Ka Yang

Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells

Kevin Dong, Qing Yu, Ka Yang, Yue Hong et autres

Live-cell activity-based protein profiling (ABPP) with mass spectrometry enables the proteome-wide quantification of compound reactivity, yet resulting datasets often suffer from low data completeness for high-priority targets and do not give users the option to measure compound-induced protein changes within the same …

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PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors

Andrew D. Huber, Wenwei Lin, Kwan‐Young Jung, Shyaron Poudel et autres

Proteolysis-targeting chimeras (PROTACs) containing a target protein ligand linked to an E3 ubiquitin ligase ligand induce target protein degradation through E3 recruitment. Most PROTACs bind a surface cleft of the protein of interest rather than a buried pocket. Using the nuclear receptor …

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Characterization of a dual degrader of MDM2 and GSPT1

Ira Tandon, Paulina N. Esguerra, Chunrong Li, Huan Sun et autres

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Ex vivo recapitulation of intramuscular mRNA vaccination with naïve and recall antigens using a human Lymphoid Follicle Chip platform

Yunhao Zhai, Min‐Wen Ku, Ka Yang, Aditya Patil et autres

Summary Predicting the efficacy and toxicity of intramuscular mRNA vaccines remains challenging. Here, we describe an ex vivo human cell-based model that replicates immune responses to lipid nanoparticle (LNP)-based mRNA vaccines that require intramuscular injection. Vaccines are administered into a biomimetic muscle …

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TMT-Based Multiplexed (Chemo)Proteomics on the Orbitrap Astral Mass Spectrometer

Yuchen He, Ka Yang, S. Li, Martin Zeller et autres

Ongoing advancements in instrumentation has established mass spectrometry (MS) as an essential tool in proteomics research and drug discovery. The newly released Asymmetric Track Lossless (Astral) analyzer represents a major step forward in MS instrumentation. Here, we evaluate the Orbitrap Astral mass …

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Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions

Wenxue Li, Abhijit Dasgupta, Ka Yang, Shisheng Wang et autres

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Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis

Guimei He, Pingping Liu, Xiaoyan Xuan, Min Zhang et autres

Inflammatory bowel disease (IBD) is a chronic, relapsing, and remitting disease characterized by chronic inflammation in the gastrointestinal tract. The exact etiology and pathogenesis of IBD remain elusive. Although ELF-1 has been known to be highly expressed in epithelial cells for past …

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Potent and selective SETDB1 covalent negative allosteric modulator reduces methyltransferase activity in cells

Mélanie Uguen, Devan J. Shell, Madhushika Silva, Yu Deng et autres

A promising drug target, SETDB1, is a dual methyl-lysine (Kme) reader and methyltransferase implicated in cancer and neurodegenerative disease progression. To help understand the role of the triple Tudor domain (3TD) of SETDB1, its Kme reader, we first identify a low micromolar …

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Human and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome

Jay M. Yarbro, Xian Han, Abhijit Dasgupta, Ka Yang et autres

Murine models of Alzheimer’s disease (AD) are crucial for elucidating disease mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse models of amyloidosis. We identified shared pathways by …

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MassIVE MSV000100336 - Proteomic profiling of NSD2 degrader

Ka Yang

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Human-mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome

Junmin Peng, Jay M. Yarbro, Xian Han, Abhijit Dasgupta et autres

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Human-mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome

Jay M. Yarbro, Xian Han, Abhijit Dasgupta, Ka Yang et autres

Abstract Murine models of Alzheimer’s disease (AD) are crucial for elucidating disease mechanisms but have limitations in fully representing AD molecular complexities. We comprehensively profiled age-dependent brain proteome and phosphoproteome ( n > 10,000 for both) across multiple mouse models of amyloidosis. …

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