Article
Biochemistry & Molecular Biology
Marcela Montilla, Isabel Atienza-Navarro, Francisco Jose Garcia-Cozar, Carmen Castro, Francisco Javier Rodriguez-Martorell, Felix A. Ruiz
Summary: Polyphosphate (polyP) plays an important modulatory role in the binding of von Willebrand factor (VWF) and Factor VIII (FVIII) in blood coagulation, and may be used in developing new therapies to activate VWF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Jerry Ware
Summary: The utility of mouse models in dissecting the molecular basis of hemostasis and thrombosis is well recognized, with recent advancements including the humanization of key receptor-ligand axes. Despite their power, limitations exist in applying findings to human primary hemostasis and thrombosis mechanisms.
Article
Hematology
Andrew Yee, Manhong Dai, Stacy E. Croteau, Jordan A. Shavit, Steven W. Pipe, David Siemieniak, Fan Meng, David Ginsburg
Summary: The study demonstrated the utility of phage display and NGS in characterizing diverse anti-VWF antibody reactivities, which allowed for the identification of immunoreactive regions within VWF. This approach revealed distinct patterns of immunoreactivity between different patients with VWD and highlighted the importance of complete removal of the VWF propeptide in replacement products.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Cell Biology
Yaping Zhang, Samuel M. Ehrlich, Cheng Zhu, Xiaoping Du
Summary: The GPIb-IX complex plays a crucial role in mediating initial platelet adhesion and converting mechanical force into intracellular signals. Thrombin binding to GPIb-IX cooperatively stimulates platelet response. GPIb-IX signaling involves multiple pathways and molecular interactions, leading to calcium mobilization, integrin activation, and granule secretion.
Article
Biochemical Research Methods
Wen-Ching Lin, Hao-Cheng Tang, Han Ying Wang, Chia-Yi Kao, You-Chiun Chang, Athena Hsu Li, Shi-Bing Yang, Kurt Yun Mou
Summary: This study introduces a unique mutagenesis method called the reverse Kunkel method, which combines the advantages of user-defined mutagenesis and random mutagenesis. By coupling with phage display and yeast display selections, the method successfully generates improved antibodies with enhanced affinity and immunostaining performance.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Klaus Bonazza, Roxana E. Iacob, Nathan E. Hudson, Jing Li, Chafen Lu, John R. Engen, Timothy A. Springer
Summary: This study investigates the regulatory role of N-linker and C-linker in the binding of A1 to GPIb alpha. The results show that the N-linker decreases the affinity of A1 for GPIb alpha, with a stronger contribution from its O-glycan moiety. Additionally, the N-linker regulates the hydrogen deuterium exchange, thermal stability, and urea-induced unfolding of A1. In contrast, the C-linker has no significant effect on the affinity of A1 for GPIb alpha.
Article
Biochemical Research Methods
Andrew P. Cazier, Olivia M. Irvin, Lizmarie S. Chavez, Saachi Dalvi, Hannah Abraham, Nevinka Wickramanayake, Sreenivas Yellayi, John Blazeck
Summary: This article introduces a yeast diversifying base editor, yDBE, which functions in vivo and utilizes a CRISPR-dCas9-directed cytidine deaminase base editor to diversify DNA in a targeted, rapid, and high-breadth manner. By enhancing the mutation rate and employing scaffolded guide constructs, the yDBE platform is able to improve the affinity of proteins and generate diversified libraries efficiently.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pete Heinzelman, Philip A. A. Romero
Summary: ACE2 variants with improved specificity towards Ang-II and wild-type or greater Ang-II hydrolytic activity were discovered using yeast display-based liquid chromatography screen and directed evolution, which have potential as therapeutic agents for multiple human diseases.
Review
Chemistry, Multidisciplinary
Yajie Wang, Pu Xue, Mingfeng Cao, Tianhao Yu, Stephan T. Lane, Huimin Zhao
Summary: Directed evolution aims to accelerate the natural evolution process of biological molecules and systems through gene diversification and library screening, serving as a powerful tool for engineering improved functions in proteins, metabolic pathways, and whole genomes. Common strategies include gene diversification, screening/selection methods, and continuous evolution, with applications in nucleic acids, proteins, pathways, genetic circuits, viruses, and cells. Challenges and future perspectives in directed evolution are also discussed.
Article
Cardiac & Cardiovascular Systems
Monica Bray, Melda A. Guzel, Fong Lam, Andrew Yee, Miguel A. Cruz, Rolando E. Rumbaut
Summary: COVID-19 is associated with changes in the activity and quality of VWF, but these changes are not specific to COVID-19. Similar changes in VWF activity and quality are observed in hospitalized patients with or without COVID-19. Further research is needed to understand the mechanisms responsible for qualitative changes in VWF in COVID-19 and other critical illnesses.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2022)
Article
Hematology
Paola Colpani, Luciano Baronciani, Francesca Stufano, Giovanna Cozzi, Marco Boscarino, Maria Teresa Pagliari, Eugenia Biguzzi, Flora Peyvandi
Summary: This study evaluated four different assays to diagnose and detect various von Willebrand disease (VWD) variants. The VWF:GPIbM-automated assay was the most effective in diagnosing type 2B, while the VWF:RCo assays were the most effective in detecting type 2M and 2M/2A variants. The VWF:GPIbM ELISA overestimated the activity of type 2B patients lacking high-molecular-weight multimers (HMWM). Using a VWF activity/VWF:antigen ratio cut-off of 0.70 reduced the number of misdiagnosed patients by half.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemical Research Methods
Elisabeth Laurent, Anna Sieber, Benjamin Salzer, Anna Wachernig, Jacqueline Seigner, Manfred Lehner, Rene Geyeregger, Bernhard Kratzer, Ulrich Jager, Renate Kunert, Winfried F. Pickl, Michael W. Traxlmayr
Summary: Engineered stable CD19-ECD variants (SuperFolder) have been developed, with improved expression rates and efficient purification in monomeric forms, overcoming obstacles in the development and analysis of CD19-targeted therapeutics. These mutants preserve the wild type sequence (>98.8%) and hold promise for a range of applications in basic immunology and CD19-targeted cancer immunotherapy.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Medical Laboratory Technology
Neil S. Harris, J. Peter Pelletier, Maximo J. Marin, William E. Winter
Summary: This article briefly introduces the importance of von Willebrand disease and the challenges faced by clinical laboratories, provides a detailed explanation of VWF biosynthesis and structure, and then discusses the distinguishing characteristics of different types of VWD and the clinical laboratory tests available for diagnosis.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Renan Eugenio Araujo Piraine, Vitoria Sequeira Goncalves, Alceu Goncalves dos Santos Junior, Rodrigo Casquero Cunha, Pedro Machado Medeiros de Albuquerque, Neida Lucia Conrad, Fabio Pereira Leivas Leite
Summary: A Cell Surface Display system was successfully developed in Saccharomyces cerevisiae to express BoHV-5 glycoprotein D; recombinant protein expression was confirmed through experiments; the approach and plasmid used not only allow effective immobilization of proteins on yeast cell surface, but also serve as a platform for the development of immunobiologicals.
BIOTECHNOLOGY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Bo Zhao, Shutong Xu, Xianchi Dong, Chafen Lu, Timothy A. Springer
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Xianchi Dong, Bo Zhao, Roxana E. Iacob, Jianghai Zhu, Adem C. Koksal, Chafen Lu, John R. Engen, Timothy A. Springer
Article
Multidisciplinary Sciences
Jianchuan Wang, Xianchi Dong, Bo Zhao, Jing Li, Chafen Lu, Timothy A. Springer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Multidisciplinary Sciences
Abhay Kotecha, Quan Wang, Xianchi Dong, Serban L. Ilca, Marina Ondiviela, Rao Zihe, Julian Seago, Bryan Charleston, Elizabeth E. Fry, Nicola G. A. Abrescia, Timothy A. Springer, Juha T. Huiskonen, David I. Stuart
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Xianchi Dong, Bo Zhao, Fu-Yang Lin, Chafen Lu, Bruce N. Rogers, Timothy A. Springer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Hematology
Xianchi Dong, Nina C. Leksa, Ekta Seth Chhabra, Joseph W. Arndt, Qi Lu, Kevin E. Knockenhauer, Robert T. Peters, Timothy A. Springer
Article
Biology
Juan Feng, Xianchi Dong, Jennifer Pinello, Jun Zhang, Chafen Lu, Roxana E. Iacob, John R. Engen, William J. Snell, Timothy A. Springer
Article
Biochemistry & Molecular Biology
Maren Buss, Nicole Tegtmeyer, Jennifer Schnieder, Xianchi Dong, Jing Li, Timothy A. Springer, Steffen Backert, Hartmut H. Niemann
Article
Hematology
Xianchi Dong, Timothy A. Springer
Article
Biology
Fang Tian, Bei Tong, Liang Sun, Shengchao Shi, Bin Zheng, Zibin Wang, Xianchi Dong, Peng Zheng
Summary: Research indicates that the N501Y mutation in SARS-CoV-2 variants strengthens its interaction with ACE2, leading to an increased transmission rate, highlighting the need for close monitoring of future mutations in the virus' RBD.
Article
Biology
Juan Feng, Xianchi Dong, Adam DeCosta, Yang Su, Fiona Angrisano, Katarzyna A. Sala, Andrew M. Blagborough, Chafen Lu, Timothy A. Springer
Summary: The study identifies antibodies against Plasmodium berghei HAP2 that block the transmission of malaria by inhibiting fertilization. These antibodies cross-react with HAP2 in multiple plasmodial species, providing insights for the development of a vaccine to block malaria transmission. Additionally, the crystal structures of HAP2 ectodomain and the mechanism of inhibition are characterized in this research.
Article
Immunology
Yuxin Chen, Lin Chen, Shengxia Yin, Yue Tao, Liguo Zhu, Xin Tong, Minxin Mao, Ming Li, Yawen Wan, Jun Ni, Xiaoyun Ji, Xianchi Dong, Jie Li, Rui Huang, Ya Shen, Han Shen, Changjun Bao, Chao Wu
Summary: This study found that the CoronaVac booster induces broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Multidisciplinary Sciences
Juan Feng, Xianchi Dong, Yang Su, Chafen Lu, Timothy A. Springer
Summary: This study investigates the fusion structure and intermediate states of the HAP2 protein from red algae. The postfusion structure of HAP2 is trimeric, but the prefusion structure has been difficult to determine. The study reveals the importance of three fusion loops in D2 for the formation of the postfusion state.
NATURE COMMUNICATIONS
(2022)
Letter
Biochemistry & Molecular Biology
Mengwen Huang, Xingchao Pan, Xinling Wang, Qingfei Ren, Bei Tong, Xianchi Dong, Gaoxiang Ge, Lu Lu, Shibo Jiang, Jianfeng Chen
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Immunology
Wen Liu, Yi Zou, Kaiming Li, Haiqing Zhong, Longbo Yu, Shushan Ge, Yisheng Lai, Xianchi Dong, Qiang Xu, Wenjie Guo
Summary: Pharmacological inhibition of IDO1 has shown to be an effective approach for cancer treatment. However, existing inhibitors have limited response and unclear biomarkers in clinical practice. This study identified a potent inhibitor, B37, which targets apo-IDO1 and has strong antitumor efficacy by activating the host immune system.
JOURNAL OF IMMUNOLOGY
(2022)