Location, location, location—in Inflammatory bowel disease doi.org/10.1172/JCI2... Ken S. Lau & team use a unique model of Crohn’s disease, reporting on Chlamydia and genetic risk as a trigging combination for Crohn’s disease-like inflammation in the proximal colon.

Neuromyelitis optica is a severe nervous system disease in which early lesions show neutrophil infiltration doi.org/10.1172/JCI1... Long-Jun Wu & team establish a mouse NMO model, discovering motor dysfunction is driven by neutrophil-microglia interaction through C5a/C5aR1 signaling

Lysosomal homeostasis at the crossroads of neurodegeneration: doi.org/10.1172/JCI1... In JCI’s Review Series on Neurodegeneration, Stefano De Tito & Sharon A. Tooze consider lysosomes in an integrated network of organelles that collectively sustain neuronal metabolism & stress resilience

How do lung epithelial stem cells generate one of the thinnest and largest cell type in our body? Konishi et al. report on a unique thick microtubule bundle organization required to generate expansive & thin cell morphology of during AT2 differentiation into AT1s: doi.org/10.1172/JCI1...

Clarifying the connection between the gut microbiome & lower GI toxicity of NSAIDs… Emanuela Ricciotti & team report concomitant COX-1 & COX-2 suppression is insufficient to induce enteropathy associated with chronic NSAID use: doi.org/10.1172/JCI1... Ronan Lordan @elronan.bsky.social

Congratulations Qing and Team on this exciting work www.jci.org/articles/vie...

New work with contribution from former #ListerFellow @jamesnathanlab.bsky.social that reveals a new target mechanism to overcome therapeutic resistance in kidney cancer.

Addressing a longstanding question in HIV Here, Afam A. Okoye & team show a vaccine strategy for boosting virus-specific CD8+ T cells in SIVmac239-infected macaques on ART delays viral rebound & promotes early control of viral replication during ART interruption: doi.org/10.1172/JCI1...

The PIM kinase family is involved in tumorigenesis. Here, Xue-Zhong Yu & team identify Pim2 as a key negative regulator of CD8 T-cell antitumor immunity and validate it as a potential therapeutic target for enhancing cancer immunotherapy: doi.org/10.1172/JCI1...

Spotlight: In 1925, the Cori chicken-wing experiment measured tumor metabolism by comparing venous outflow from tumor & control wings Here, @mvhlab.bsky.social & team directly assess nutrient use by lung cancer via intraoperative sampling of blood entering & leaving the lung doi.org/10.1172/JCI1...

ICYMI: Gut microbes sound the alarm during sleep loss doi.org/10.1172/JCI1... Leone et al. find short-term sleep restriction in healthy humans alters 24-hr rhythmic profiles of circulating microbially derived metabolites, including butyric acid & tryptophan catabolites, relative to habitual sleep

Mismatch repair deficiency reshapes glioblastoma through immune suppression rather than hypermutation: doi.org/10.1172/JCI2... Craig Horbinski & colleagues provide a Commentary on Montserrat Puigdelloses Vallcorba et al.: doi.org/10.1172/JCI1...

The Bug, The Burden, and The Biology: Beyond Host-Centric Phenotyping in Sepsis: doi.org/10.1172/JCI2... Georgios D. Kitsios & Rebecca M. Baron comment on Rishi Chanderraj et al.: doi.org/10.1172/JCI1...

ADAMTS7 has been repeatedly associated with coronary artery disease. Here, Robert C. Bauer & team demonstrate that ADAMTS7 is expressed across multiple vascular cell types & contributes to atherosclerosis by promoting lipid accumulation in smooth muscle cells: doi.org/10.1172/JCI1...

In 1925, the Cori chicken-wing experiment measured tumor metabolism by comparing venous outflow from tumor & control wings Here, @mvhlab.bsky.social & team directly assess nutrient use by lung cancer via intraoperative sampling of blood entering & leaving the lung: doi.org/10.1172/JCI1...

Challenging the host-centric paradigm in sepsis! Robert P. Dickson & team find sepsis heterogeneity is shaped not only by host factors but also by pathogen identity, burden, and virulence, advancing the precision-medicine approach to sepsis: doi.org/10.1172/JCI1...

Gut microbes sound the alarm during sleep loss Leone et al. find short-term sleep loss in healthy humans alters 24-hr rhythmic profiles of circulating microbially derived metabolites, including butyric acid & tryptophan catabolites, relative to habitual sleep: doi.org/10.1172/JCI1...

Addressing an urgent translational need for patients with hereditary cancer syndromes caused by MMR mutations! Hambardzumyan & team reveal a role for MMR genes in tumor growth and temozolomide resistance & present KL-50 as a therapeutic avenue using new models: doi.org/10.1172/JCI1...

A mouse disease model for parkinsonism with psychiatric features Freja Herborg & team explore the behavioral & neurochemical changes that arise from patient-derived mutations in dopamine transporter associated with parkinsonism & neuropsychiatric disease: doi.org/10.1172/JCI1...

ICYMI: Protecting against atherosclerosis! This Issue’s cover features work by Xunde Xian & team demonstrating KIF13B has an essential role in the stabilization of atherosclerotic plaques using human plaque tissue and mouse models: doi.org/10.1172/JCI1...

Early-career biomedical scientists, this one’s for you! 🧪 Submit a 2-minute (or shorter) video by Apr 2 on a research question you’re studying. We'll announce up to 3 winners on social and in our newsletter in July, to be featured in the Journal of Clinical Investigation: https://ow.ly/yXNi50Yo95b

From earlier this week: A novel disease mechanism in partial lipodystrophy syndrome disease doi.org/10.1172/JCI1... Elif Oral & team describe a nonsense EBF2 variant in a patient with atypical PLD & establish a mouse model—linking the EBF2 variant to impaired adipogenesis & adipose tissue function

Hitting the hidden: arming the immune system for the next zoonotic coronavirus spillover: doi.org/10.1172/JCI2... Charlie Fricke & Stanley Perlman comment on Nicholas You Zhi Cheang et al.: doi.org/10.1172/JCI1...

New paper from Dr. Wen Gu on the impact of L-2-hydroxyglutarate deficiency on neural stem cell function and neuronal differentiation. Interesting connection between an IEM and chronic oncogene activation. Thanks to Dr. Bushra Afroze and her patients for participating. www.jci.org/articles/vie...

TMPRSS2:ERG–directed radiosensitization: exploiting DNA repair rewiring in gene fusion–positive prostate cancer: doi.org/10.1172/JCI2... Xiaoju Wang & Arul M. Chinnaiyan provide a Commentary on Köcher et al.: doi.org/10.1172/JCI1...

Facilitating precision therapy in prostate cancer Köcher et al. discover ERG overexpression as a biomarker for identifying patients with prostate cancer who can benefit from PARPi-based radiosensitization, enhancing radiotherapy efficacy & reducing toxicity: doi.org/10.1172/JCI1...

What we should be doing, but we're not: "Arming the immune system for the next zoonotic coronavirus spillover" A nasal dendritic-cell targeting vaccine that prevents viral transmission vs pan-sarbecovirus clades (i.e. all coronaviruses, irrespective of variants) www.jci.org/articles/vie...

A key feature of primary aldosteronism is adrenal gland hyperplasia Here, ASCI member David T. Breault & team show Rho/ROCK signaling and α-catenin mediates β-catenin-driven hyperplasia in the adrenal cortex via adherens junctions: doi.org/10.1172/JCI1...

Decoding neurodegeneration one cell at a time As part of the JCI’s Review Series on Neurodegeneration, Olivia Gautier, Thao P. Nguyen & Aaron D. Gitler summarize recent advances & applications of single-cell genomic approaches to study neurodegenerative disease: doi.org/10.1172/JCI1...

A novel disease mechanism in partial lipodystrophy syndrome disease doi.org/10.1172/JCI1... Elif Oral & team describe a nonsense EBF2 variant in a patient with atypical PLD & establish a mouse model—linking the EBF2 variant to impaired adipogenesis & adipose tissue function

Why do women account for nearly 2/3rd of all cases of Alzheimer's disease? A new, thorough review, open-access, on its origins in midlife. @jci.org www.jci.org/articles/vie...

Follow your nose! Sylvie Alonso & team develop a nasal vaccine booster that induces robust and sustained, cross-clade systemic and mucosal protective immunity in COVID19 mRNA vaccinated populations: doi.org/10.1172/JCI1...

Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD In the JCI’s Review Series on Neurodegeneration, Sami J. Barmada and colleagues explore alternative TARDBP splicing in shaping TDP43 function and disease pathogenesis: doi.org/10.1172/JCI1...

Women’s midlife: the front line of Alzheimer’s prevention In JCI’s Review Series on Neurodegeneration, Lisa Mosconi calls for a paradigm shift that validates midlife neuroendocrine aging as a distinct window of vulnerability and an opportunity for prevention: doi.org/10.1172/JCI1...

Protecting against atherosclerosis! This Issue’s cover features work by Xunde Xian & team demonstrating KIF13B has an essential role in the stabilization of atherosclerotic plaques using human plaque tissue and mouse models: doi.org/10.1172/JCI1...

Patients with recurrent kidney stone disease stand to benefit from personalized diagnostics. Here, Ruxandra Bachmann-Gagescu & team perform deep biochemical phenotyping, revealing prognostic value of rare genetic variants in adult kidney stone disease: doi.org/10.1172/JCI1...

ICYMI: These two transcription factors are required for regenerative lymphangiogenesis & repair following injury👇 Yang et al. establish ERG and Fli1 as core transcriptional regulators of lymphatic identity, integrity, and function, using human cells and mouse models: doi.org/10.1172/JCI1...

Previously shared: Do we need better ways to detect CHIP? Alexander G. Bick, @yashpershad.bsky.social et al. & team find epidemiology studies underestimate the strength of the association between clonal hematopoiesis & disease due to false negatives from shallow, WGS vs TGS: doi.org/10.1172/JCI1...

Tumor-intrinsic chromatin programs enforce immune evasion in glioblastoma: doi.org/10.1172/JCI2... Rongze Olivia Lu & colleagues provide a Commentary on Xinchun Zhang et al.: doi.org/10.1172/JCI1...

Safeguarding lymphatic identity: cooperative ERG-FLI1 activity in lymphatic vascular homeostasis: doi.org/10.1172/JCI2... Kelly de Korodi & Tatiana V. Petrova @petrovalab.bsky.social comment on Yang et al.: doi.org/10.1172/JCI1...

CD38 expression by neonatal human naïve CD4+ T cells shapes their distinct metabolic and tolerogenic properties @jci.org @ucsfmedicine.bsky.social www.jci.org/articles/vie...

Organized immunity in the CNS: What stroke reveals about neuroinflammation and lymphoid niches: doi.org/10.1172/JCI2... Catalina Lee-Chang comments on Yang et al.: doi.org/10.1172/JCI1...

JCI - Impaired glycosylation promotes rapid transition to hepatocellular carcinoma in model of diet induced steatotic liver disease www.jci.org/articles/vie...

These two transcription factors are required for regenerative lymphangiogenesis & repair following injury👇 Yang et al. establish ERG and Fli1 as core transcriptional regulators of lymphatic identity, integrity, and function, using human cells and mouse models: doi.org/10.1172/JCI1...

Glioblastoma remains profoundly resistant to immunotherapy Fanghui Lu & team show OLIG2, a master transcription factor in glioblastoma stem cells, enables immune evasion by suppressing CXCL10. Targeting OLIG2 overcomes immunotherapy resistance & improves survival: doi.org/10.1172/JCI1...

WHIM syndrome is a rare, autosomal dominant primary immunodeficiency disorder. ASCI member Philip M. Murphy & team report CRISPR silencing of Cxcr4 corrects leukopenia in a WHIM syndrome model, demonstrating a new strategy for dominant immune disorders: doi.org/10.1172/JCI2...

Do we need better ways to detect CHIP? Alexander G. Bick, @yashpershad.bsky.social et al. & team find epidemiology studies underestimate the strength of the association between clonal hematopoiesis & disease due to false negatives from shallow, WGS vs TGS: doi.org/10.1172/JCI1...

Breast cancer is associated with SIRT2 loss & genomic instability, but the precise mechanism has been unclear ASCI member David S. Yu & team now show SIRT2 deacetylates MRE11, facilitating DNA binding to promote DNA end resection and ATM-dependent DNA damage signaling: doi.org/10.1172/JCI1...

The FNDC4 gene has been associated with alcohol use disorder risk & treatment response Zhu et al. now report on neural organoids from WT and FNDC4 KO, finding the FNDC4 gene affects alcohol use disorder risk & drug treatment outcomes by altering neurogenesis: doi.org/10.1172/JCI1...

Using complementary models of ischemic stroke, Yang et al. show microglia recruit B cells into ischemic lesions through MIF/CD74/CXCR4 in early post-stroke stages, with interferon signaling in B cells to drive neuroinflammation and brain injury at later stages: doi.org/10.1172/JCI1...