Review
Immunology
Jiaxuan Chen, Shuzhen Liao, Zengzhi Xiao, Quanren Pan, Xi Wang, Kangyuan Shen, Shuting Wang, Lawei Yang, Fengbiao Guo, Hua-feng Liu, Qingjun Pan
Summary: Animal models are essential for studying human diseases, but they do not fully replicate the complex internal environment of humans. Immunodeficient mice, lacking certain genes and cell populations, allow the establishment of humanized mouse models that simulate the human immune system. These models are widely used in disease research but face challenges that need to be addressed for further improvement.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Naomi Kawashima, Yuichi Ishikawa, Jeong Hui Kim, Yoko Ushijima, Akimi Akashi, Yohei Yamaguchi, Hikaru Hattori, Marie Nakashima, Seara Ikeno, Rika Kihara, Takahiro Nishiyama, Takanobu Morishita, Koichi Watamoto, Yukiyasu Ozawa, Kunio Kitamura, Hitoshi Kiyoi
Summary: The clonal dynamics and selection mechanisms in patient-derived xenografts (PDX) of acute myeloid leukemia (AML) are not fully understood. In this study, the authors generated 160 AML-PDX models to track the clonal dynamics of primary and relapsed AML, finding selectively enriched subclones associated with therapy resistance.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jiwon Yang, Jing Jiao, Kyle M. Draheim, Guoxiang Yang, Hongyuan Yang, Li-Chin Yao, Leonard D. Shultz, Dale L. Greiner, Deepa Rajagopal, Sandrine Vessillier, Curtis C. Maier, Sunish Mohanan, Danying Cai, Mingshan Cheng, Michael A. Brehm, James G. Keck
Summary: Immuno-oncology (IO)-based therapies have been successful in treating cancer, but may lead to severe adverse events like cytokine release syndrome (CRS). Currently, there is a lack of in vivo models to evaluate dose-response relationships and safety issues. This study tested an in vivo PBMC humanized mouse model using a specific T-cell engager (BiTE) to assess treatment efficacy and cytokine release. The results show that this model accurately predicts tumor control and cytokine release, and captures variability among donors. The PBMC humanized mouse model is a reliable platform to identify effective treatments and complications.
Article
Biochemistry & Molecular Biology
Xinning Wang, Chengwei Wu, Hong Wei
Summary: The commensal microbiome plays a significant role in cancer immunotherapy, highlighting the need for advanced animal models to support translational research in this field. Recent animal experiments have revealed the correlation between gut microbiota and the host's response to immunotherapy. However, the use of conventional murine models in immunotherapy-associated microbiome research may be unreliable, emphasizing the importance of utilizing more advanced models to study cancer immunotherapy.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Monika Bialecka, Joaquin Montilla-Rojo, Bernard A. J. Roelen, Ad J. Gillis, Leendert H. J. Looijenga, Daniela. C. F. Salvatori
Summary: This study compared tumour development in humanized immune system (HIS) mice and immunocompromised mice (NSG) after injection of cell lines, revealing that the HIS mouse model is comparable to, but not more sensitive than, the NSG immunodeficient model for studying the malignancy of stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Yaru Wang, Zhenzhen Zhang, Bin Liu, Chunzhi Zhang, Junying Zhao, Xianping Li, Lijun Chen
Summary: The gestational intestinal microbiota can colonize the intestines of mice, allowing for the construction of a humanized mouse model of gestational FMT. However, the transplantation outcomes are influenced by the background flora and timing.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Oncology
Morgane M. Cogels, Redouane Rouas, Ghanem E. Ghanem, Philippe Martinive, Ahmad Awada, Dirk Van Gestel, Mohammad Krayem
Summary: Immunotherapy with checkpoint inhibitors has revolutionized cancer treatment, but clinical trials face challenges, leading to the importance of humanized mouse models for preclinical research to better understand treatment mechanisms and select optimal regimens. These models also hold potential for advancing research on radiation therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Minghui Fang, Jun Zou, Fei Xu, Xue Wang, Shucheng Hua, Qi Zhou, Yong-guang Yang, Zheng Hu
Summary: The development of an animal model to study immune responses to pig vessels is crucial for improving immunosuppressive strategies in clinical pig organ transplantation.
XENOTRANSPLANTATION
(2023)
Article
Neurosciences
Yuko Ogawa, Emi Tanaka, Yoshiaki Sato, Masahiro Tsuji
Summary: SCID mice can serve as an appropriate preclinical model for cell therapies for neonatal HIE, showing comparable severity of brain damage and hypothermia effects to wild-type mice.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Shulian Tan, Minghui Fang, Wei Fan, Zhaowei Wang, Yanan Lv, Jun Zou, Xue Wang, Bin Liu, Yong-Guang Yang, Zheng Hu
Summary: Researchers have successfully achieved long-term production of human cytokines in immunodeficient mice using a transposon-plasmid-based hydrodynamic injection approach. This method can promote the reconstitution of human immune function in mice.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Hematology
Stephanie A. Renna, James Michael, Xianguo Kong, Lin Ma, Peisong Ma, Marvin T. Nieman, Leonard C. Edelstein, Steven E. McKenzie
Summary: The study found functional differences between human and mouse PAR4, including responsiveness and signaling pathways, highlighting the importance of considering these differences when interpreting mouse PAR4 studies.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Rosa Nguyen, Anand G. Patel, Lyra M. Griffiths, Jason Dapper, Elizabeth A. Stewart, Jim Houston, Melissa Johnson, Walter J. Akers, Wayne L. Furman, Michael A. Dyer
Summary: Faithful tumor mouse models are essential research tools for advancing the field of immuno-oncology, especially in diseases with low incidence like pediatric malignancies. Current conventional mouse models fail to replicate the tumor heterogeneity and microenvironment complexity of human pathology.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Josef Skoda, Klara Dohnalova, Karel Chalupsky, Aaron Stahl, Markus Templin, Jana Maixnerova, Stanislav Micuda, Lars Grontved, Albert Braeuning, Petr Pavek
Summary: This study found that TCPOBOP disrupts lipid metabolism in humanized CAR mice and has divergent effects compared to the prototypical CAR-mediated response in WT mice. This suggests the need for appropriate model ligands and humanized animal models when testing endocrine disruption and characterizing adverse outcome pathways.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Microbiology
Christina L. Hutson, Ashley Kondas, Jana M. Ritter, Zachary Reed, Sharon Dietz Ostergaard, Clint N. Morgan, Nadia Gallardo-Romero, Cassandra Tansey, Matthew R. Mauldin, Johanna S. Salzer, Christine M. Hughes, Cynthia S. Goldsmith, Darin Carroll, Victoria A. Olson
Summary: Research has found that three humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model. Following a VARV challenge mimicking human smallpox transmission, the virus spread systemically within the humanized mice similar to the course of human smallpox, facilitating testing of medical countermeasures.
Article
Microbiology
Hernando Gutierrez-Barbosa, Sandra Medina-Moreno, Federico Perdomo-Celis, Harry Davis, Carolina Coronel-Ruiz, Juan C. Zapata, Joel V. Chua
Summary: Humanized mice are valuable for studying human diseases, but it is important to understand their strengths and limitations and choose the appropriate model. This study found that the Hu-SGM3 model consistently produced higher numbers of various human immune cells, while the hu-NOG-EXL model had a higher number of circulating platelets in an inactivated state. The hu-NSG and hu-NCG models had low frequencies of immune cells. Therefore, selecting the right humanized mouse model is crucial for specific research questions.
Article
Multidisciplinary Sciences
Yuanbin Song, Anthony Rongvaux, Ashley Taylor, Tingting Jiang, Toma Tabaldi, Kunthavai Balasubramanian, Arun Bagale, Yunus Kasim Terzi, Rana Gbyli, Xiaman Wang, Xiaoying Fu, Yimeng Gao, Jun Zhao, Nikolai Podoltsev, Mina Xu, Natalia Neparidze, Ellice Wong, Richard Torres, Emanuela M. Bruscia, Yuval Kluger, Markus G. Manz, Richard A. Flavell, Stephanie Halene
NATURE COMMUNICATIONS
(2019)
Article
Hematology
Juliana Xavier-Ferrucio, Vanessa Scanlon, Xiuqi Li, Ping-Xia Zhang, Larisa Lozovatsky, Nadia Ayala-Lopez, Toma Tebaldi, Stephanie Halene, Chang Cao, Mark D. Fleming, Karin E. Finberg, Diane S. Krause
Article
Biochemical Research Methods
Yongdeng Zhang, Lena K. Schroeder, Mark D. Lessard, Phylicia Kidd, Jeeyun Chung, Yuanbin Song, Lorena Benedetti, Yiming Li, Jonas Ries, Jonathan B. Grimm, Luke D. Lavis, Pietro De Camilli, James E. Rothman, David Baddeley, Joerg Bewersdorf
Article
Immunology
Yimeng Gao, Radovan Vasic, Yuanbin Song, Rhea Teng, Chengyang Liu, Rana Gbyli, Giulia Biancon, Raman Nelakanti, Kirsten Lobben, Eriko Kudo, Wei Liu, Anastasia Ardasheva, Xiaoying Fu, Xiaman Wang, Poorval Joshi, Veronica Lee, Burak Dura, Gabriella Viero, Akiko Iwasaki, Rong Fan, Andrew Xiao, Richard A. Flavell, Hua-Bing Li, Toma Tebaldi, Stephanie Halene
Article
Multidisciplinary Sciences
Yuanbin Song, Liang Shan, Rana Gbyli, Wei Liu, Till Strowig, Amisha Patel, Xiaoying Fu, Xiaman Wang, Mina L. Xu, Yimeng Gao, Ashley Qin, Emanuela M. Bruscia, Toma Tebaldi, Giulia Biancon, Padmavathi Mamillapalli, David Urbonas, Elizabeth Eynon, David G. Gonzalez, Jie Chen, Diane S. Krause, Jonathan Alderman, Stephanie Halene, Richard A. Flavell
Summary: This immunodeficient murine model with combined human liver and cytokine humanization enhances human erythropoiesis and RBC survival in circulation. It can be used to study diseases affecting RBCs and replicate acute sickle cell disease pathology.
Article
Pharmacology & Pharmacy
Haiyan Liu, Ziping Li, Fei Qiu, Chunjie Li, Xiaojing Lin, Yingyi He, Maoxiang Qian, Yuanbin Song, Hui Zhang
Summary: This study investigated the association between NR3C1 gene mutations and treatment outcomes in pediatric acute lymphoblastic leukemia (ALL), finding that NR3C1 mutations are associated with glucocorticoid resistance. Loss-of-function (LoF) NR3C1 mutations influence GC resistance, indicating that NR3C1 alterations play a critical role in GC resistance and may contribute to treatment failure and relapse in ALL.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Esen Sefik, Benjamin Israelow, Haris Mirza, Jun Zhao, Rihao Qu, Eleanna Kaffe, Eric Song, Stephanie Halene, Eric Meffre, Yuval Kluger, Michel Nussenzweig, Craig B. Wilen, Akiko Iwasaki, Richard A. Flavell
Summary: This study introduces a humanized mouse model of COVID-19 that replicates the immune response and pathological features of the infection, providing a valuable tool for investigating disease mechanisms and treatment options.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Jiabi Qian, Zifeng Li, Kunlin Pei, Ziping Li, Chunjie Li, Muxia Yan, Maoxiang Qian, Yuanbin Song, Hui Zhang, Yingyi He
Summary: Through targeted sequencing and high-throughput drug screening, we studied the role of RAS mutations in ALL patients and found that RAS mutations were associated with a higher relapse incidence in children with ALL. Among these mutations, NRAS mutations had a higher leukemogenic potential and might exhibit different responsiveness to inhibition of multiple signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Rana Gbyli, Yuanbin Song, Wei Liu, Yimeng Gao, Giulia Biancon, Namrata S. Chandhok, Xiaman Wang, Xiaoying Fu, Amisha Patel, Ranjini Sundaram, Toma Tebaldi, Padmavathi Mamillapalli, Amer M. Zeidan, Richard A. Flavell, Thomas Prebet, Ranjit S. Bindra, Stephanie Halene
Summary: Treatment options for relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients are limited. Our study demonstrates the effectiveness of the PARP inhibitor olaparib in IDH1/2-mutant AML/MDS patients, particularly those who are resistant to IDH(m)i treatment or have relapsed.
Article
Biochemistry & Molecular Biology
Giulia Biancon, Poorval Joshi, Joshua T. Zimmer, Torben Hunck, Yimeng Gao, Mark D. Lessard, Edward Courchaine, Andrew E. S. Barentine, Martin Machyna, Valentina Botti, Ashley Qin, Rana Gbyli, Amisha Patel, Yuanbin Song, Lea Kiefer, Gabriella Viero, Nils Neuenkirchen, Haifan Lin, Joerg Bewersdorf, Matthew D. Simon, Karla M. Neugebauer, Toma Tebaldi, Stephanie Halene
Summary: Splicing factor mutations, especially in U2AF1, are common drivers of myeloid malignancies, affecting the splicing process and leading to intron retention and exon exclusion. In addition, U2AF1 mutations directly influence the components of stress granules, which are involved in adaptive oncogenic strategies in cancer cells.
Letter
Oncology
Amer M. Zeidan, Jan Philipp Bewersdorf, Vanessa Hasle, Rory M. Shallis, Ethan Thompson, Daniel Lopes de Menezes, Shelonidta Rose, Isaac Boss, Stephanie Halene, Torsten Haferlach, Brian Fox
Article
Biochemical Research Methods
Giulia Biancon, Emma Busarello, Poorval Joshi, Bluma J. Lesch, Stephanie Halene, Toma Tebaldi
Summary: This study presents experimental and computational analysis pipelines of fractionated eCLIP-seq (freCLIP-seq), allowing transcriptome-wide analysis of protein-RNA interactions at single-nucleotide level with increased resolution.
Article
Biochemical Research Methods
Yimeng Gao, Shirui Chen, Stephanie Halene, Toma Tebaldi
Summary: The presence of dsRNAs in cells plays multiple regulatory functions, with viral dsRNAs activating innate immune responses. Alterations in RNA editing and modifications can lead to accumulation of abnormal endogenous dsRNAs and trigger harmful innate immune responses. This study provides a complete protocol for measuring dsRNAs in live mouse tissue using dsRNA immunoprecipitation and sequencing, focusing on tissue isolation, immunoprecipitation, and computational analysis.
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)
