Project description:The proteome of human plaque, fibrous cap, core, and media was unveiled using fully automated sample preparation platform AccelerOme and cutting-edge DIA mass spectrometry.
Project description:Cell polarity is used to guide asymmetric divisions and create morphologically diverse cells. We find that two oppositely oriented cortical polarity domains present during the asymmetric divisions in the Arabidopsis stomatal lineage are reconfigured into polar domains marking ventral (pore-forming) and outward facing domains of maturing stomatal guard cells. Proteins that define these opposing polarity domains were used as baits in miniTurboID-based proximity labeling. Among differentially enriched proteins we find SOSEKIs and their effector ANGUSTIFOLIA, protein kinase CKII and LC8-type DYNEIN LIGHT CHAIN1 as polar scaffolds. Using AI-facilitated protein structure prediction models, we identify their potential interaction interfaces. Functional and localization analysis of polarity protein OPL2 and its newly discovered partners suggest a positive interaction with mitotic microtubules and a potential role in cytokinesis. This combination of cutting-edge proteomics and structural modeling with live cell imaging provides insights into how polarity is rewired in different cell types and cell cycle stages.
Project description:In this study, a series of cutting-edge technologies such as protein extraction, enzyme digestion, liquid chromatography-mass spectrometry tandem analysis and bioinformation analysis were organically combined to study the quantitative proteome of samples.
Project description:NCOMMS-24-54326: Despite the STING-type-I interferon pathway playing a key role in effective anti-tumor immunity, the therapeutic benefit of direct STING agonists appears limited. In this study, we used several artificial intelligence techniques and patient-based multi-omic data to show that Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1), which hydrolyzes STING-activating cyclic GMP-AMP (cGAMP), is a safer and more effective STING-modulating target than direct STING agonism in multiple solid tumors. We then leveraged our generative chemistry artificial intelligence-based drug design platform to facilitate the design of ISM5939, an orally bioavailable ENPP1-selective inhibitor capable of stabilizing extracellular cGAMP and activating bystander antigen-presenting cells without inducing either toxic inflammatory cytokine release or tumor-infiltrating T-cell death. In murine syngeneic models across cancer types, ISM5939 synergizes with targeting the PD-1/PD-L1 axis and genotoxic chemotherapy in suppressing tumor growth with good tolerance. Our findings provide new evidence supporting ENPP1 as a novel innate immune checkpoint across solid tumors and reports the first AI design-aided ENPP1 inhibitor, ISM5939, as a cutting-edge STING modulator for cancer therapy, paving a new path for immunotherapy advancements.
Project description:ALFAOMEGA-RETRÒ will be exploited to retrospectively collect clinical and imaging data and archival samples to be used for validation and correlative studies on markers discovered by cutting-edge translational projects within the AIRC5x1000 program "Insights into the evolving heterogeneity of colorectal cancer (CRC): from mechanism to therapies" (an ongoing multi-institutional research program).
