ArticleNature communications2023
Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
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35 citing papers in PubMed, 40 citations in OpenAlex.
- Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comprehensive metabolomic profiling of Egyptian Salvia species reveals promising leads for chemopreventive and anti-inflammatory drug development: In vitro and In silico study.Scientific reports · 2026Article
- Ligand-driven modulation of chaperone-cochaperone networks shapes proteostasis outcomes.Protein science : a publication of the Protein Society · 2026Article
- Targeting protein protein interactions and their modulators to enable new therapeutic strategies for human diseases.NPJ systems biology and applications · 2026Review
- Label-Free Target Discovery Strategy for Natural Active Products.Biomolecules · 2026Review
- Embracing diversity: Post-translational modifications, the chaperone code, and the emergence of new chaperone entities.Cell stress & chaperones · 2026Review
- BDDN: bayesian dynamic differential network analysis in cancer proteomics.BMC bioinformatics · 2026Article
- HSP70 governs permeability and mechanotransduction in primary human endothelial cells.FEBS open bio · 2026Article
- Discovery of the MELK-Nucleostemin Axis in Glioblastoma: Implications for p53 Regulation and Tumor Progression.Journal of microbiology and biotechnology · 2026Article
- MED-PPIS: Multi-order Moments External Graph Attention Network with Dual-Axis Attention for Protein-Protein Interaction Site Prediction.Interdisciplinary sciences, computational life sciences · 2025Article
- Mapping Dysfunctional Protein-Protein Interactions in Disease.Journal of visualized experiments : JoVE · 2025Article
- PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease.Trends in biochemical sciences · 2025Review
- In vivo imaging of heat shock protein 90: Diagnostic tool and support for Hsp90-targeted therapy.Cell stress & chaperones · 2025Review
- Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease.Cells · 2025Review
- Systems-Level Interactome Mapping Reveals Actionable Protein Network Dysregulation Across the Alzheimer's Disease Spectrum.Research square · 2025Article
- Review
- A systems biology approach to unveil shared therapeutic targets and pathological pathways across major human cancers.Computational and structural biotechnology journal · 2025Article
- Characterizing protein-protein interactions with thermal proteome profiling.Current opinion in structural biology · 2024Review
- Introducing dysfunctional Protein-Protein Interactome (dfPPI) - A platform for systems-level protein-protein interaction (PPI) dysfunction investigation in disease.Current opinion in structural biology · 2024Review
Corrections and comments
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Authors and funding
31 authors at 6 institutions in 3 countries.
Anna Rodina *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-3894-6438
Chao Xu *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Chander S Digwal *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-8784-1096
Suhasini Joshi *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Yogita Patel *Department of Biochemistry, Groupe de Recherche Axé sur la Structure des Protéines, McGill University, Montreal, QC, H3G 0B1, Canada.
Anand R SanthaseelaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-3513-9224
Sadik BayChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Swathi MeruguChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Aftab AlamChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Pengrong YanChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Chenghua YangChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Tanaya RoychowdhuryChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Palak PanchalChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Liza ShresthaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Yanlong KangChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Sahil SharmaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7281-9224
Justina AlmodovarChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Adriana CorbenDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Mary L AlpaughChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-0008-2718
Shanu ModiDepartment of Medicine, Division of Solid Tumors, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Monica L GuzmanDepartment of Medicine, Division of Hematology Oncology, Weill Cornell Medicine, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-9262-8246
Teng FeiDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7888-1715
Tony TaldoneChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Stephen D GinsbergDepartments of Psychiatry, Neuroscience & Physiology & the NYU Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Hediye Erdjument-BromageDepartment of Neuroscience and Physiology and Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Thomas A NeubertDepartment of Neuroscience and Physiology and Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Katia Manova-TodorovaCell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Meng-Fu Bryan TsouCell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Jason C YoungDepartment of Biochemistry, Groupe de Recherche Axé sur la Structure des Protéines, McGill University, Montreal, QC, H3G 0B1, Canada.ORCID http://orcid.org/0000-0002-9158-3090
Tai WangChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. wangtaifr@gmail.com.ORCID http://orcid.org/0000-0001-9984-9634
Gabriela ChiosisChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chiosisg@mskcc.org.ORCID http://orcid.org/0000-0003-0486-6920
Memorial Sloan Kettering Cancer Center · USMcGill University · CANeurosciences Institute · USCornell University · USMaimonides Medical Center · USNathan Kline Institute for Psychiatric Research · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MProject 3: Structural Basis for grp94 Drug Development and Chaperone FunctionP01CA186866 · NCI · OHIO STATE UNIVERSITY · PI LI, ZIHAI · 2015 to 2019
$6.7MImpact of sex differences on the trajectory of interactome dysfunctions across the AD spectrumR01AG074004 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2025
$6.0MChaperome networks in Alzheimer's diseaseR01AG067598 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI ARANCIO, OTTAVIO, CHIOSIS, GABRIELA · 2021 to 2025
$5.9MSelective interactome vulnerability across the Alzheimer’s disease spectrumR01AG072599 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI GABRIELA CHIOSIS, STEPHEN D GINSBERG · 2023 to 2026
$5.4M[18F]-PU-AD epichaperome PET imaging probeRF1AG071805 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, DUNPHY, MARK P. · 2022 to 2025
$4.8MNeuropathology and inflammation in a nonhuman primate model of insulin resistance/metabolic syndromeR01AG085572 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STEPHEN D GINSBERG, PETER J HAVEL · 2024 to 2026
$3.8MSmall molecule Hsp90 inhibitors in AD treatmentU01AG032969 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA · 2010 to 2014
$3.5MBiomarkers for predicting response to Hsp90 therapyR01CA172546 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, DUNPHY, MARK P. · 2013 to 2017
$2.9MA chemical chaperomics platform for ADR56AG061869 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA · 2018 to 2019
$1.8MSelective interactome vulnerability across the Alzheimer’s disease spectrumR56AG072599 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2021
$1.2MNCI NIH HHS P01 CA186866NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA172546NIA NIH HHS R01 AG067598NIA NIH HHS R01 AG072599NIA NIH HHS R01 AG074004NIA NIH HHS R01 AG085572NIA NIH HHS R56 AG061869NIA NIH HHS R56 AG072599NIA NIH HHS RF1 AG071805NIA NIH HHS U01 AG032969
Abstract
Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.
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NeoplasmsProtein Interaction MapsAcclimatizationHumansProtein Interaction MappingProteomeProteome
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