Chuchu Wang
Stanford University
H-index: 12
North America-United States
About Chuchu Wang
Chuchu Wang, With an exceptional h-index of 12 and a recent h-index of 12 (since 2020), a distinguished researcher at Stanford University, specializes in the field of Neurodegenerative disease.
His recent articles reflect a diverse array of research interests and contributions to the field:
Multi-omics microsampling for the profiling of lifestyle-associated changes in health
Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor
Deep learning-based pseudo-mass spectrometry imaging analysis for precision medicine
TidyMass an object-oriented reproducible analysis framework for LC–MS data
Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein
massDatabase: utilities for the operation of the public compound and pathway database
Chuchu Wang Information
University | Stanford University |
---|---|
Position | ___ |
Citations(all) | 567 |
Citations(since 2020) | 538 |
Cited By | 156 |
hIndex(all) | 12 |
hIndex(since 2020) | 12 |
i10Index(all) | 12 |
i10Index(since 2020) | 12 |
University Profile Page | Stanford University |
Chuchu Wang Skills & Research Interests
Neurodegenerative disease
Top articles of Chuchu Wang
Multi-omics microsampling for the profiling of lifestyle-associated changes in health
Authors
Xiaotao Shen,Ryan Kellogg,Daniel J Panyard,Nasim Bararpour,Kevin Erazo Castillo,Brittany Lee-McMullen,Alireza Delfarah,Jessalyn Ubellacker,Sara Ahadi,Yael Rosenberg-Hasson,Ariel Ganz,Kevin Contrepois,Basil Michael,Ian Simms,Chuchu Wang,Daniel Hornburg,Michael P Snyder
Journal
Nature Biomedical Engineering
Published Date
2024/1
Current healthcare practices are reactive and use limited physiological and clinical information, often collected months or years apart. Moreover, the discovery and profiling of blood biomarkers in clinical and research settings are constrained by geographical barriers, the cost and inconvenience of in-clinic venepuncture, low sampling frequency and the low depth of molecular measurements. Here we describe a strategy for the frequent capture and analysis of thousands of metabolites, lipids, cytokines and proteins in 10 μl of blood alongside physiological information from wearable sensors. We show the advantages of such frequent and dense multi-omics microsampling in two applications: the assessment of the reactions to a complex mixture of dietary interventions, to discover individualized inflammatory and metabolic responses; and deep individualized profiling, to reveal large-scale molecular fluctuations as …
Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering
Authors
Ying Lai,Chunyu Zhao,Zhiqi Tian,Chuchu Wang,Jiaqi Fan,Xiao Hu,Jia Tu,Tihui Li,Jeremy Leitz,Richard A Pfuetzner,Zhengtao Liu,Shengnan Zhang,Zhaoming Su,Jacqueline Burré,Dan Li,Thomas C Südhof,Zheng-Jiang Zhu,Cong Liu,Axel T Brunger,Jiajie Diao
Journal
Proceedings of the National Academy of Sciences
Published Date
2023/10/31
α-synuclein (α-Syn) is a presynaptic protein that is involved in Parkinson’s and other neurodegenerative diseases and binds to negatively charged phospholipids. Previously, we reported that α-Syn clusters synthetic proteoliposomes that mimic synaptic vesicles. This vesicle-clustering activity depends on a specific interaction of α-Syn with anionic phospholipids. Here, we report that α-Syn surprisingly also interacts with the neutral phospholipid lysophosphatidylcholine (lysoPC). Even in the absence of anionic lipids, lysoPC facilitates α-Syn-induced vesicle clustering but has no effect on Ca2+-triggered fusion in a single vesicle–vesicle fusion assay. The A30P mutant of α-Syn that causes familial Parkinson disease has a reduced affinity to lysoPC and does not induce vesicle clustering. Taken together, the α-Syn–lysoPC interaction may play a role in α-Syn function.
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor
Authors
Kailu Yang,Chuchu Wang,Alex JB Kreutzberger,K Ian White,Richard A Pfuetzner,Luis Esquivies,Tomas Kirchhausen,Axel T Brunger
Journal
Proceedings of the National Academy of Sciences
Published Date
2023/3/28
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide inhibitors based on the Wuhan strain sequence are less efficacious. Here, we report an Omicron-specific peptide inhibitor designed based on the structure of the Omicron HR1HR2 postfusion bundle. Specifically, we inserted an additional residue in HR2 near the Omicron HR1 K969 residue to better accommodate the N969K mutation and relieve the distortion in the structure of the HR1HR2 postfusion bundle it introduced …
Deep learning-based pseudo-mass spectrometry imaging analysis for precision medicine
Authors
Xiaotao Shen,Wei Shao,Chuchu Wang,Liang Liang,Songjie Chen,Sai Zhang,Mirabela Rusu,Michael P Snyder
Journal
Briefings in Bioinformatics
Published Date
2022/9
Liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics provides systematic profiling of metabolic. Yet, its applications in precision medicine (disease diagnosis) have been limited by several challenges, including metabolite identification, information loss and low reproducibility. Here, we present the deep-learning-based Pseudo-Mass Spectrometry Imaging (deepPseudoMSI) project (https://www.deeppseudomsi.org/), which converts LC–MS raw data to pseudo-MS images and then processes them by deep learning for precision medicine, such as disease diagnosis. Extensive tests based on real data demonstrated the superiority of deepPseudoMSI over traditional approaches and the capacity of our method to achieve an accurate individualized diagnosis. Our framework lays the foundation for future metabolic-based precision medicine.
TidyMass an object-oriented reproducible analysis framework for LC–MS data
Authors
Xiaotao Shen,Hong Yan,Chuchu Wang,Peng Gao,Caroline H Johnson,Michael P Snyder
Journal
Nature Communications
Published Date
2022/7/28
Reproducibility, traceability, and transparency have been long-standing issues for metabolomics data analysis. Multiple tools have been developed, but limitations still exist. Here, we present the tidyMass project (https://www.tidymass.org/), a comprehensive R-based computational framework that can achieve the traceable, shareable, and reproducible workflow needs of data processing and analysis for LC-MS-based untargeted metabolomics. TidyMass is an ecosystem of R packages that share an underlying design philosophy, grammar, and data structure, which provides a comprehensive, reproducible, and object-oriented computational framework. The modular architecture makes tidyMass a highly flexible and extensible tool, which other users can improve and integrate with other tools to customize their own pipeline.
Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Authors
Kailu Yang,Chuchu Wang,K Ian White,Richard A Pfuetzner,Luis Esquivies,Axel T Brunger
Journal
Proceedings of the National Academy of Sciences
Published Date
2022/4/19
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus–host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2–3.8 Å resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme …
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein
Authors
Kailu Yang,Chuchu Wang,Alex JB Kreutzberger,Ravi Ojha,Suvi Kuivanen,Sergio Couoh-Cardel,Serena Muratcioglu,Timothy J Eisen,K Ian White,Richard G Held,Subu Subramanian,Kendra Marcus,Richard A Pfuetzner,Luis Esquivies,Catherine A Doyle,John Kuriyan,Olli Vapalahti,Giuseppe Balistreri,Tom Kirchhausen,Axel T Brunger
Journal
Proceedings of the National Academy of Sciences
Published Date
2022/10/4
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors, which block formation of the so-called heptad repeat 1 and 2 (HR1HR2) six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. We performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit …
massDatabase: utilities for the operation of the public compound and pathway database
Authors
Xiaotao Shen,Chuchu Wang,Michael P Snyder
Journal
Bioinformatics
Published Date
2022/10/1
Summary One of the major challenges in liquid chromatography coupled to mass spectrometry data is converting many metabolic feature entries to biological function information, such as metabolite annotation and pathway enrichment, which are based on the compound and pathway databases. Multiple online databases have been developed. However, no tool has been developed for operating all these databases for biological analysis. Therefore, we developed massDatabase, an R package that operates the online public databases and combines with other tools for streamlined compound annotation and pathway enrichment. massDatabase is a flexible, simple and powerful tool that can be installed on all platforms, allowing the users to leverage all the online public databases for biological function mining. A detailed tutorial and a case study are provided in the Supplementary Material …
Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson's disease
Authors
Shengnan Zhang,Yu-Qing Liu,Chunyu Jia,Yeh-Jun Lim,Guoqin Feng,Enquan Xu,Houfang Long,Yasuyoshi Kimura,Youqi Tao,Chunyu Zhao,Chuchu Wang,Zhenying Liu,Jin-Jian Hu,Meng-Rong Ma,Zhijun Liu,Lin Jiang,Dan Li,Renxiao Wang,Valina L Dawson,Ted M Dawson,Yan-Mei Li,Xiaobo Mao,Cong Liu
Journal
Proceedings of the National Academy of Sciences
Published Date
2021/6/29
The spread of pathological α-synuclein (α-syn) is a crucial event in the progression of Parkinson’s disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn in the amyloid over monomeric state to initiate cell-to-cell transmission. However, the molecular mechanism underlying this selective binding is unknown. Here, we perform an array of biophysical experiments and reveal that LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus, especially residues 118 to 140, of α-syn. The formation of amyloid fibrils not only can disrupt the intramolecular interactions between the C terminus and the amyloid-forming core of α-syn but can also condense the C terminus on fibril surface, which remarkably increase the binding affinity of α-syn to the receptors. Based on this mechanism, we …
Hsp27 chaperones FUS phase separation under the modulation of stress-induced phosphorylation
Authors
Zhenying Liu,Shengnan Zhang,Jinge Gu,Yilun Tong,Yichen Li,Xinrui Gui,Houfang Long,Chuchu Wang,Chunyu Zhao,Jinxia Lu,Lin He,Ying Li,Zhijun Liu,Dan Li,Cong Liu
Journal
Nature structural & molecular biology
Published Date
2020/4
Protein phase separation drives the assembly of membraneless organelles, but little is known about how these membraneless organelles are maintained in a metastable liquid- or gel-like phase rather than proceeding to solid aggregation. Here, we find that human small heat-shock protein 27 (Hsp27), a canonical chaperone that localizes to stress granules (SGs), prevents FUS from undergoing liquid−liquid phase separation (LLPS) via weak interactions with the FUS low complexity (LC) domain. Remarkably, stress-induced phosphorylation of Hsp27 alters its activity, leading Hsp27 to partition with FUS LC to preserve the liquid phase against amyloid fibril formation. NMR spectroscopy demonstrates that Hsp27 uses distinct structural mechanisms for both functions. Our work reveals a fine-tuned regulation of Hsp27 for chaperoning FUS into either a polydispersed state or a LLPS state and suggests an essential role …
Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly
Authors
Chuchu Wang,Jia Tu,Shengnan Zhang,Bin Cai,Zhenying Liu,Shouqiao Hou,Qinglu Zhong,Xiao Hu,Wenbin Liu,Guohui Li,Zhijun Liu,Lin He,Jiajie Diao,Zheng-Jiang Zhu,Dan Li,Cong Liu
Journal
Nature Communications
Published Date
2020/3/24
Vesicle associated membrane protein 2 (VAMP2/synaptobrevin2), a core SNARE protein residing on synaptic vesicles (SVs), forms helix bundles with syntaxin-1 and SNAP25 for the SNARE assembly. Prior to the SNARE assembly, the structure of VAMP2 is unclear. Here, by using in-cell NMR spectroscopy, we describe the dynamic membrane association of VAMP2 SNARE motif in mammalian cells, and the structural change of VAMP2 upon the change of intracellular lipid environment. We analyze the lipid compositions of the SV membrane by mass-spectrometry-based lipidomic profiling, and further reveal that VAMP2 forms distinctive conformations in different membrane regions. In contrast to the non-raft region, the membrane region of cholesterol-rich lipid raft markedly weakens the membrane association of VAMP2 SNARE motif, which releases the SNARE motif and facilitates the SNARE assembly. Our work …
Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau
Authors
Xiaojuan Ma,Yi Zhu,Jinxia Lu,Jingfei Xie,Chong Li,Woo Shik Shin,Jiali Qiang,Jiaqi Liu,Shuai Dou,Yi Xiao,Chuchu Wang,Chunyu Jia,Houfang Long,Juntao Yang,Yanshan Fang,Lin Jiang,Yaoyang Zhang,Shengnan Zhang,Rong Grace Zhai,Cong Liu,Dan Li
Journal
elife
Published Date
2020/4/6
Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer’s disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration.
Chuchu Wang FAQs
What is Chuchu Wang's h-index at Stanford University?
The h-index of Chuchu Wang has been 12 since 2020 and 12 in total.
What are Chuchu Wang's top articles?
The articles with the titles of
Multi-omics microsampling for the profiling of lifestyle-associated changes in health
Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor
Deep learning-based pseudo-mass spectrometry imaging analysis for precision medicine
TidyMass an object-oriented reproducible analysis framework for LC–MS data
Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein
massDatabase: utilities for the operation of the public compound and pathway database
...
are the top articles of Chuchu Wang at Stanford University.
What are Chuchu Wang's research interests?
The research interests of Chuchu Wang are: Neurodegenerative disease
What is Chuchu Wang's total number of citations?
Chuchu Wang has 567 citations in total.
What are the co-authors of Chuchu Wang?
The co-authors of Chuchu Wang are David S. Eisenberg, Jiajie Diao, Lin Jiang, Ying Lai.