The Janus kinase-signal transducer and activator of transcription(JAK-STAT)pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus.It plays a pivotal role in physiologica...The Janus kinase-signal transducer and activator of transcription(JAK-STAT)pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus.It plays a pivotal role in physiological functions,such as hematopoiesis,immune balance,tissue homeostasis,and surveillance against tumors.Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies,autoimmune diseases,hematologic disorders,and cancer.Due to its critical role in maintaining human health and involvement in disease,extensive studies have been conducted on this pathway,ranging from basic research to medical applications.Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level,laying the groundwork for therapeutic development targeting this pathway.Various strategies have been developed to restore its normal function,with promising therapeutic potential.Enhanced comprehension of these molecular mechanisms,combined with advances in protein engineering methodologies,has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications,thereby enhancing their efficiency and safety.In this review,we outline the structural basis that governs key nodes in this pathway,offering a comprehensive overview of the signal transduction process.Furthermore,we explore recent advances in cytokine engineering for therapeutic development in this pathway.展开更多
Lihong Liu et al.1 from Columbia University recently reported in Nature the isolation of a collection of 19 SARS-CoV-2-neutralizing monoclonal antibodies(mAbs)from five infected patients with high plasma virus-neutral...Lihong Liu et al.1 from Columbia University recently reported in Nature the isolation of a collection of 19 SARS-CoV-2-neutralizing monoclonal antibodies(mAbs)from five infected patients with high plasma virus-neutralizing titers.These antibodies can neutralize SARS-CoV-2 in vitro,and nine of them exhibited exquisite potency,with 50%virus-inhibitory concentrations of 9 ng/mL or less.The strategy for isolation of these antibodies included sorting SARS-CoV-2 spike protein(S)-specific memory B cells by flow cytometry and single-cell sequencing.展开更多
基金funded by the XUST seeding grant and a national talent program grant(Grant numbers:2050122039 and 6119924022)funded by the National Health and Medical Research Council(Investigator 2025931)Australian Research Council(Laureate Fellowship FL180100109).
文摘The Janus kinase-signal transducer and activator of transcription(JAK-STAT)pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus.It plays a pivotal role in physiological functions,such as hematopoiesis,immune balance,tissue homeostasis,and surveillance against tumors.Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies,autoimmune diseases,hematologic disorders,and cancer.Due to its critical role in maintaining human health and involvement in disease,extensive studies have been conducted on this pathway,ranging from basic research to medical applications.Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level,laying the groundwork for therapeutic development targeting this pathway.Various strategies have been developed to restore its normal function,with promising therapeutic potential.Enhanced comprehension of these molecular mechanisms,combined with advances in protein engineering methodologies,has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications,thereby enhancing their efficiency and safety.In this review,we outline the structural basis that governs key nodes in this pathway,offering a comprehensive overview of the signal transduction process.Furthermore,we explore recent advances in cytokine engineering for therapeutic development in this pathway.
基金supported by the Strategic Priority Research Program of CAS(XDB37030204)the National Key Research and Development Program of China(2016YFD0500305)the Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control(2020XGZX031).
文摘Lihong Liu et al.1 from Columbia University recently reported in Nature the isolation of a collection of 19 SARS-CoV-2-neutralizing monoclonal antibodies(mAbs)from five infected patients with high plasma virus-neutralizing titers.These antibodies can neutralize SARS-CoV-2 in vitro,and nine of them exhibited exquisite potency,with 50%virus-inhibitory concentrations of 9 ng/mL or less.The strategy for isolation of these antibodies included sorting SARS-CoV-2 spike protein(S)-specific memory B cells by flow cytometry and single-cell sequencing.
