Journal of Clinical Investigation
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JCI: April 15, 2025, issue

Read full issue (Volume 135, issue 8)

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On the cover:

Chaturantabut et al. identify biparatopic FGFR2 antibodies that are effective against FGFR2 fusion–driven cholangiocarcinoma. The cover art depicts biparatopic antibodies binding to and crosslinking FGFR2, creating large complexes that promote FGFR2 internalization and degradation, which ultimately suppress tumor growth. Image credit: Behnoush Hajian and Mrinal Shekhar.

Letters to the Editor
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Clinical evidence for independent regulation of vitamin D by intestinal CYP24A1
Sandrine Lemoine, Arnaud Molin, Alice Koenig, and Justine Bacchetta
Clinical evidence for independent regulation of vitamin D by intestinal CYP24A1. Reply.
Michaela A.A. Fuchs and Myles Wolf
Review
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Immunotherapeutic strategies in head and neck cancer: challenges and opportunities
Xia Liu, R. Alex Harbison, Mark A. Varvares, Sidharth V. Puram, and Guangyong Peng
Commentaries
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Serotonin sets up neutrophil extracellular traps to promote neuroendocrine prostate cancer metastasis in the liver
Dean G. Tang
Haptenization as the missing link between vasculitis and myeloperoxidase
Laura Santambrogio
Transient pain and long-term gain: adjuvant dose directs immune memory
Pabitra B. Pal and Smita S. Iyer
Developing cell-based therapies for pancreatic ductal adenocarcinoma
Rachel Elizabeth Ann Fincham, Joe Poh Sheng Yeong, and Hemant Mahendrakumar Kocher
Research Letters
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A dominant-negative IFNGR1 variant reveals broad immune cell sequestering of IFN-γ
Samantha Chan, Mai B. Margetts, Longfei Wang, Jack Godsell, Josh Chatelier, Belinda Liu, Charlotte A. Slade, Andrew Brett, Kasha P. Singh, Vanessa L. Bryant, and Lauren J. Howson
Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling
Yue Zhang, Julia A. Yescas, Kristy Tefft, Spencer Ng, Kevin Qiu, Erica B. Wang, Shifa Akhtar, Addie Walker, Macartney Welborn, Martin Zaiac, Joan Guitart, Aamir M. Qureshi, Youn H. Kim, Michael S. Khodadoust, Naiem T. Issa, and Jaehyuk Choi
Research articles
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AIDS/HIV

The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in nonhuman primates
Parham Ramezani-Rad, Ester Marina-Zárate, Laura Maiorino, Amber Myers, Katarzyna Kaczmarek Michaels, Ivan S. Pires, Nathaniel I. Bloom, Mariane B. Melo, Ashley A. Lemnios, Paul G. Lopez, Christopher A. Cottrell, Iszac Burton, Bettina Groschel, Arpan Pradhan, Gabriela Stiegler, Magdolna Budai, Daniel Kumar, Sam Pallerla, Eddy Sayeed, Sangeetha L. Sagar, Sudhir Pai Kasturi, Koen K.A. Van Rompay, Lars Hangartner, Andreas Wagner, Dennis R. Burton, William R. Schief, Shane Crotty, and Darrell J. Irvine
Pabitra B. Pal and Smita S. Iyer

Autoimmunity

Sequential carbonyl derivatives and hydrazone adduct formation on myeloperoxidase contribute to development of ANCA vasculitis
Gang Xi, Elizabeth A. Mclnnis, Olivier Lardinois, Peiqi Hu, John S. Poulton, Meghan E. Free, Dhruti P. Chen, Evan M. Zeitler, Eveline Y. Wu, Nicole M. Orzechowski, Vimal K. Derebail, J. Charles Jennette, and Ronald J. Falk

Genetics

Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome
Usua Oyarbide, Valentino Bezzerri, Morgan Staton, Christian Boni, Arish Shah, Marco Cipolli, Eliezer Calo, and Seth J. Corey
An inherited predisposition allele promotes gastric cancer via enhancing deubiquitination-mediated activation of epithelial-to-mesenchymal transition signaling
Bolin Tao, Zhenning Wang, Xuanyi Wang, Aixia Song, Jiaxian Liu, Jianan Wang, Qin Zhang, Zhaolin Chen, Zixian Wang, Wenjie Xu, Menghong Sun, Yanong Wang, Ping Zhang, Tao Xu, Gong-Hong Wei, Fei Xavier Chen, and Mengyun Wang
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Hematology

ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders
Christopher M. Sande, Stone Chen, Dana V. Mitchell, Ping Lin, Diana M. Abraham, Jessie Minxuan Cheng, Talia Gebhard, Rujul J. Deolikar, Colby Freeman, Mary Zhou, Sushant Kumar, Michael Bowman, Robert L. Bowman, Shannon Zheng, Bolormaa Munkhbileg, Qijun Chen, Natasha L. Stanley, Kathy Guo, Ajibike Lapite, Ryan Hausler, Deanne M. Taylor, James Corines, Jennifer J.D. Morrissette, David B. Lieberman, Guang Yang, Olga Shestova, Saar Gill, Jiayin Zheng, Kelcy Smith-Simmer, Lauren G. Banaszak, Kyle N. Shoger, Erica F. Reinig, Madilynn Peterson, Peter Nicholas, Amanda J. Walne, Inderjeet Dokal, Justin P. Rosenheck, Karolyn A. Oetjen, Daniel C. Link, Andrew E. Gelman, Christopher R. Reilly, Ritika Dutta, R. Coleman Lindsley, Karyn J. Brundige, Suneet Agarwal, Alison A. Bertuch, Jane E. Churpek, Laneshia K. Tague, F. Brad Johnson, Timothy S. Olson, and Daria V. Babushok
Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation
Chengjie Gao, Yitian Dai, Paul A. Spezza, Paul Boasiako, Alice Tang, Giselle Rasquinha, Hui Zhong, Bojing Shao, Yunfeng Liu, Patricia A. Shi, Cheryl A. Lobo, Xiuli An, Anqi Guo, William B. Mitchell, Deepa Manwani, Karina Yazdanbakhsh, and Avital Mendelson

Immunology

A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma
Heejae Kang, Lisa M. Maurer, Jing Cheng, Mei Smyers, Linda R. Klei, Dong Hu, Juliana Hofstatter Azambuja, Marcelo J. Murai, Ahmed Mady, Ejaz Ahmad, Matthew Trotta, Hanna B. Klei, Minda Liu, Prasanna Ekambaram, Zaneta Nikolovska-Coleska, Bill B. Chen, Linda M. McAllister-Lucas, and Peter C. Lucas
Asparagine drives immune evasion in bladder cancer via RIG-I stability and type I IFN signaling
Wenjie Wei, Hongzhao Li, Shuo Tian, Chi Zhang, Junxiao Liu, Wen Tao, Tianwei Cai, Yuhao Dong, Chuang Wang, Dingyi Lu, Yakun Ai, Wanlin Zhang, Hanfeng Wang, Kan Liu, Yang Fan, Yu Gao, Qingbo Huang, Xin Ma, Baojun Wang, Xu Zhang, and Yan Huang
SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria
Joaquín Miguel Pellegrini, Anne Keriel, Laurent Gorvel, Sean Hanniffy, Vilma Arce-Gorvel, Mile Bosilkovski, Javier Solera, Stéphane Méresse, Sylvie Mémet, and Jean-Pierre Gorvel
Virus-associated inflammation imprints an inflammatory profile on monocyte-derived macrophages in the human liver
Juan Diego Sanchez Vasquez, Shirin Nkongolo, Daniel Traum, Valentin Sotov, Samuel C. Kim, Deeqa Mahamed, Aman Mehrotra, Anjali Patel, Diana Y. Chen, Scott Fung, Anuj Gaggar, Jordan J. Feld, Kyong-Mi Chang, Jeffrey J. Wallin, Ben X. Wang, Harry L.A. Janssen, and Adam J. Gehring

Infectious disease

Clinical Research and Public Health
CRISPR-mediated detection of Pneumocystis transcripts in bronchoalveolar, oropharyngeal, and serum specimens for Pneumocystis pneumonia diagnosis
Brady M. Youngquist, Ayanda Trevor Mnguni, Dora Pungan, Rachel PJ Lai, Guixiang Dai, Chun Fai Ng, Amy Samson, Yasmean Abdelgaliel, Christopher J. Lyon, Bo Ning, Shahid Husain, Sean Wasserman, Jay K. Kolls, and Tony Y. Hu

Inflammation

Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis
Takashi Suzuki, Erik Loyde, Sara Chen, Valerie Etzrodt, Temitayo O. Idowu, Amanda J. Clark, Marie Christelle Saade, Brenda Mendoza Flores, Shulin Lu, Gabriel Birrane, Vamsidhara Vemireddy, Benjamin Seeliger, Sascha David, and Samir M. Parikh

Metabolism

Cell-intrinsic insulin signaling defects in human iPS cell–derived hepatocytes in type 2 diabetes
Arijeet K. Gattu, Maria Tanzer, Tomer M. Yaron-Barir, Jared L. Johnson, Ashok Kumar Jayavelu, Hui Pan, Jonathan M. Dreyfuss, Lewis C. Cantley, Matthias Mann, and C. Ronald Kahn

Neuroscience

Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models
Minkyung Kang, Jihye Choi, Jeongho Han, Toshiyuki Araki, Soo-Whee Kim, Hyun-Hee Ryu, Min-Gyun Kim, Seoyeon Kim, Hanbyul Jang, Sun Yong Kim, Kyoung-Doo Hwang, Soobin Kim, Myeongjong Yoo, Jaegeon Lee, Kitae Kim, Pojeong Park, Ja Eun Choi, Dae Hee Han, Yujin Kim, Jeongyeon Kim, Sunghoe Chang, Bong-Kiun Kaang, Jung Min Ko, Keun-Ah Cheon, Joon-Yong An, Sang Jeong Kim, Hyungju Park, Benjamin G. Neel, Chul Hoon Kim, and Yong-Seok Lee

Oncology

Off-the-shelf invariant NKT cells expressing anti-PSCA CAR and IL-15 promote pancreatic cancer regression in mice
Zhenyu Dai, Zheng Zhu, Zhiyao Li, Lei Tian, Kun-Yu Teng, Hanyu Chen, Li-Shu Wang, Jianying Zhang, Laleh Melstrom, Michael A. Caligiuri, and Jianhua Yu
Rachel Elizabeth Ann Fincham, Joe Poh Sheng Yeong, and Hemant Mahendrakumar Kocher
Super-enhancer–driven EFNA1 fuels tumor progression in cervical cancer via the FOSL2-Src/AKT/STAT3 axis
Shu-Qiang Liu, Xi-Xi Cheng, Shuai He, Tao Xia, Yi-Qi Li, Wan Peng, Ya-Qing Zhou, Zi-Hao Xu, Mi-Si He, Yang Liu, Pan-Pan Wei, Song-Hua Yuan, Chang Liu, Shu-Lan Sun, Dong-Ling Zou, Min Zheng, Chun-Yan Lan, Chun-Ling Luo, and Jin-Xin Bei
Identification of potent biparatopic antibodies targeting FGFR2 fusion–driven cholangiocarcinoma
Saireudee Chaturantabut, Sydney Oliver, Dennie T. Frederick, Jiwan J. Kim, Foxy P. Robinson, Alessandro Sinopoli, Tian-Yu Song, Yao He, Yuan-Chen Chang, Diego J. Rodriguez, Liang Chang, Devishi Kesar, Meilani Ching, Ruvimbo Dzvurumi, Adel Atari, Yuen-Yi Tseng, Nabeel Bardeesy, and William R. Sellers
Clinical Research and Public Health
A multicenter prospective clinical trial reveals cell-free DNA methylation markers for early esophageal cancer
Ruixiang Zhang, Yongzhan Nie, Xiaobing Chen, Tao Jiang, Jinhai Wang, Yuhui Peng, Guangpeng Zhou, Yong Li, Lina Zhao, Beibei Chen, Yunfeng Ni, Yan Cheng, Yiwei Xu, Zhenyu Zhu, Xianchun Gao, Zhen Wu, Tianbao Li, Jie Zhao, Cantong Liu, Gang Zhao, Jiakuan Chen, Jing Zhao, Gang Ji, Xiaoliang Han, Jie He, and Yin Li
LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models
Alice E. Shin, Kensuke Sugiura, Secunda W. Kariuki, David A. Cohen, Samuel P. Flashner, Andres J. Klein-Szanto, Noriyuki Nishiwaki, Dechokyab De, Neil Vasan, Joel T. Gabre, Christopher J. Lengner, Peter A. Sims, and Anil K. Rustgi
5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis
Kaiyuan Liu, Yingchao Zhang, Genyu Du, Xinyu Chen, Lingling Xiao, Luyao Jiang, Na Jing, Penghui Xu, Chaoxian Zhao, Yiyun Liu, Huifang Zhao, Yujiao Sun, Jinming Wang, Chaping Cheng, Deng Wang, Jiahua Pan, Wei Xue, Pengcheng Zhang, Zhi-Gang Zhang, Wei-Qiang Gao, Shu-Heng Jiang, Kai Zhang, and Helen He Zhu

Virology

PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus
Ying Li, Huihui Ma, Yongjian Zhang, Tinghui He, Binyang Li, Haoran Ren, Jia Feng, Jie Sheng, Kai Li, Yu Qian, Yunfeng Wang, Haoran Zhao, Jie He, Huicheng Li, Hongjin Wu, Yuanfei Yao, and Ming Shi
Corrigendum
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STK4 regulates TLR pathways and protects against chronic inflammation–related hepatocellular carcinoma
Weiyun Li, Jun Xiao, Xin Zhou, Ming Xu, Chaobo Hu, Xiaoyan Xu, Yao Lu, Chang Liu, Shengjie Xue, Lei Nie, Haibin Zhang, Zhiqi Li, Yanbo Zhang, Fu Ji, Lijian Hui, Wufan Tao, Bin Wei, and Hongyan Wang
CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders
Xiuying Bai, Dengshun Miao, Sophia Xiao, Dinghong Qiu, René St-Arnaud, Martin Petkovich, Ajay Gupta, David Goltzman, and Andrew C. Karaplis

In-Press Previews

Published April 1, 2025, at 12:00 PM EDT
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Research
Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
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Cxcr3 promotes protection from colorectal cancer liver metastasis by driving NK cell infiltration and plasticity
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Published April 3, 2025, at 12:00 PM EDT
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Clinical Research and Public Health
Safety and implementation of phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns
Avy Violari, Kennedy Otwombe, William Hahn, Shiyu Chen, Deirdre Josipovic, Vuyelwa Baba, Asimenia Angelidou, Kinga K. Smolen, Ofer Levy, Nonhlanhla N. Mkhize, Amanda S. Woodward Davis, Troy M. Martin, Barton F. Haynes, Wilton B. Williams, Zachary K. Sagawa, James G. Kublin, Laura Polakowski, Margaret Brewinski Isaacs, Catherine Yen, Georgia Tomaras, Lawrence Corey, Holly Janes, Glenda E. Gray
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SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction
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Gut microbial metabolite 4-hydroxybenzeneacetic acid drives colorectal cancer progression via accumulation of immunosuppressive PMN-MDSCs
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Research Letter
Immune repertoire profiling uncovers pervasive T-cell clonal expansions in benign prostatic hyperplasia
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Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells
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Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice
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Published April 7, 2025
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Unveiling mechanisms underlying kidney function changes during sex hormone therapy
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Published April 8, 2025, at 12:00 PM EDT
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Identification of CD84 as a potent survival factor in acute myeloid leukemia
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Complement pathway activation mediates pancreatic cancer-induced muscle wasting and pathological remodeling
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Preadipocyte IL-13/IL-13Rα1 signaling regulates beige adipogenesis through modulation of PPARγ activity
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Alternative splicing of uromodulin enhances mitochondrial metabolism for adaptation to stress in kidney epithelial cells
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Published April 15, 2025, at 12:00 PM EDT
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Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex
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Targeting melanocortin 4 receptor to treat sleep disordered breathing in mice
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The Journal of Clinical Investigation
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