts of 2025! #4: Our gut microbiome and cancer response to immune checkpoint inhibitors: doi.org/10.1172/JCI1...

Count down: Our top 5 most-accessed manuscripts of 2025! #5: Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity: doi.org/10.1172/JCI1...

A High-Resolution Genomic Roadmap for Chronic Pain Converges on Glutamatergic Neurons and C-Fibers: doi.org/10.1172/JCI2... Erick J. Rodríguez-Palma & Rajesh Khanna @khannalabuf.bsky.social provide a Commentary on Sylvanus Toikumo et al. (doi.org/10.1172/JCI1...)

cGAS/STING-mediated γδ T cell recruitment drives radioresistance: implications for improving radioimmunotherapy outcomes: doi.org/10.1172/JCI2... Brooke C. Braman & David R. Raleigh comment on Yue Deng et al. doi.org/10.1172/JCI1...

Breast cancer stem cells drive resistance to standard therapies in triple-negative breast cancer. Here, Qing Zhang & team show targeting kinesin family member KIF20A in vitro and in mice sensitizes stem-like TNBC cells to standard chemotherapy: doi.org/10.1172/JCI1...

How can we improve the radiotherapy response? Chao Wan & team show the mechanism by which gamma delta T cells mediate radioresistance, highlighting IL-17 signaling & CCL20 as potential targets for enhancing radiosensitivity: doi.org/10.1172/JCI1...

Findings from Drs. Jennifer Grandis & Daniel Johnson in The Journal of Clinical Investigation support the development of precision medicine approaches for fanconi anemia - head & neck squamous cell carcinoma. ⬇️

Can we disrupt the amplification of systemic inflammation in sepsis? Ping Wang & team find neutrophils expressing high DLL4 induce pulmonary endothelial cell PANoptosis, exacerbating acute lung injury. And treatment with a Notch1 inhibitor in septic mice… 👉 doi.org/10.1172/JCI1...

A promising therapeutic in cardiac disease ASCI member Howard A. Rockman & team identify a small molecule β1AR allosteric modulator that suppresses exercise-induced ventricular tachycardia in a murine model of catecholaminergic polymorphic ventricular tachycardia: doi.org/10.1172/JCI1...

Previously shared: An activate-to-eliminate approach in HIV Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI197266

From earlier this week: From synaptogenic to synaptotoxic This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...

Providing a conceptual framework for targeting mitochondrial metabolism in immunotherapy & transplantation ASCI member Pavan Reddy & team show the mitochondrial complex II component SDHA as a key switch in CD4 & CD8 T cell metabolism, function & differentiation: doi.org/10.1172/JCI1...

From synaptic guardian to neurodegenerative culprit: rewiring the amyloid-β feedback loop in Alzheimer’s disease: doi.org/10.1172/JCI2... Commentary: Joachim Herz discusses Alberto Siddu et al. (doi.org/10.1172/JCI1...)

That gut feeling about your microbiome… In this Research Letter, Purna C. Kashyap & team report distinct small intestinal microbes underlie visceral hypersensitivity in a humanized mouse model: doi.org/10.1172/JCI1...

A widely held hypothesis posits that ER stress drives cell death in thyroid disease Here, Peter Arvan & team generate thyroglobulin KO mice, finding stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress: doi.org/10.1172/JCI1...

An activate-to-eliminate approach in HIV Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI1...

🔬 #CancerResearch Spotlight: AKT activation mitigates efficacy of androgen receptor (AR) targeted therapy in TMPRSS2:ERG fusion #ProstateCancer. 💡Patients with T:E fusion prostate cancer may benefit from combination therapy targeting AR and AKT. 📝Steven Balk MD, PhD, BIDMC @the-asci.org

Merkel cell polyomavirus can cause cancer, but how cells adopt a neuroendocrine state was unclear ASCI member Isaac Brownell & team find a unique interaction between the integrated virus and the host’s circuitry for neuroendocrine TFs in Markel cell carcinoma: doi.org/10.1172/JCI1...

There are currently no approved drugs for MASLD-induced hepatocellular carcinoma Here, Terence Lee & team target adipocyte-derived FABP4 in mice, blocking cancer stem cell-driven tumor growth: doi.org/10.1172/JCI1...

Helping cancer lose its grip Here, Pengda Liu & team show SPOP inhibitors act as molecular glue degraders, stabilizing and activating STING to enhance immunotherapy in melanoma mouse models: doi.org/10.1172/JCI1...

From synaptogenic to synaptotoxic This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neuronsbu free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...

A new platform for advanced prostate cancer ASCI member Steven P. Balk & team find AKT activation mitigates efficacy of AR targeted therapy in TMPRSS2:ERG fusion prostate cancer, suggesting combination therapy targeting AR and AKT in those with T:E fusion PCa: doi.org/10.1172/JCI1...

ICYMI: Adoptive transfer of Tregs can treat murine inflammatory disorders, but their efficacy in human disease have been variable. Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: buff.ly/LXh5WLN

ICYMI: A strategy for reversing age-related cardiovascular disease… @lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: buff.ly/WFh2EHL

FATP2 at the crossroads of fatty acid transport, lipotoxicity, and complex disease: doi.org/10.1172/JCI1... Paul N. Black & Concetta C. DiRusso provide a Commentary on Shenaz Khan et al. (doi.org/10.1172/JCI1...)

ZMIZ1 and estrogen receptor α form an essential partnership in endometrial biology: doi.org/10.1172/JCI1... This Commentary by Md Saidur Rahman, Kyeong A. So & Jae-Wook Jeong discusses Sylvia C. Hewitt et al.: doi.org/10.1172/JCI1...

The antibody Teplizumab can delay type 1 diabetes, but therapeutic responses are heterogeneous. Here, Conny Gysemans & team find variable patient responses align with specific immune gene signatures, offering a tool to predict treatment success or resistance: doi.org/10.1172/JCI1...

Our fresh and still-steaming Journal of Clinical Investigation preprint is out! 🚀 We explore how T-cell acute lymphoblastic leukemia (T-ALL) exploits inflammatory CXCR3–CXCL10 signaling within the meninges to drive CNS infiltration. www.jci.org/articles/vie...

Author Dr. Seth Zoth tells us about their discovery: A protective and heterosubtypic antibody lineage targeting the influenza A virus neuraminidase active site: doi.org/10.1172/JCI1...

James E. Crowe Jr. & team find an antibody lineage from a single donor that binds the active site of influenza neuraminidase, cross-reacts with antigenically diverse viruses, and protects mice from infection: doi.org/10.1172/JCI1...

ft. O. Paul, A. Shetty, J. Choi, M. Towers, L. Assi, J. Garifallou, K. Forrest, A. Cameron, @shaonsengupta.bsky.social (@chopresearch.bsky.social), T. Brooks (@itmat.bsky.social), A. Sehgal (Neuroscience) & G. Grant (@penngenetics.bsky.social) @jci.org www.jci.org/articles/vie...

The mechanistic basis of chronic liver disease is still only partially understood. ASCI member Harmeet Malhi & team discover ER-stress mediated S100A11 upregulation drives progression of fatty liver disease, revealing a new target for future treatments: doi.org/10.1172/JCI1...

For those interested in fertility regulation, endometriosis, adenomyosis, and endometrial cancer… Francesco J. DeMayo & team identify ZMIZ1 as a co-regulator of uterine estrogen signaling important in uterine health and pathology: doi.org/10.1172/JCI1...

Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development in mice Olga A. Guryanova & team report an aging-related condition caused by mutations in the blood system promotes obesity and drives the risk of #diabetes & #MASLD with a high-fat diet: doi.org/10.1172/JCI1...

Excited to share this work with @vaughalle1.bsky.social! Reduction of PAI-1 activity can slow - and even reverse - vascular aging

Linking primary cilia dysfunction to aortic conditions Georg Rosenberger & team reveal CDKL1 variants affecting ciliary formation predispose to thoracic aortic aneurysm and dissection: doi.org/10.1172/JCI1... Figure: expression of disease-associated CDKL1 variants increases bi-ciliated RPE-1 cells

A strategy for reversing age-related cardiovascular disease… @lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: doi.org/10.1172/JCI1...

Introducing a new player in GLP-1-regulated insulin secretion… Jeffrey R. Schelling & team find inhibition of the fatty acid transport protein FATP2 exerts glucose-lowering effects through GLP-1 secretion by alpha cells: doi.org/10.1172/JCI1...

Adoptive transfer of Tregs can treat murine inflammatory disorders, but their efficacy in human disease have been variable. Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: doi.org/10.1172/JCI1...

Finally out: FBXO11 loss establishes a stem cell program jci.org/articles/vie.... Many years and outstanding trainees and staff, including Hayle Kincross and Angela Wong, to get the manuscript over the finish line. @terryfoxresearch.bsky.social #CIHR @bccancerfdn.bsky.social #ubcpathology

ICYMI: This issue’s cover features work by Mustafa Tekin & team reporting on changes in the carboxypeptidase D gene as a cause congenital hearing loss by harming inner ear cells—with implications for targeting the nitric oxide pathway as a therapeutic strategy: doi.org/10.1172/JCI1...

From earlier this week: Let’s GIV a NOD(2) to gut homeostasis Here, Pradipta Ghosh & team find a critical interaction between GIV and NOD2 in gut macrophages, revealing their importance in maintaining gut health and preventing inflammatory bowel diseases: doi.org/10.1172/JCI1...

Braking the system: the aryl hydrocarbon receptor controls monocytes in homeostasis: doi.org/10.1172/JCI1... Jessica E. Kenison & @quintanalabhms.bsky.social comment on Adeline Cros et al.: doi.org/10.1172/JCI1...

Diabetes research enters the biobank era: searching for the truth in a deep well: doi.org/10.1172/JCI1... Decio L. Eizirik & Priscila L. Zimath comment on Theodore dos Santos et al.: doi.org/10.1172/JCI1...

Claudin-2 deficiency reveals a corticomedullary calcium gradient driving kidney stone formation: doi.org/10.1172/JCI2... Benjamin D. Humphreys @humphreyslab.bsky.social provides an Editor’s Note on Christine V. Behm et al. doi.org/10.1172/JCI1...

How do we restrict microbiota-driven responses that lead to autoimmunity? Here, Elodie Segura & team reveal aryl hydrocarbon receptor restrains tonic cytokine responses by inhibiting microbiota-sensing monocytes in mice and human samples: doi.org/10.1172/JCI1...

Molecular glue as a new therapeutic strategy in metastatic KRAS-mutant lung cancer @gouthamnarla.bsky.social & team combined a PP2A molecular glue with RAS/MAPK inhibitors to restore tumor-suppressor activity & overcome drug resistance in mice with metastatic KRAS-driven NSCLC: buff.ly/1HzFVe5

🔬 Pathway discovered to make the most common #breastcancer tumor responsive to #immunotherapy A new study led by @tceliaterrassa.bsky.social and published in @jci.org, supported by the Associació Espanyola Contra el #Càncer #recerca #TalentMAR #TalentoAECC researchmar.net/noticies/140...

~15 years ago, Dr. Fred Coe put forward the “vas washdown” model for explaining kidney stone formation @alanyuneph.bsky.social & team now report on a new mouse model, showing kidney-specific Cldn-2 KO leads to medullary nephrocalcinosis—supporting the vas washdown model: doi.org/10.1172/JCI1...