XORTX Therapeutics Inc.’s Post

Dr. Matam Vijay-Kumar, professor in the Department of Physiology and Pharmacology, recently detailed the case of a patient who developed metastatic colon cancer after prolonged daily consumption of inulin. "All of our lab studies have shown the same thing — that diets rich in highly refined, fermentable fiber like inulin may increase the risk of gastrointestinal cancer," he told UToledo News. "While not a smoking gun, this patient's story is compelling evidence that matches what we and others have seen in the lab." The case report was published in the journal Gastro Hep Advances. Read more in UToledo News: https://buff.ly/3UReC7N #UToledoMed #research

Endo-lysosomes express several functionally diverse ion channels, crucial for regulating organelle trafficking and intracellular signalling as well as maintaining the acidic luminal pH for optimal enzymatic activity. Dysfunctions within the endo-lysosomal system are associated with multiple disorders including lysosomal storage disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Lysosomal ion channels have, therefore, gained significant attention as potential targets for novel therapeutics.   Due to their localisation to small intracellular compartments, endo-lysosomal ion-channels have been historically challenging to study using conventional patch-clamp techniques. However, recent advances in lysosomal biology make it possible to enlarge and extract endo-lysosomes for subsequent recording using manual patch-clamp electrophysiology. This approach allows for the characterisation of channel function within the native environment, facilitating better physiological understanding.   In this video we demonstrate our endo-lysosomal extraction technique to enable the study of ion channels found on the lysosomal membrane. Find out more at: https://lnkd.in/ejXtUHJG #ionchannels #drugdiscovery #cro #patchclamp #lifesciences #alzheimersdisease #parkinsonsdisease

🔬Citation Break!📖 This citation studies the effects of various molecules on alpha-synuclein aggregation and neurodegeneration. rPeptide's Alpha-Synuclein (cat# S-1001) was used by the authors to investigate the impact of those molecules while comparing results to in vivo experiments. Paper: https://rb.gy/nqltoj  Alpha-Synuclein: https://rb.gy/38rtqk #Reasearch #Development #rPeptide #AlphaSynuclein #Citations 

Analysing MSC-extracellular vesicle angiogenic and immunomodulatory properties: Christina Holmes at Florida State University and collaborators aimed to compare the angiogenic and immunomodulatory potentials, as well as the protein and miRNA cargo compositions, of EVs derived from the two most common clinical sources of adult mesenchymal stromal/stem cells (MSC), bone marrow and adipose tissue, across various passage numbers to identify the optimal MSC source for clinically translatable EV-based therapies https://lnkd.in/eUETMypw In vitro tube formation assays using human umbilical vein endothelial cells revealed that the tissue source and passage number significantly influence the angiogenic capacity of EVs. An article co-authored by Yuan Liu, li sun and Yan Li #extracellularvesicles #exosomes #angiogenesis #multiomics #MSCs #Vesiculab

New research details the generation of human bone marrow-like #Organoids from human induced pluripotent #StemCells #iPSC. These bone marrow organoids recapitulate many characteristics of hematopoietic microenvironment and could prove to be a physiologically relevant in vitro model for studying bone marrow diseases and hematopoietic development. Organoid structure was evaluated using both #Confocal and #Multiphoton #Microscopy. Click to view the article: https://lnkd.in/ekwYujJp

I am very pleased to share that my first publication, ‘Investigating G-protein coupled receptor signalling with light-emitting biosensors,’ has been published this month in Frontiers in Physiology. In this review, we present some of the fluorescent and bioluminescent biosensors available to interrogate GPCR signalling, illustrate some of the key findings which have been made possible by these tools, and discuss their limitations and possible future developments. The review can found here: https://lnkd.in/dy3yf2ve

𝗔𝗱𝘃𝗮𝗻𝗰𝗶𝗻𝗴 𝗱𝗿𝘂𝗴 𝗱𝗶𝘀𝗰𝗼𝘃𝗲𝗿𝘆 𝘁𝗵𝗿𝗼𝘂𝗴𝗵 𝗵𝗶𝗴𝗵-𝘁𝗵𝗿𝗼𝘂𝗴𝗵𝗽𝘂𝘁 𝗼𝗿𝗴𝗮𝗻𝗲𝗹𝗹𝗲 𝘀𝘁𝘂𝗱𝗶𝗲𝘀 Intracellular ion channels like TMEM175 and TPC2 play key roles in cellular physiology, with their dysfunction linked to conditions like Parkinson’s and cancer. Understanding their function is essential for developing new therapies. In collaboration with Axxam we’ve developed advanced assays to study lysosomal channels in their native environment, marking a breakthrough for the drug discovery industry. Here are our key insights: ✅ First-ever recordings from isolated lysosomes using the SyncroPatch 384, addressing the challenge of studying lysosomal channels directly in native conditions. ✅ Successful recordings of TPC2 and TMEM175 channels, validated through specific pharmacology, opening new paths for lysosomal pharmacology research. ✅ Our Organellar Chips and ultra-low cell density method provide robust access to electrophysiology across multiple organelles, offering a cost-effective and scalable approach. Curious to learn more? Discover more in the application note: https://ow.ly/qXVN50Tw7nK #Electrophysiology #IonChannels #DrugDiscovery #TMEM175 #OrganellarChannels #SyncroPatch384

Check out this excellent multidisciplinary work, just published in Angewandte Chemie, about the discovery of a new class of small-molecule inhibitors as a promising therapeutic approach in #fibroplast-related diseases, by George KOLLIAS and Alexis Matralis, BSRC Alexander Fleming. Special and huge congrats to Vasiliki Mavrikaki, a talented PhD student from the Laboratory of Organic Chemistry of National and Kapodistrian University of Athens contributing with her synthetic skills to this outstanding achievement!! #inhibitors #medicinalchemistry #fibrosis

CryoEM structures of two isoforms of the full length insulin receptor bound to Insulin-like Growth Factor 2 (IGF2), showing multiple conformations even at full saturation. The insulin receptor (the isoforms IR-A or IR-B in this study) are transmembrane tyrosine kinases that form dimers and bind to 4 molecules of insulin, IGF1, or IGF2 per dimer at two sites per monomer. 3D classification of the cryoEM data resulted in particles with distinct conformations. The two most populated groups showed either a symmetrical T-shaped structure with two IGF2 molecules bound on each side (similar to the insulin-bound structure) or an symmetrical T-shape with two IGF2 molecules on one side, and only one on the other. A third class was observed at a lower resolution that may only have two IGF2 molecules bound. The authors surprisingly note that the asymmetric T-shape is the most common state in the dataset, even though IGF2 was at saturating levels. Insulin and IGF2 bind the same two sites, but with different detailed molecular interactions. The authors also solve the apo-state of IR-B, comparing it to the previously published apo IR-A structure, which both show a different conformation to the bound forms, with hugely separated membrane spanning regions. This is a great example of the power of cryoEM for structurally characterising flexible (the transmembrane and kinase domains were not resolved) and/or conformationally heterogeneous samples, as from a single sample (at least) two structures were solved. Furthermore, it was even possible to quantify the relative abundance of each conformation in a given sample. Nature Portfolio, University of Texas Southwestern Medical Center, Columbia University #insulin #receptor #metabolism #cryoEM #structuralbiology #signalling #membraneprotein #kinase

I am very happy to share our paper published in Cardiovascular Research. In this paper, we identify the role of KDM5 family of histone demethylases in the maturation of cardiomyocytes (CMs). We find that expression of KDM5 progressively declines with age in murine CMs. Inhibiting KDM5 improves the maturation of iPSC-derived CMs by increasing the expression of genes involved in fatty acid oxidation, oxidative phosphorylation, and sarcomere formation, resulting in improved mitochondrial function and myofibril organization.