Peter Bou Dib, PhD’s Post

High throughput organellar electrophysiology of TMEM175 and TPC2 from freshly isolated lysosomes recorded on the SyncroPatch 384. 🔎What are TMEM175 and TPCS? Proton leak channel transmembrane protein 175 (TMEM175) and the lysosomal two-pore channel (TPC) are intracellular ion channels, whose consideration has significantly increased as potential therapeutic targets highlighting the necessity for high-throughput electrophysiology techniques, including patch clamp. ❓Why are they considered potential therapeutic targets? Intracellular ion channels play a potential role connecting lysosomal homeostasis with pathophysiological conditions such as Parkinson’s disease and cancer. 💡What Axxam achieved. Together with Nanion Technologies we have created assays for exploring the functionality and pharmacology of lysosomal channels in their native state, offering innovative tools for the drug discovery sector.   Find out more by reading the application note: https://lnkd.in/dsnMPMJm #drugdiscovery #patchclamp #electrophysiology #ionchannels #intracellularchannels

#IHC #antibody #FGFR2b   FGFR2b Recombinant Rabbit mAb (SDT-423-18) Catalog Number: S0B2231 Location: Cell membrane, Secreted Application: IHC-P, WB, FC(Extra)   FGFR2b is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. FGFR2b has important roles in embryonic development and tissue repair, especially bone and blood vessels. Recent studies have found that about 30% of patients overexpress FGFR2b protein, which may be used as a new biomarker and research target for gastric cancer.   Welcome to request samples: info@starter-bio.com Find more: https://lnkd.in/gepkpCNu   #biotech #lifescience #recombinant #CDx #IVD #cancer #pathology #Immunohistochemistry

In a recent study, researchers found that the human #tumor suppressor PDCD4 plays a critical role in inhibiting translation initiation by interacting directly with ribosomes. This discovery sheds light on the #molecular mechanisms of translation regulation and provides valuable insights into the link between #tumorigenesis and translation inhibition. The findings, obtained through cryo-EM analysis, highlight the potential of PDCD4 as a target for therapeutic interventions in #cancer. To learn more about this groundbreaking research, click the link to access the full article: https://lnkd.in/gPG4_3S8 #CancerResearch #TranslationRegulation #RibosomeInteractions #PDCD4 #cells #cellresearch

"Supramolecular artificial Nano-AUTACs enable tumor-specific metabolism protein degradation for synergistic immunotherapy" by Jun Cao, Nicholas Peppas and their groups in #Science #Advances. https://lnkd.in/gMrbh5JG #Autophagy-targeting chimera (AUTAC) has emerged as a powerful modality that can selectively degrade tumor-related pathogenic proteins, but its low bioavailability and nonspecific distribution significantly restrict their therapeutic efficacy. Inspired by the #guanine structure of AUTAC molecules, we here report supramolecular artificial Nano-AUTACs (GM NPs) engineered by AUTAC molecule GN [an indoleamine 2,3-dioxygenase (IDO) degrader] and nucleoside analog methotrexate (MTX) through supramolecular interactions for tumor-specific protein degradation. Their #nanostructures allow for precise localization and delivery into cancer cells, where the intracellular acidic environment can disrupt the supramolecular interactions to release MTX for eradicating tumor cells, modulating tumor-associated macrophages, activating dendritic cells, and inducing autophagy. Specifically, the #induced #autophagy facilitates the released GN for degrading immunosuppressive IDO to further enhance effector T cell activity and inhibit tumor growth and metastasis. This study offers a unique strategy for building a nanoplatform to advance the field of AUTAC in tumor immunotherapy.

High throughput organellar electrophysiology of TMEM175 and TPC2 from freshly isolated lysosomes recorded on the SyncroPatch 384. 🔎What are TMEM175 and TPCS? Proton leak channel transmembrane protein 175 (TMEM175) and the lysosomal two-pore channel (TPC) are intracellular ion channels, whose consideration has significantly increased as potential therapeutic targets highlighting the necessity for high-throughput electrophysiology techniques, including patch clamp. ❓Why are they considered potential therapeutic targets? Intracellular ion channels play a potential role connecting lysosomal homeostasis with pathophysiological conditions such as Parkinson’s disease and cancer. 💡What Axxam achieved. Together with Nanion Technologies we have created assays for exploring the functionality and pharmacology of lysosomal channels in their native state, offering innovative tools for the drug discovery sector.   Find out more by reading the application note: https://lnkd.in/dsnMPMJm #drugdiscovery #patchclamp #electrophysiology #ionchannels #intracellularchannels

Metabolic flux technology with the #Seahorse bioanalyzer has emerged as a standard technique in #cellular metabolism studies, allowing for simultaneous kinetic measurements of respiration and glycolysis. Methods to extend the utility and versatility of the metabolic flux assay would undoubtedly have immediate and wide-reaching impacts. A platform that couples the metabolic flux assay with high-content fluorescence imaging to simultaneously provide means for normalization of respiration data with cell number; analyse cell cycle distribution; and quantify mitochondrial content, fragmentation state, membrane potential, and mitochondrial reactive oxygen #species. Integration of fluorescent dyes directly into the metabolic flux assay generates a more complete data set of mitochondrial features in a single assay. Moreover, application of this integrated strategy revealed insights into mitochondrial function following PGC1a and PRC1 inhibition in pancreatic cancer and demonstrated how the Rho-GTPases impact mitochondrial dynamics in #breastcancer. Read More: https://lnkd.in/gSekt8cd

🔬 Excited to share some insights from my research on M0 macrophage staining to evaluate lipid order/disorder distribution using the microenvironmental fluorescent dye, Di-4-ANEPPDHQ. 📸 This professional image, captured by confocal microscope, reveals the intricate lipid organization within immature M0 macrophages. Analyzing the lipid distribution, we can gain a deeper understanding of membrane dynamics and cellular functions. lipid order helps elucidate membrane fluidity and its role in cell signaling, providing insights into how lipid domains contribute to various physiological processes. This knowledge enhances our understanding of immune cell function and has significant implications for therapy, drug delivery systems, and cancer treatment. Stay tuned for more updates on this exciting project! 🔬🧪💡 #Research #Macrophage #ConfocalMicroscopy #LipidOrder #CellBiology #FluorescentDye #Therapy #DrugDelivery #CancerTreatment

🎉 Excited to Share My Latest Research Publication! 📚✨ I'm thrilled to announce the publication of my latest research paper on Cyclin-dependent kinase 2 (CDK2) and its inhibition using spirooxindoles. CDK2 is a critical regulator of cell cycle checkpoints and plays a pivotal role in cancer cell proliferation. Targeting CDK2 has significant potential for cancer treatment, making it a highly druggable hotspot. In our study, we investigated three spirooxindoles (SOI1, SOI2, and SOI3) to understand their inhibitory mechanisms against CDK2. Through a combination of molecular docking and molecular dynamics (MD) simulations, we explored their interactions at the molecular level. The binding free energies we calculated aligned well with experimental results, validating our computational approach. Key findings include: 🔬 Identification of crucial binding residues in the CDK2 active site and T-loop phosphorylation. 💡 Energy decomposition analysis revealing molecular mechanics (MM) energy as the primary contributor to stabilizing inhibitor binding. 🏆 SOI1 demonstrated the strongest binding affinity, particularly interacting robustly with the crucial residue T160, essential for kinase activation. These insights provide a solid foundation for developing potent CDK2 inhibitors using the spirooxindole scaffold, potentially advancing cancer treatment strategies. Check out the full paper to dive deeper into our findings! #Research #CancerResearch #CDK2 #Spirooxindoles #MolecularDynamics #DrugDiscovery #Science #Innovation https://lnkd.in/gEGt6gbY

#Immunotherapy | A #CAR Body Shop 🤔 | Generation of #CARTcells in vivo using #Lentiviral #Vectors displaying a Multi-Domain Fusion Ligand 👍 | Major Advance from Byoung Ryu & Co. at #BLOOD Online Now 👏 | #cancer | Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high cost and manufacturing complexities hinder their widespread use. T Here* to overcome these hurdles, Umoja Biopharma researchers have developed the VivoVecTM platform, a lentiviral vector capable of generating CAR T-cells in vivo. They describe the incorporation of T cell activation and costimulatory signals onto the surface of VivoVecTM particles (VVPs) in the form of a multi-domain fusion protein and show enhanced in vivo transduction and improved CAR-T cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into non-human primates resulted in the robust generation of anti-CD20 CAR T-cells and the complete depletion of B cells for more than 10 weeks. These data validate the VivoVecTM platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies. *https://lnkd.in/eNjvUPdX Celentyx Ltd Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady GRAPHICAL ABSTRACT