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CHIOSIS LAB MSKCC 

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A unique chemical biology approach to understand, diagnose, and treat cellular processes associated with chronic molecular stress, with the ultimate goal of developing novel therapeutic options for use in the clinic.
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Introducing dysfunctional Protein-Protein Interactome (dfPPI) - A Platform for systems-level protein-protein interaction (PPI) dysfunction investigation in disease

Click the image to read a special issue of Current Opinions in Structural Biology Biophysical Methods (2024): Protein Networks in Health and Disease featuring an article by Chiosis Lab MSKCC and collaborators. 

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N-Glycans' Effect on Pathologic Protein Conformations in Disease

Click the image to read an adaptation from recently published paper "N-Glycosylation as a Modular of Protein Conformation and Assembly in Disease" by Chiosis Lab MSKCC and collaborators in Biomolecules MDPI.

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Synthesis & Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders

Click the image to read the latest work by Chiosis Lab MSKCC and collaborators in Biomedicines MDPI Special Issue Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases. 

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Click the image to read "Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation."

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Epichaperome-targeted Myocardial Imaging by      I-PU-H71 PET
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Check out this preprint via Research Square.

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Stress biology: Complexity and multfariousness in health and disease

Click here to read an overview of the captivating 12th International Symposium on Heat Chock Proteins in Biology, Medicine and the Environment highlighting recent progress in understanding stress responses and molecular chaperones.

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N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease

Take a look at this recent publication in Biomolecules MDPI. 

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Experimental traumatic brain injury increases epichaperome formation

Read our latest publication in Neurobiology of Disease on epichaperome formation in response to cellular stress.

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Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action

Check out our recent publication in Biomedicines MDPI and discover the secret behind prolonged drug action and therapeutic efficacy of epichaperome agents Zelavespib and Icapamespib.

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Unraveling the Complex Web of Protein Interactions in Diseases

Check out this article that Dr. Chiosis wrote in partnership with Scientific American Custom Media.

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Epichaperomics can identify disease-related changes in protein-protein interaction networks

Check out this VideoByte produced by Research Square on the latest Nature Communications paper.

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Unveiling the Intricate Dance of HSP90: A Master Conductor of Cellular Responses in Health and Disease

Check out this blog that Dr. Chiosis wrote on Nature Reviews Molecular Cell Biology paper. 

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Structural and functional complexity of HSP90 in cellular homeostasis and disease

Make sure to check out this paper on the different compositions of HSP90-co-chaperone complexes in health and disease. 

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MSK Research Highlights, June 29, 2023

Check out our feature in MSK Research Highlights for June 2023 mentioning how we developed a systems-level platform called epichaperomics, to map changes in interactors among thousands of proteins involved in cancer-related processes. 

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Epichaperomics: Illuminating the Secrets of Protein Interactions in Disease Research

Check out this blog that Dr. Chiosis wrote on this paper. 

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Unveiling the Role of Protein Glycosylation: Insights into Conformational Dynamics and Disease Mechanisms

Check out this blog that Dr. Chiosis wrote on this paper. 

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How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view

Check out this Structure article on how too much sugar can lead to cancer! 

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Nature Communications Editors' Highlight on Cancer Research

Check out our feature in the Nature Communications Editors' Highlights page as one of the top 50 papers published in cancer research. 

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Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation

Read about how an unbiased 'Epichaperomics' platform helped us to identify context-dependent mechanisms by which cancer cells enhance the fitness of mitotic protein networks.  

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Targeting stressor-induced dysfunctions in protein–protein interaction networks via epichaperomes

Read about our opinion on targeting dysfunctions in protein-protein interactions via epichaperomes and implications of epichaperome therapy via a precision medicine approach. 

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Synthesis of 124I-labeled epichaperome probes and assessment in visualizing pathologic protein-protein interaction networks in tumor bearing mice

Check out our detailed protocol on the synthesis of epichaperome targeting clinical agents, [124I]-PU-H71 and [124I]-PU-AD and specific steps in the use of these reagents to visualize pathologic PPI networks. 

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Epichaperomes as a Gateway to Understanding, Diagnosing, and Treating Disease Through Rebalancing Protein–Protein Interaction Networks

This book chapter highlights several chemical probes, from epichaperome disrupters to epichaperome affinity-purification tools and epichaperome detection and quantitation probes, and the use of these probes as therapeutic strategies aimed at normalizing PPI networks, especially in cancer and neurodegenerative diseases. 

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How Aberrant N-Glycosylation Can Alter Protein Functionality and Ligand Binding: an Atomistic View

Our collaborator, the colombo team, integrated computational and experimental tools to unveil the role of N-glycosylation of specific residues in glucose-regulated protein 94 (GRP94) to modulates its internal dynamics and shed light on the determinants of GRP94 response to ligands. 

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Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

We used an innovative and unbiased epichaperomic platform to show how epichaperome targeting probes makes the cancer cells maxed-out their capacity to remodel PPI networks and how the cells respond in the presence of additional therapeutic stress at this state. Check out our feature on EinPressWire: https://www.einpresswire.com/article/557136874/a-cellular-traffic-jam-for-precision-medicine-in-cancer

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Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia
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Disease-specific interactome alterations via epichaperomics: the case for Alzheimer’s disease
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The penalty of stress - Epichaperomes negatively reshaping the brain in neurodegenerative disorders
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News: Study Reveals a New Way That Stress and Aging Lead to Alzheimer’s

Researchers find that a targeted approach being developed to treat certain cancers also appears to help rewire brain circuitry in Alzheimer’s disease.

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News: Bull’s-Eye: Imaging Technology Could Confirm When a Drug Is Going to the Right Place

By combining an imaging agent with a targeted therapy, MSK researchers can determine which tumors are likely to respond to the drug and then confirm that the drug is reaching the tumor.

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Our latest article was featured on the cover of the journal of Cancer Cell

Pillarsetty N, Jhaveri K, Taldone T, et al. Paradigms for Precision Medicine in Epichaperome Cancer Therapy. Cancer Cell. 2019;36(5):559–573.e7. doi:10.1016/j.ccell.2019.09.007

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