Review
Virology
Nicolas M. S. Galvez, Catalina A. Andrade, Gaspar A. Pacheco, Jorge A. Soto, Vicente Stranger, Thomas Rivera, Abel E. Vasquez, Alexis M. Kalergis
Summary: Human metapneumovirus (hMPV) is a major pathogen causing acute respiratory infections in children under 5 years old, leading to a significant health burden. The structural components of hMPV can be detected by host cell receptors, triggering immune responses to clear the infection. Host intrinsic factors can modulate immune responses and inhibit viral replication during hMPV infections.
Article
Multidisciplinary Sciences
Adam Sateriale, Jodi A. Gullicksrud, Julie B. Engiles, Briana McLeod, Emily M. Kugler, Jorge Henao-Mejia, Ting Zhou, Aaron M. Ring, Igor E. Brodsky, Christopher A. Hunter, Boris Striepen
Summary: Cryptosporidium infection causes a significant disease burden in children, with the inflammasome playing a critical role in initiating the early response. Mice lacking core inflammasome components show increased parasite burden, while deletion of caspase-1 solely in enterocytes phenocopies whole-body knockout. Activation of the inflammasome leads to release of IL-18, necessary for controlling parasite infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Jinghui Hu, Zhenxin Guan, Jing Chen
Summary: Solid tumors exhibit low oxygen tension, leading to resistance to various therapies. Developing biomaterials capable of targeted modulation of oxygen levels in tumors is crucial for improving treatment outcomes. Different types of oxygen-modulating biomaterials, including oxygen-carrying, oxygen-generating, oxygen-consuming, and oxygen-circulating materials, show promise in anticancer therapeutics for hypoxic tumor treatment.
Article
Medicine, Research & Experimental
Le Li, Zheng Chao, Un Waikeong, Jun Xiao, Yue Ge, Yanan Wang, Zezhong Xiong, Sheng Ma, Zhihua Wang, Zhiquan Hu, Xing Zeng
Summary: This study proposed a new metabolic classification method for renal cell carcinoma and revealed associations between metabolic profiles and immune infiltration. The subcluster with low metabolic profiles had the worst prognosis, highest invasiveness, enhanced immune infiltration but suppressive immunophenotypes. ACAA2 was identified as a tumor suppressor gene associated with increased immune infiltration and elevated PD-1 expression.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Ziyi Feng, Xin Su, Ting Wang, Shu Guo
Summary: This study identified five novel biomarkers related to MSCs osteogenesis and verified their potential roles in immunoregulation and inflammation through in vitro experiments.
Article
Immunology
Mariko Takahashi, Chan-Wang J. Lio, Anaamika Campeau, Martin Steger, Ferhat Ay, Matthias Mann, David J. Gonzalez, Mohit Jain, Sonia Sharma
Summary: In this study, Sharma and colleagues identified DAPK3 as a positive regulator of the STING-interferon-beta activation pathway, essential for driving tumor-intrinsic innate immunity and tumor immune surveillance. Loss of DAPK3 expression or kinase activity impaired STING activation, reduced infiltration of immune cells, and attenuated the response to cancer chemo-immunotherapy. DAPK3 coordinates post-translational modification of STING and is critical for maintaining STING activation and immune response against tumors.
Review
Biochemistry & Molecular Biology
Mugdha Vijay Patwardhan, Ratha Mahendran
Summary: The tumor microenvironment (TME) consists of various cell types, which work together to help cancer cells evade immune monitoring and survive therapy. Single-cell sequencing has enhanced our understanding of the cell types present in the TME and their role in cancer development. This review focuses on the different cell types in the bladder TME and discusses their impact on immune activation, microenvironment shaping, and the effects of hypertensive drugs and anesthetics on bladder cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Liliana M. Sanmarco, Chun-Cheih Chao, Yu-Chao Wang, Jessica E. Kenison, Zhaorong Li, Joseph M. Rone, Claudia M. Rejano-Gordillo, Carolina M. Polonio, Cristina Gutierrez-Vazquez, Gavin Piester, Agustin Plasencia, Lucinda Li, Federico Giovannoni, Hong-Gyun Lee, Camilo Faust Akl, Michael A. Wheeler, Ivan Mascanfroni, Merja Jaronen, Moneera Alsuwailm, Patrick Hewson, Ada Yeste, Brian M. Andersen, Diana G. Franks, Chien-Jung Huang, Millicent Ekwudo, Emily C. Tjon, Veit Rothhammer, Maisa Takenaka, Kalil Alves de Lima, Mathias Linnerbauer, Lydia Guo, Ruxandra Covacu, Hugo Queva, Pedro Henrique Fonseca-Castro, Maha Al Bladi, Laura M. Cox, Kevin J. Hodgetts, Mark E. Hahn, Alexander Mildner, Joshua Korzenik, Russ Hauser, Scott B. Snapper, Francisco J. Quintana
Summary: Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD). However, the role of environmental factors in IBD susceptibility and severity has been understudied. In this study, an integrated systems approach was used to identify environmental factors and mechanisms that control intestinal inflammation.
Review
Immunology
Zhuoying Tian, Yue Zeng, Yurong Peng, Junqi Liu, Fang Wu
Summary: Activation of the cGAS-STING pathway by cytoplasmic DNA leads to the production of Type-1 interferons, which play a critical role in cancer-immunity cycle. Research has shown that combination therapy of STING agonists has made progress in preclinical and clinical trials, but selecting appropriate combination therapy regimens remains a challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Emily P. Vonderhaar, Nicholas S. Barnekow, Donna McAllister, Laura McOlash, Mahmoud Abu Eid, Matthew J. Riese, Vera L. Tarakanova, Bryon D. Johnson, Michael B. Dwinell
Summary: STING agonists can promote T-cell infiltration, counteract immune suppression, and generate systemic anti-tumor inflammation in locally treated and distant tumors.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Ye Wang, Morvarid Mohseni, Angelo Grauel, Javier Estrada Diez, Wei Guan, Simon Liang, Jiyoung Elizabeth Choi, Minying Pu, Dongshu Chen, Tyler Laszewski, Stephanie Schwartz, Jane Gu, Leandra Mansur, Tyler Burks, Lauren Brodeur, Roberto Velazquez, Steve Kovats, Bhavesh Pant, Giri Buruzula, Emily Deng, Julie T. Chen, Farid Sari-Sarraf, Christina Dornelas, Malini Varadarajan, Haiyan Yu, Chen Liu, Joanne Lim, Huai-Xiang Hao, Xiaomo Jiang, Anthony Malamas, Matthew J. LaMarche, Felipe Correa Geyer, Margaret McLaughlin, Carlotta Costa, Joel Wagner, David Ruddy, Pushpa Jayaraman, Nathaniel D. Kirkpatrick, Pu Zhang, Oleg Iartchouk, Kimberly Aardalen, Viviana Cremasco, Glenn Dranoff, Jeffrey A. Engelman, Serena Silver, Hongyun Wang, William D. Hastings, Silvia Goldoni
Summary: The study unveiled a new immune modulatory function of SHP2, with inhibition promoting anti-tumor immunity by enhancing T cell cytotoxicity and immune-mediated tumor regression. Additionally, SHP2 inhibition improved responses to anti-PD-1 blockade, suggesting its potential as a promising strategy for cancer immunotherapy.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Ryan C. Augustin, Sarah Newman, Aofei Li, Marion Joy, Maureen Lyons, Mary P. Pham, Peter Lucas, Katelyn Smith, Cindy Sander, Brian Isett, Diwakar Davar, Yana G. Najjar, Hassane M. Zarour, John M. Kirkwood, Jason John Luke, Riyue Bao
Summary: In this study, we characterized acral melanoma (AM) and investigated its response to immune checkpoint inhibitors (ICIs). We found differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME) of AM, which may contribute to its poor response to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Optics
Siqi Liang, Jiasheng Zhou, Wenzhao Yang, Sung-Liang Chen
Summary: Photoacoustic microscopy (PAM) is a valuable tool for visualizing optical absorption contrast in vivo. In this study, a low-cost laser diode (LD) was used as the interrogation light source in a non-contact PAM system called PARS-LD. The performance of PARS-LD was comparable to a traditional system using a superluminescent diode (SLD), and in vivo imaging of mouse brain vessels was successfully demonstrated.
Article
Chemistry, Medicinal
Patrik Zeyen, Yanira Zeyn, Daniel Herp, Fereshteh Mahmoudi, Talha Z. Yesiloglu, Frank Erdmann, Matthias Schmidt, Dina Robaa, Christophe Romier, Johannes Ridinger, Corey J. Herbst-Gervasoni, David W. Christianson, Ina Oehme, Manfred Jung, Oliver H. Kraemer, Wolfgang Sippl
Summary: In this study, piperidine-4-acrylhydroxamates were synthesized as potent and highly selective inhibitors of HDAC10. By mimicking the interaction of HDAC10's substrate, the acidic gatekeeper residue Glu274 was successfully targeted. The binding modes of the inhibitors were confirmed through experiments and analysis, and it was demonstrated that 10c and 13b are highly specific HDAC10 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xiaohui Si, Lu Xiao, Christine E. Brown, Dongrui Wang
Summary: This review provides an overview of the development of in vitro and in vivo models for evaluating CAR T cell function, and discusses how these models can provide information for the preclinical assessment of CAR T cell therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ryan D. Chow, Tai Michaels, Stefania Bellone, Tobias M. P. Hartwich, Elena Bonazzoli, Akiko Iwasaki, Eric Song, Alessandro D. Santin
Summary: This study found that patients with mutational MMRd endometrial cancer had higher response rates and longer survival after treatment with the PD-1 inhibitor pembrolizumab compared to those with epigenetic MMRd. However, mutation burden did not correlate with immune checkpoint blockade response. The study also revealed different modes of antitumor immunity between mutational and epigenetic MMRd cancers.
Article
Biotechnology & Applied Microbiology
Xiaoyun Dai, Jonathan J. Park, Yaying Du, Zhenkun Na, Stanley Z. Lam, Ryan D. Chow, Paul A. Renauer, Jianlei Gu, Shan Xin, Zhiyuan Chu, Cun Liao, Paul Clark, Hongyu Zhao, Sarah Slavoff, Sidi Chen
Summary: In this study, a system called CLASH was developed for high-efficiency, high-throughput knock-in engineering. By using Cas12a/Cpf1 mRNA and pooled adeno-associated viruses, CLASH enables simultaneous gene editing and precise transgene knock-in using massively parallel homology-directed repair. The versatility of CLASH makes it applicable to diverse cellular and therapeutic engineering applications. Unbiased selection of CAR-T cells is achieved through massively parallel knock-in engineering.
NATURE BIOTECHNOLOGY
(2023)
Article
Biology
Jonathan J. J. Park, Kyoung A. V. Lee, Stanley Z. Z. Lam, Katherine S. S. Moon, Zhenhao Fang, Sidi Chen
Summary: By analyzing a large-scale dataset of TCR repertoires, we identified signatures associated with COVID-19 disease severity and accurately predicted COVID-19 infection using machine learning models. These analyses provide a systems immunology view of T cell adaptive immune responses to COVID-19.
COMMUNICATIONS BIOLOGY
(2023)
Letter
Oncology
Eric Song, Ryan D. Chow
Article
Biochemistry & Molecular Biology
Emmanuelle M. Ruiz, Solomon A. Alhassan, Youssef Errami, Zakaria Y. Abd Elmageed, Jennifer S. Fang, Guangdi Wang, Margaret A. Brooks, Joe A. Abi-Rached, Emad Kandil, Mourad Zerfaoui
Summary: A 13-gene panel was identified to accurately predict resistance to BRAF/MEK inhibitor therapy in melanoma patients. Dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a treatment-resistant landscape, and HMOX1-mediated mitochondrial stress response was identified as a potential key driver of resistance. These findings highlight the importance of these genes in predicting treatment outcomes and targeting underlying mechanisms to reduce resistance development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Paul Renauer, Jonathan J. Park, Meizhu Bai, Arianny Acosta, Won-Ho Lee, Guang Han Lin, Yueqi Zhang, Xiaoyun Dai, Guangchuan Wang, Youssef Errami, Terence Wu, Paul Clark, Lupeng Ye, Quanjun Yang, Sidi Chen
Summary: Immune evasion is a major obstacle in T cell-based immunotherapies for cancer. This study investigated the possibility of genetically reprogramming T cells to overcome tumor-induced suppression of T-cell function through metabolic reprogramming. The overexpression of ADA and PDK1 enhanced the cytolytic activity of CAR T cells against leukemia cells, while deficiency of ADA or PDK1 dampened this effect. ADA overexpression improved cancer cytolysis under high concentrations of adenosine in the tumor microenvironment. These findings provide insight into metabolic reprogramming in CAR T cells and reveal potential targets for improving CAR T-cell therapy.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Multidisciplinary Sciences
Felix Radford, Jesse Rinehart, Farren J. Isaacs
Summary: This study develops a method to map the nucleotides in the peptidyl transfer center and the resulting epistatic interactions.
Article
Medicine, Research & Experimental
Lydie Naule, Alessandra Mancini, Sidney A. Pereira, Brandon M. Gassaway, John R. Lydeard, John C. Magnotto, Han Kyeol Kim, Joy Liang, Cynara Matos, Steven P. Gygi, Florian T. . Merkle, Rona S. Carroll, Ana Paula Abreu, Ursula B. Kaiser
Summary: MKRN3 acts as an inhibitor of puberty initiation and its deletion leads to significant changes in gene expression related to hypothalamic development and plasticity. Additionally, MKRN3 deletion results in early puberty onset and increased dendritic spine numbers in the arcuate nucleus. NKB and IGF2BP1 are identified as targets of MKRN3 regulation.
Article
Oncology
Ryan D. Chow, Jessica B. Long, Sirad Hassan, Stephanie B. Wheeler, Lisa P. Spees, Michael S. Leapman, Michael E. Hurwitz, Hannah D. McManus, Cary P. Gross, Michaela A. Dinan
Summary: Disparities in the utilization of metastatic renal cell carcinoma systemic therapies were observed among US Medicare beneficiaries from 2015 to 2019, with non-Hispanic Black race and ethnicity and female sex associated with reduced receipt of oral anticancer agents and immunotherapies. These findings highlight the persistence of disparities in mRCC outcomes despite advancements in treatment options.
JNCI CANCER SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Kyle Mohler, Jack M. Moen, Svetlana Rogulina, Jesse Rinehart
Summary: In the past two decades, synthetic biological systems have revolutionized the study of cellular physiology. The use of orthogonal translation systems (OTSs) to incorporate non-standard amino acids has provided unprecedented access to cellular mechanisms regulated by post-translational modifications. However, the systems-level biology of OTS development and utilization remains underexplored. This study investigates the global interactions between OTS components and the cellular environment, aiming to improve OTS performance and enhance orthogonality.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Immunology
Xiaoyu Zhou, Hanbing Cao, Shao-Yu Fang, Ryan D. Chow, Kaiyuan Tang, Medha Majety, Meizhu Bai, Matthew B. Dong, Paul A. Renauer, Xingbo Shang, Kazushi Suzuki, Andre Levchenko, Sidi Chen
Summary: By fusing the CTLA-4 cytoplasmic tail to a CAR, this study enhances the functionality of CAR-T cells and improves their therapeutic efficacy.
Article
Biochemistry & Molecular Biology
Ping Ren, Lei Peng, Luojia Yang, Kazushi Suzuki, Zhenhao Fang, Paul A. Renauer, Qianqian Lin, Meizhu Bai, Tongqing Li, Paul Clark, Daryl Klein, Sidi Chen
Summary: As a clinical vaccine, lipid nanoparticle (LNP) mRNA has shown strong antibody responses and potential for antibody discovery. A strategy called RAMIHM, which combines rapid mRNA immunization of humanized mice with single B cell sequencing (scBCR-seq), was developed to efficiently generate fully human monoclonal antibodies. RAMIHM was used to immunize humanized transgenic mice and successfully generated highly specific antibodies against antigens. This strategy was also extended to cancer immunotherapy targets, demonstrating its broad applicability in antibody development.
CELL CHEMICAL BIOLOGY
(2023)
