John K. Lee & team @fredhutch.org present a framework for combinations of Ab-drug conjugate targets & payloads that may be applied to improve metastatic, castration-resistant prostate cancer: doi.org/10.1172/JCI2... @the-asci.org

Over 50% of patients with neurodevelopmental disorders are still left without a genetic diagnosis: doi.org/10.1172/JCI1... Here, Dong Li & team identify biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder. with @reza-maroofian.bsky.social

How do high-risk APOL1 variants lead to kidney transplant rejection? doi.org/10.1172/JCI1... Madhav C Menon & team @yaleschoolofmed.bsky.social discover that APOL1 variants promote CD8 T-cell activation via Ca2+ signaling, causally explaining their link to kidney rejection. @the-asci.org

Drs. Chinnaiyan and Sawyers are recognized for their discoveries defining the molecular drivers of prostate cancer and pioneering precision therapies that have reshaped the diagnosis and treatment of prostate cancer worldwide. Read the full interview: doi.org/10.1172/JCI2...

The American Society for Clinical Investigation@the-asci.org · 2d ago

📣📣Announcing 🎉🎉 Arul M. Chinnaiyan, MD, PhD, and Charles L. Sawyers, MD, receive the 2026 Harrington Prize for Innovation in Medicine! See the interview on YouTube: youtu.be/JG-x6nnJi8E

Lymphatic therapies open the valve in Marfan syndrome: doi.org/10.1172/JCI2... Yanna Tian & Kathleen M. Caron provide a Commentary on Tan et al.: doi.org/10.1172/JCI1...

The cover of this issue highlights work by Tan et al. @feinberg.northwestern.edu on the contributions of lymphatic dysfunction and immune cell infiltration to mitral valve disease in a mouse model of Marfan syndrome: doi.org/10.1172/JCI1... Image generated using ChatGPT & Adobe Fresco

Sunday Spotlight💫: Targeting hepatic cholesterol sensing to tackle metabolic dysfunction–associated steatohepatitis: doi.org/10.1172/JCI2... Mengwei Zang and Yu Li provide a commentary on Deng et al. doi.org/10.1172/JCI1...

ICYMI: Revealing a potential target for fatty liver disease and related disorders: doi.org/10.1172/JCI1... Deng et al. identify the NFE2L1/INSIG1 axis that regulates a transcription factor important for lipid biosynthesis and VLDL secretion—helping to prevent cholesterol buildup & liver damage

The aggressive cancer cells featured in this image are undergoing cell death: doi.org/10.1172/JCI2... Here, Browne et al. @utoronto.ca establish a next-generation mouse model and identify Minnelide as a potential treatment for CIC::DUX4 sarcoma, a rare and deadly cancer with no treatment options

The gut-joint axis & the effects of antibiotics: doi.org/10.1172/JCI2... @msdiamondlab.bsky.social & team @washumedicine.bsky.social find antibiotics-triggered changes in the microbiome worsen alphavirus-induced arthritis in mice by modulating infiltrating & resident immune cells in joint tissues

Clonal hematopoiesis in patients with solid tumors is linked with higher mortality Arabzadeh et al. find cancer treatment creates positive selection pressure, reducing allelic diversity while promoting expansion of specific mutant clones associated with outcomes: doi.org/10.1172/JCI2...

Histone lysine methyltransferases KMT2C and KMT2D join the all-star tumor suppressor team in gastrointestinal cancer: doi.org/10.1172/JCI2... Nicole M. Peña Ruiz and Martin E. Fernandez-Zapico provide a commentary on Wang et al. doi.org/10.1172/JCI1... @the-asci.org

Targeting hepatic cholesterol sensing to tackle metabolic dysfunction–associated steatohepatitis: doi.org/10.1172/JCI2... Mengwei Zang and Yu Li provide a commentary on Deng et al. doi.org/10.1172/JCI1...

Revealing a potential target for fatty liver disease and related disorders: doi.org/10.1172/JCI1... Deng et al. identify the NFE2L1/INSIG1 axis that regulates a transcription factor important for lipid biosynthesis and VLDL secretion—helping to prevent cholesterol buildup & liver damage

A highlight from last week💫: Antigen-specific type 1 regulatory T cell responses shape immunity and disease tolerance in human malaria: doi.org/10.1172/JCI2... Leonie Brockmann comments on Nideffer et al. doi.org/10.1172/JCI2... @prasannaj77.bsky.social

Spotlight💫: Can we reverse immunosuppression in glioblastoma? doi.org/10.1172/JCI1... Daniel J. Brat & team discover a pathway that glioblastoma cells use to activate macrophages and suppress anti-tumor immunity, revealing the PDPN-CLEC5A-Syk pathway as a potential therapeutic target. @the-asci.org

SEC16B identified as a regulator of VLDL secretion and lipid accumulation in the liver: doi.org/10.1172/JCI2... Hossein Ardehali @hosseinardehali.bsky.social provides a commentary on Lu et al. doi.org/10.1172/JCI2... @the-asci.org

Review: Sterol biosynthesis, brain development, and disease: doi.org/10.1172/JCI2... Peeples et al. @unmcmmi.bsky.social & @unmc.bsky.social summarize functions of cholesterol in neurodevelopment and the potential consequences of genetic factors and medications that disrupt cholesterol biosynthesis

H. Bellen, S. Lu, J. Shulman, Z. Liu et al explain in @jci.org a new way #epilepsy can happen. @bcmhouston.bsky.social #TexasChildrens @bcmgenetics.bsky.social #diagnosis blogs.bcm.edu/2026/07/23/r...

Researchers uncovered a novel pathway that causes epilepsy

The findings also provide a new approach to improve the diagnosis of epilepsy, for which a genetic cause cannot be found in about 50 % of individuals with the condition.

blogs.bcm.edu

Providing valuable resources for the study of gastric cancer: doi.org/10.1172/JCI1... Yu Chen & team modeled gastric cancer progression with KO mice, finding deficiency of Kmt2c & Kmt2d led to dysplasia and loss of both genes with Pten resulted in invasive adenocarcinoma. @the-asci.org

How do liver cells determine whether lipids are stored or secreted? doi.org/10.1172/JCI2... Bo Wang & team report SEC16B helps manage lipids by balancing lipid release and storage—and its inhibition in mice lowers blood lipids and reduces atherosclerosis.

Despite decades of study, the mechanisms driving sepsis-associated organ dysfunction remain elusive doi.org/10.1172/JCI2... Here, Robert B. Lindell & team identify a unique immune profile in children with sepsis linked to outcomes and reveal JAK/STAT as a candidate target.

Presenting a valuable intestinal cell atlas: doi.org/10.1172/JCI2... Michael G Kattah & team @ucsanfrancisco.bsky.social applied spatial gene mapping to archived colitis biopsies, identifying immune cell neighborhoods that explain why some patients are resistant to vedolizumab & others respond well

Antigen-specific type 1 regulatory T cell responses shape immunity and disease tolerance in human malaria: doi.org/10.1172/JCI2... Leonie Brockmann comments on Nideffer et al. doi.org/10.1172/JCI2... @prasannaj77.bsky.social

This malaria study has relevance to other high-antigen settings: doi.org/10.1172/JCI2... @prasannaj77.bsky.social & team @stanfordmedicine.bsky.social found children with high Tr1 frequencies were protected from symptomatic malaria despite parasitemia but also experienced delayed parasite clearance

JCI - Rheumatoid factor production is genetically and molecularly distinct from rheumatoid arthritis www.jci.org/articles/vie...

Review: The splice of life: an isoform-centric view of disease, technology, and therapeutics: doi.org/10.1172/JCI2... Pan et al. discuss the functional effects of transcript isoforms in disease while summarizing technological advances in RNA sequencing and splicing-based therapeutics.

Can we reverse immunosuppression in glioblastoma? doi.org/10.1172/JCI1... Daniel J. Brat & team discover a pathway that glioblastoma cells use to activate macrophages and suppress anti-tumor immunity, revealing the PDPN-CLEC5A-Syk pathway as a potential therapeutic target. @the-asci.org

In Case You Missed It ⭐️ Aging-associated changes in bone remodeling can influence neurovascular compartments. In this Review, Jiekang Wang et al. explore the bone-cerebrovascular axis and the effects of bone aging on neurovascular dysfunction and neurodegeneration: doi.org/10.1172/JCI2...

Saturday spotlight: New information on how estrogen impacts the heart: doi.org/10.1172/JCI2... Using iPCs and two rodent models, Kurt W. Prins @kurtprins.bsky.social @the-asci.org & team find estrogen exerts cardioprotective effects by regulating microtubules.