Article
Biology
Robert M. Gingras, Abigail M. Sulpizio, Joelle Park, Anthony Bretscher, Benjamin S. Glick
Summary: This study defined the order and behavior characteristics of critical components in the late secretion process from the Golgi to the plasma membrane in yeast, revealing an ordered and robust series of events that provide insights into the function of the Sec4 protein and effector exchange.
Article
Chemistry, Multidisciplinary
Shiyi Wei, Fei Wu, Jing Liu, Wenliang Ji, Xiulan He, Ran Liu, Ping Yu, Lanqun Mao
Summary: This study provides the first direct evidence of neurotoxicity induced by nanoplastics, using single-vesicle electrochemistry. The researchers observed cellular uptake of polystyrene nanoplastics, leading to cell viability loss and reductions in vesicular catecholamine content, exocytotic activity, neurotransmitter release, and fusion pore opening-closing speed. Mechanistic investigations suggest that nanoplastics disrupt F-actin assemblies. This research offers important insights into how nanoplastics affect neurotransmitter secretion and neural functions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Nanoscience & Nanotechnology
Jiapei Yang, Li Xu, Ling Di, Yue Su, Xinyuan Zhu
Summary: PEG, as the gold standard for stealth polymer materials, is widely used in drug delivery due to its excellent properties. However, the lack of understanding about the fate of PEG at the cellular level has hindered its application in diagnosis and therapy. Research showed that PEG could be internalized into cells in 1 hour, localized to lysosomes, cytosol, ER, and mitochondria. The fate of PEG in cells could be regulated by conjugating different small molecules, which is crucial for the rational design of PEGylation for drug delivery.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Plant Sciences
Martiniano Maria Ricardi, Niklas Wallmeroth, Cecilia Cermesoni, Dietmar Gerald Mehlhorn, Sandra Richter, Lei Zhang, Josephine Mittendorf, Ingeborg Godehardt, Kenneth Wayne Berendzen, Edda von Roepenack-Lahaye, York-Dieter Stierhof, Volker Lipka, Gerd Juergens, Christopher Grefen
Summary: The final step in secretion is membrane fusion facilitated by SNARE proteins that reside in opposite membranes. The formation of a trans-SNARE complex between one R and three Q coiled-coiled SNARE domains drives the final approach of the membranes providing the mechanical energy for fusion. Biological control of this mechanism is exerted by additional domains within some SNAREs.
Review
Plant Sciences
Xiaobo Zhu, Junjie Yin, Hongming Guo, Yuping Wang, Bingtian Ma
Summary: The vesicle trafficking apparatus is crucial for maintaining the homeostasis of membrane-enclosed organelles in eukaryotic cells. Research on vesicle trafficking in plants, particularly rice, is limited, and further investigations are needed to uncover the mysteries of this system.
FRONTIERS IN PLANT SCIENCE
(2023)
Review
Cell Biology
I. -Ying Kuo, Chih-Hsiung Hsieh, Wan-Ting Kuo, Chih-Peng Chang, Yi-Ching Wang
Summary: Cells in the tumor microenvironment require a class of checkpoints to regulate various secretion and transport processes. Recent studies have shown that Rab proteins mediate communication between diverse cargoes and substrates through vesicular trafficking and secretion pathways in the tumor microenvironment. This review focuses on the role and regulation of vesicular secretion pathways in the tumor microenvironment, and describes the latest research advances and future directions.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yongtian Chen, Jing Kang, Ru Zhen, Liyang Zhang, Caiyong Chen
Summary: Vesicle trafficking is a critical cellular process in eukaryotes, and this study identifies CCT4 as a key regulator of protein secretion and vesicle trafficking. The deficiency of CCT4 impairs the trafficking of endocytic markers in intestinal cells, and silencing CCT4 in human cells leads to defective endosomal trafficking. These findings highlight the essential role of CCT in regulating vesicle trafficking and provide new insights into its cellular function.
Article
Biochemistry & Molecular Biology
Zuodong Ye, Dawei Wang, Yingying Lu, Yunjiao He, Jingting Yu, Wenjie Wei, Chang Chen, Rui Wang, Liang Zhang, Liangren Zhang, Minh T. N. Le, William C. Cho, Mengsu Yang, Hongmin Zhang, Jianbo Yue
Summary: V1 shows significant anti-metastatic activity by inhibiting cancer cell migration and metastasis in vitro and in vivo, as well as suppressing colony formation, migration, and invasion of cancer cells. V1 targets CapZ beta to inhibit endosomal trafficking and metastasis processes.
Article
Neurosciences
Che-Wei Chang, Yu-Tien Hsiao, Meyer B. Jackson
Summary: This study demonstrates that Synaptophysin (Syp) and synaptogyrin (Syg) play a regulatory role in dense-core vesicle function at various stages, affecting fusion initiation, mode selection between full fusion and kiss-and-run, and influencing the dynamics of both initial and late-stage fusion pores. The transmembrane domain (TMD) of Syp influences small initial fusion pores, while the C-terminal domain influences large late-stage fusion pores, possibly through an interaction with dynamin.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Jennifer L. Johnson, Elsa Meneses-Salas, Mahalakshmi Ramadass, Jlenia Monfregola, Farhana Rahman, Raquel Carvalho Gontijo, William B. Kiosses, Kersi Pestonjamasp, Dale Allen, Jinzhong Zhang, Douglas G. Osborne, Yanfang Peipei Zhu, Nathan Wineinger, Kasra Askari, Danni Chen, Juan Yu, Scott C. Henderson, Catherine C. Hedrick, Matilde Valeria Ursini, Sergio Grinstein, Daniel D. Billadeau, Sergio D. Catz
Summary: This study investigates the process of exocytosis in neutrophil leukocytes and shows that the actin nucleator protein WASH plays a critical role in this process. The authors find that WASH facilitates the release of gelatinase granules while inhibiting the release of pro-inflammatory granules. They also discover that a deficiency in WASH leads to dysregulated secretion and inflammation in neutrophil leukocytes.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Shen Wang, Cong Ma
Summary: This review summarizes the recent advances in understanding the functions and molecular mechanisms of Munc18-1 and Munc13-1 in neuronal SNARE complex assembly. It also discusses the functional similarities and differences between Munc18-1 and Munc13-1 in neurons and their homologs in other intracellular membrane trafficking systems.
Review
Biotechnology & Applied Microbiology
Mauro Torres, Hirra Hussain, Alan J. Dickson
Summary: This review highlights the importance of mammalian cell factories, particularly the CHO cell system, in biopharmaceutical production. It provides an overview of the secretory pathway, the challenges in protein production, and the advancements in engineering CHO cell secretory machinery. The understanding of the mechanisms underlying the unique secretory function of antibody-producing plasma cells offers potential for further improvement in biopharmaceutical manufacturing.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Fan Fan, Yumei Wu, Manami Hara, Adam Rizk, Chen Ji, Dan Nerad, Natalia Tamarina, Xuelin Lou
Summary: This study revealed the crucial role of dynamins in endocytosis and secretion capacity of pancreatic beta cells, indicating that deficiency in dynamin-mediated endocytosis can lead to impaired insulin secretion, increasing the risk of endocrine dysfunction and diabetes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Weiwei Zhang, Christopher J. Staiger
Summary: This study introduces a quantitative approach for measuring the frequency of vesicle tethering events during exocytosis in plant cells. The results demonstrate that the initial vesicle tethering step is dependent on actin and myosin XI, while microtubules do not directly affect vesicle tethering and fusion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Shivani Gupta, Bhavana Shah, Coral Shek Fung, Pik Kay Chan, Devin L. Wakefield, Scott Kuhns, Chetan T. Goudar, James M. Piret
Summary: Since 2015, more than 34 biosimilars have been approved by the FDA, leading to a renewed focus on technology development for therapeutic protein production. The genetic differences between host cell lines used in biologics manufacturing pose a challenge. To address this, a CHO cell line was engineered to produce monoclonal antibodies with murine glycans, aiming to match the reference product expressed in murine cells. This study demonstrates the feasibility of using CHO cells to produce mAbs with murine glycans, potentially reducing uncertainty in biosimilarity development.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Haitang Yang, Sean R. R. Hall, Beibei Sun, Liang Zhao, Yanyun Gao, Ralph A. Schmid, Swee T. Tan, Ren-Wang Peng, Feng Yao
Summary: The study revealed that loss-of-function in the upstream regulator NF2 of the Hippo pathway is associated with aberrant activation of Hippo-YAP-independent signaling, defining distinct MPM subsets with different molecular features and prognosis. This has important clinical implications for precision oncology in MPM patients.
Article
Oncology
Tuo Zhang, Beibei Sun, Chenxi Zhong, Ke Xu, Zhexin Wang, Paul Hofman, Tatsuya Nagano, Antoine Legras, Biagio Ricciuti, Daniel Breadner, Duilio Divisi, Ralph A. Schmid, Ren-Wang Peng, Haitang Yang, Feng Yao
Summary: Ferroptosis inducers show high sensitivity in EGFR mutant lung cancer cells with resistance, while the histone deacetylase inhibitor Vorinostat can enhance the efficacy of ferroptosis inducers.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Zhang Yang, Shun-Qing Liang, Maria Saliakoura, Haitang Yang, Eric Vassella, Georgia Konstantinidou, Mario Tschan, Balazs Hegedus, Liang Zhao, Yanyun Gao, Duo Xu, Haibin Deng, Thomas M. Marti, Gregor J. Kocher, Wenxiang Wang, Ralph A. Schmid, Ren-Wang Peng
Summary: By combining FGFR1 and PLK1 inhibitors, synergistic cytotoxicity can be achieved in KRAS-mutant tumors, inducing cell death. This treatment induces apoptosis by upregulating ROS and activating the JNK/p38 pathway, while enhancing sensitivity of tumor cells to inhibitors by inhibiting autophagy.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Lijuan Ma, Thomas Andrieu, Brett McKinnon, Lea Duempelmann, Ren-Wang Peng, Carlos Wotzkow, Christoph Mueller, Michael D. Mueller
Summary: This study found a negative correlation between low expression of progesterone receptors (PR) and epithelial-to-mesenchymal transition (EMT) in endometriosis lesions. In both in vitro and in vivo experiments, EMT leads to downregulation of PR gene expression by upregulating EMT transcription factors like SNAI1 and SNAI2, potentially resulting in progesterone resistance.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Oncology
Zhang Yang, Shun-Qing Liang, Liang Zhao, Haitang Yang, Thomas M. Marti, Balazs Hegedus, Yanyun Gao, Bin Zheng, Chun Chen, Wenxiang Wang, Patrick Dorn, Gregor J. Kocher, Ralph A. Schmid, Ren-Wang Peng
Summary: This study reveals the metabolic dependency induced by mutant KRAS and identifies nucleolar protein 5A (NOP56) and mTOR as potential targets for the treatment of KRAS-mutant cancers. The depletion of NOP56 leads to synthetic lethal susceptibility to mTOR inhibition due to the regulation of ROS homeostasis. Co-targeting NOP56 and mTOR significantly enhances cell death in KRAS-mutant tumor cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Haitang Yang, Sabina Berezowska, Patrick Dorn, Philipp Zens, Peiru Chen, Ren-Wang Peng, Thomas M. Marti, Gregor J. Kocher, Ralph A. Schmid, Sean R. R. Hall
Summary: This study investigates the relationship between the tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM). The results suggest that targeting the TME can potentially redirect the fate of TILs and restore anti-tumor immunity in MPM.
Review
Oncology
Wenjuan Ning, Zhang Yang, Gregor J. Kocher, Patrick Dorn, Ren-Wang Peng
Summary: KRAS is the most common oncogene in human cancers, with G12C inhibitors providing a breakthrough by covalently targeting the G12C substitution and demonstrating potent clinical efficacy. However, challenges such as drug resistance must be addressed to maximize the efficacy of KRAS(G12C) inhibitor therapy. Combination treatments with other therapeutic agents and an understanding of compensatory signaling pathways are promising strategies to overcome these challenges.
Review
Oncology
Yanyun Gao, Marianna Kruithof-de Julio, Ren-Wang Peng, Patrick Dorn
Summary: Malignant pleural mesothelioma is a deadly cancer with limited treatment options and low survival rates. Patient-derived organoid cultures offer a promising approach for studying the disease, identifying new therapeutic targets, and developing personalized treatments.
Article
Biochemistry & Molecular Biology
Darya Karatkevich, Haibin Deng, Yanyun Gao, Emilio Flint, Ren-Wang Peng, Ralph Alexander Schmid, Patrick Dorn, Thomas Michael Marti
Summary: This study found that prolonged pretreatment with pemetrexed significantly reduces cell growth in malignant pleural mesothelioma (MPM), induces cell cycle arrest, persistent DNA damage accumulation, and a senescence phenotype. Optimizing the treatment schedule by pretreatment with pemetrexed enhances the efficacy of pemetrexed-cisplatin combination therapy and may improve patient outcomes in MPM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Duo Xu, Shengchen Liu, Xi Wu, Thomas M. Marti, Patrick Dorn, Ralph A. Schmid, Ren-Wang Peng, Yongqian Shu
Summary: This study investigates the immunological role of NSD3 in driving lung squamous cell carcinoma (LUSC) and provides therapeutic rationales for NSD3-amplified squamous lung cancer. The findings reveal that NSD3 amplification is associated with a non-inflamed tumor immune microenvironment (TIME) and a worse immunotherapy outcome. The high activity of unfolded protein response (UPR) signaling is identified as a key mediator for the non-immunogenic phenotype of NSD3-amplified LUSC.
Article
Oncology
Haibin Deng, Huixiang Ge, Christelle Dubey, Tereza Losmanova, Michaela Medova, Georgia Konstantinidou, Seyran Mathilde Mutlu, Fabienne Esther Birrer, Tess Melinda Brodie, Deborah Stroka, Wenxiang Wang, Ren-Wang Peng, Patrick Dorn, Thomas Michael Marti
Summary: In this study, we modified the protocol to handle the Cre-induced KP mouse model under BSL-1 conditions by using a commercially available gutless, adeno-associated, Cre-expressing vector instead of a virus-based delivery system. The anesthesia and instillation protocols were optimized, resulting in increased productivity and reduced complications. Longitudinal monitoring of tumor growth was achieved by repeated micro-CT analysis of individual animals, significantly reducing the number of animals required per experiment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Haitang Yang, Wenyan Ma, Beibei Sun, Liwen Fan, Ke Xu, Sean R. R. Hall, Mohammad Faisal Al-Hurani, Ralph A. Schmid, Ren-Wang Peng, Toyoaki Hida, Zhexin Wang, Feng Yao
Summary: The study found that smoking signature is a better predictor of pathological response to immunotherapy compared to PD-L1 expression, possibly due to increased TMB and/or MSI related to smoking exposure. In contrast, CT scan has poor performance in evaluating the response to immunotherapy.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Meeting Abstract
Oncology
R. Peng, R. A. Schmid
JOURNAL OF THORACIC ONCOLOGY
(2021)
Meeting Abstract
Oncology
Z. Yang, S. Liang, R. Peng, R. A. Schmid
JOURNAL OF THORACIC ONCOLOGY
(2021)
Meeting Abstract
Oncology
Y. Gao, H. Yang, H. Deng, D. Karatkevich, R. Peng, R. A. Schmid, T. Marti
JOURNAL OF THORACIC ONCOLOGY
(2021)