The Journal of Clinical Investigation

The Journal of Clinical Investigation is a leading platform for breakthroughs in both basic and clinical biomedical research that aim to enhance medical practice.

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FGFR3-induced Y158 PARP1 phosphorylation promotes PARP-inhibitor resistance via BRG1/MRE11-mediated DNA repair in breast cancer models

5 days ago | jci.org | Mei-Kuang Chen |Hirohito Yamaguchi |Yuan Gao |Weiya Xia

ResearchOncologyOpen Access | 10.1172/JCI173757 J Clin Invest. https://doi.org/10.1172/JCI173757. Copyright © 2025, Chen et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Therapeutic B cell depletion identifies immunoregulatory networks

5 days ago | jci.org | Carolina M. Polonio |Francisco J. Quintana |Jessica Wei |Pierre-Paul Axisa

AbstractB cell depletion is a highly effective therapy in multiple sclerosis (MS), reducing inflammation and restoring immune balance. In this issue of the JCI, Wei et al. used single-cell RNA-Seq and flow cytometry, identifying the comprehensive effects of B cell depletion on the immune response, including an increase in antiinflammatory cerebrospinal fluid macrophages and elevated TNF-α expression by peripheral CD16+ monocytes.
Hyperinsulinemia-induced upregulation of adipocyte TPH2 contributes to peripheral serotonin production, metabolic dysfunction, and obesity

6 days ago | jci.org | Brian Park |Andrew Reeves |Ying Zhu |Robin Wilson

ResearchEndocrinologyMetabolismOpen Access | 10.1172/JCI190765 J Clin Invest. https://doi.org/10.1172/JCI190765. Copyright © 2025, Park et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. View PDF AbstractTryptophan hydroxylase (TPH) is a rate-limiting enzyme for serotonin or 5-hydroxytryptamine (5-HT) synthesis.
Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy

3 weeks ago | jci.org | Rocio Bengoechea |Andrew Findlay |Ankan K. Bhadra |Hao Shao

CorrigendumOpen Access | 10.1172/JCI194757 Published inVolume 135, Issue 10onMay 15, 2025J Clin Invest. 2025;135(10):e194757. https://doi.org/10.1172/JCI194757. © 2025 Bengoechea et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. View PDF Rocio Bengoechea, … , Heather L. True, Conrad C.
Endothelial dysfunction in patients with type 2 diabetes: the truth is in the blood

3 weeks ago | jci.org | Sarah Costantino |Shafeeq A. Mohammed |Francesco Paneni |Aida Collado

AbstractEndothelial dysfunction remains a cornerstone of diabetic vascular complications. RBCs emerge as pivotal players in endothelial dysfunction, yet the underlying mechanisms remain elusive. In this issue of the JCI, Collado et al. show that the detrimental action of RBCs on the endothelium is mediated by extracellular vesicles (EVs).
Genetic variants predisposing to increased risk of kidney stone disease

3 weeks ago | jci.org | Catherine E. Lovegrove |Michelle Goldsworthy |Jeremy S Haley |Jérémy Haley |Diane Smelser

Clinical Research and Public HealthEndocrinologyGeneticsNephrologyOpen Access | 10.1172/JCI186915 J Clin Invest. https://doi.org/10.1172/JCI186915. Copyright © 2025, Lovegrove et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The multiverse of CD46 and oncologic interactions

1 month ago | jci.org | M. Kathryn Liszewski |John Atkinson

AbstractInitially identified as a regulator of complement activation on host cells, the known roles of CD46 (membrane cofactor protein [MCP]) have expanded. We now know that this ancient molecule is expressed on almost all nucleated cells as a family of four predominant isoforms. It also is involved in human reproduction, modulation of T cell activation and immunoinflammatory effector functions, autophagy, and the newly identified intracellular complement system (complosome).
Fat, fibrosis, and the future: navigating the maze of MASLD/MASH

2 months ago | jci.org | Scott Friedman

The worldwide challenge of metabolic dysfunction–associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction associated steatohepatitis (MASH), has crept into our world. Previously referred to as NAFLD and NASH, respectively, these illnesses affect 30%–40% of the world’s population and are not confined to developing countries, rather affecting all regions except sub-Saharan Africa (1, 2).
Metabolic dysfunction-associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations

2 months ago | jci.org | Bernd Schnabl |Christopher J. Damman |Rotonya M. Carr

AbstractMetabolic dysfunction–associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis.
Ending one conversation, starting another

2 months ago | jci.org | Ushma S. Neill

With this entry, the Conversations with Giants in Medicine series comes to a close. The JCI is heading in a new direction with its video content, and I too will be heading in a different career direction that makes it hard to continue the series with the same care. As is often noted, “All good things must come to an end.” To watch a supercut of the last question I asked each subject, “What other vocation could have kept you as motivated?” see the JCI website at https://www.jci.org/videos/cgms.