Bio-Me’s Post

Our preprint is now a peer review paper! How do cells survive glucose starvation? We care about this question because often when we measure how much glucose there is in tumors vs. normal tissue, we find less glucose in the tumor. We argue that the mechanism utilized by tumor cells to survive this stress are interesting drug targets because the tumor is glucose-starved and is, therefore, more dependent upon these mechanisms compared to normal, un-starved tissue. We know that when we have a lot of energy in our body (from food), we make fat, and when we have less energy, we burn fat. What is interesting is that if cells keep making fat while glucose-starved, they burn themselves out because making fat consumes antioxidants at a high rate. What we found is the mechanism by which cells reduce fatty acid synthesis (fat generation) and promote fatty acid oxidation (fat burn) to survive during glucose starvation. And that this mechanism is found in humans, mice, and yeast cells, so it's evolutionarily conserved. We also found that this metabolic switch is critical for tumor cells to generate tumors and for the aggressiveness of brain tumors in particular because there is low glucose in the brain. This work is in full collaboration with my dear friend and amazing scientist, Gabriel Leprivier, and his students Laura and Kai. In my group, Tal Levy, Khawla Alasad, and Ran Marciano led the project. We have fantastic scientists collaborating with us on this project: Gruenewald Thomas, Sarah-Maria Fendt , Almut Schulze, and Moshe Elkabets. This project was funded by: The Israel Academy of Sciences and Humanities cancer.org.il NIBN | The National Institute for Biotechnology in the Negev https://lnkd.in/dWe5QGMB

🎉 Exciting News! 🎉 I’m happy to share that our review paper, titled “LOXL2 in Non-Alcoholic Steatohepatitis (NASH): Insights into Fibrosis Pathogenesis and Therapeutic Potential,” has been published in Liver International Communications! In this review, we explore the role of Lysyl oxidase-like 2 (LOXL2) in liver fibrosis, particularly in the context of NASH. We delve into the mechanisms of LOXL2 in ECM remodeling, hepatic stellate cell activation, oxidative stress, and inflammation. Our findings highlight the therapeutic potential of LOXL2 inhibitors in reducing fibrosis and improving liver function. Key points include: • LOXL2’s Role in Fibrosis: Upregulation in fibrotic tissues and contribution to ECM remodeling in NASH. • Therapeutic Potential: Promise of LOXL2 inhibitors in preclinical studies. • Mechanisms in NASH: Activation of hepatic stellate cells, ECM protein cross-linking, and impacts on oxidative stress and lipid metabolism. • Development Challenges: Addressing species differences and tissue-specific effects. • Imaging Techniques: Potential of LOXL2-targeted imaging for non-invasive monitoring. A big thank you to my co-authors I. Joys Rachel, Rajnish Kumar , and Shailendra Asthana for their invaluable contributions. You can read the full paper here: https://lnkd.in/ggqtqYiu #LiverResearch #NASH #Fibrosis #LOXL2 #Research #OpenAccess #DBT #THSTI TRANSLATIONAL HEALTH SCIENCE AND TECHNOLOGY INSTITUTE

Exciting news! Our review, “Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches” has been published in EMBO molecular medicine. This review explores the profound metabolic changes in sepsis, with a focus on pyruvate metabolism. Pyruvate serves as a key metabolic link between glycolysis and mitochondrial oxidative phosphorylation. In sepsis, the activities of enzymes involved in pyruvate metabolism are significantly altered, contributing to hallmark features such as elevated lactate levels. We discuss how these enzyme activities are disrupted in sepsis and explore potential therapeutic strategies targeting these pyruvate-related enzymes to improve survival. You can find the full article here: https://lnkd.in/eNRVAEZs A big thank you to Jolien Vandewalle and Claude Libert for their contributions!

#Nanomaterials represent a promising frontier in treating hepatobiliary diseases, offering targeted drug delivery, improved bioavailability, and reduced systemic toxicity, making them an exciting area of research for hepatobiliary disease treatment. As a result, I am incredibly proud to announce that together with my friends Elchin Huseynov, and Rovshan Khalilov, have published our work titled 'Novel Nanomaterials for Hepatobiliary Diseases Treatment and Future Perspectives.' This collaboration has been a remarkable journey, and I'm grateful to have worked alongside such brilliant minds in advancing this important field of research. #Nanomaterials #Drugdelivery #Hepatobiliary Diseases #Future Perspectives

The 6th DECISION-Project General Assembly highlighted the development of novel treatments and prognostic tools for #chronicliverdisease, with a focus on multi-omics data integration, relevant preclinical models, and the design of a clinical trial to test a new combinatorial therapy in patients with acutely decompensated cirrhosis. Under the coordination of Pierre-Emmanuel Rautou, the project is making steady progress towards its goals. Read more: https://lnkd.in/dRpF6rX7 Huge thanks to all partners in the Consortium for your continued dedication! Fundació Clínic per a la Recerca Biomèdica - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Uniklinik RWTH Aachen Navarrabiomed, biomedical research centre YouHealth AB University of Bologna (Alma Mater Studiorum – Università di Bologna) UCL Università degli Studi di Padova (UNIPD) / University of Padua Università degli Studi di Torino Universitat de Barcelona EASL | The Home of Hepatology European Liver Patients' Association - ELPA concentris research management GmbH #Horizon2020

Exciting alert! 📚 A recent paper on Proteomic signatures has revolutionized risk prediction for common and rare diseases by combining high throughput proteomics with longitudinal cohort samples from the UK Biobank Pharma Proteomics Project. The study involved 41,931 individuals and measured ~3,000 plasma proteins using innovative PEA technology from Olink. This approach and clinical information led to the development of sparse prediction models for the 10-year incidence of 218 common and rare diseases, ranging from 81 to 6,038 cases. 🧪 Check out the full paper to delve into the fascinating findings: https://lnkd.in/gB_meXAY #Research #Proteomics #Healthcare #UKBiobank #Olink #NaturePortfolio #Arcadia Life Sciences

Our new article in the Cell Press journal Trends in Biochemical Sciences on "Protein lipoylation: mitochondria, cuproptosis, and beyond". Thanks to my talented students, my collaborators, and the TIBS editor Ms. Culbertson! #mitochondria #CellDeath #metabolism #cuproptosis #lipoylation Cheng-Han Lin Robert W. Sobol Jr. Sannie J. Culbertson https://lnkd.in/eAi4-nXC We discussed the recent discovery of cuproptosis, a novel form of cell death driven by copper binding to lipoylated proteins within mitochondria, showcasing a promising potential avenue for targeted cancer therapies. 1. Essential Role of Protein Lipoylation in Metabolism: Protein lipoylation is pivotal for the functionality of mitochondrial enzymes that drive the tricarboxylic acid (TCA) cycle, essential for efficient cellular energy metabolism. 2. Cuproptosis: A New Cell Death Pathway: The article highlights cuproptosis, a novel cell death pathway triggered by the binding of copper to lipoylated proteins, which disrupts mitochondrial function and leads to cell death. 3. Implications for Disease: Abnormal lipoylation levels are linked to significant health issues, including metabolic disorders and cancer, highlighting its critical role in maintaining metabolic health. 4. Therapeutic Opportunities: By targeting lipoylation and cuproptosis, new therapeutic strategies can be developed, particularly for treating cancers that exhibit metabolic vulnerabilities. 5. Call for Targeted Research: There is a pressing need for further research into the mechanisms regulating lipoylation and the development of pharmacological agents that can modulate this process, opening up potential new treatments for metabolic and proliferative diseases. https://lnkd.in/eAi4-nXC

Excited to share "Opportunities for Therapeutic Modulation of O-GlcNAc" ACS Publications Chemical Reviews with Alison Mody & Christina Woo, our contribution to an upcoming special issue "Drugging the Undruggable". Discovered 4 decades ago, O-GlcNAc 🟦 is a post-translational modification that plays roles in nearly every major cellular process. Notably, O-GlcNAc is found on many canonically undruggable proteins such as tau, α-synuclein, and transcription factors. Dysregulation of O-GlcNAc has been linked to numerous diseases including neurodegeneration, X-linked intellectual disability, cancer, diabetes, and immunological disorders, among others. Here we comprehensively review the biochemistry of O-GlcNAc, development of inhibitors targeting the O-GlcNAc cycling enzymes, research linking specific O-GlcNAc sites to disease, and clinical progress on targeting O-GlcNAc. We close discussing next-generation tools that leverage induced proximity to modulate O-GlcNAc on specific proteins, which will allow for detailed mechanistic probing of O-GlcNAc in biology. We hope this serves as a valuable resource both for O-GlcNAc researchers and for translational researchers more broadly thinking about post-translational modifications and their therapeutic relevance. https://lnkd.in/gksDP5F4 #glycotime

Excited to share my 18th publication and 2nd from my postdoc work at George Mason University..this time with Jorge Fernandez Davila Jeffrey L. Moran Luis Rodriguez Geraldine Grant [ Journal: Molecular Biology of the Cell -Impact Factor: 3.1] 𝐄𝐱𝐩𝐥𝐨𝐫𝐢𝐧𝐠 𝐍𝐨𝐯𝐞𝐥 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜 𝐀𝐯𝐞𝐧𝐮𝐞𝐬 𝐢𝐧 𝐈𝐝𝐢𝐨𝐩𝐚𝐭𝐡𝐢𝐜 𝐏𝐮𝐥𝐦𝐨𝐧𝐚𝐫𝐲 𝐅𝐢𝐛𝐫𝐨𝐬𝐢𝐬 𝐓𝐡𝐫𝐨𝐮𝐠𝐡 𝐀𝐝𝐯𝐚𝐧𝐜𝐞𝐝 𝟑𝐃 𝐂𝐞𝐥𝐥 𝐂𝐮𝐥𝐭𝐮𝐫𝐞 𝐌𝐨𝐝𝐞𝐥𝐬 We are excited to share groundbreaking findings from our recent study on idiopathic pulmonary fibrosis (IPF), a challenging and often fatal lung condition. By utilizing a state-of-the-art 3D hydrogel system derived from decellularized lung matrices of IPF patients, our research provides a deeper understanding of fibroblast behaviour in a more physiologically IPF environment. Key insights from our study indicate significant differences in the phenotype of IPF fibroblasts when cultured in 3D hydrogels compared to traditional 2D cultures. These fibroblasts not only show altered contractility but also lose the typical marker of α-smooth muscle actin, indicating a shift in their functional state. More importantly, they exhibit an increased expression of proinflammatory cytokines, underscoring a potential role in modulating immune responses within the lung. This research paves the way for new therapeutic strategies, particularly in targeting fibroblast-immune cell interactions, offering hope for more effective treatments for IPF patients. We believe that such advanced models not only enhance our understanding of IPF pathophysiology but also serve as crucial platforms for the development and testing of novel therapeutics. Let's continue to push the boundaries of science to find better solutions for IPF and similar conditions.  #IPF #LungDisease #BiomedicalResearch #3DCellCulture #InnovativeTherapies Link:

The first preprint in a series from the RESOLUTE consortium is out! This study dives into the systematic interrogation of solute carrier transporters (SLCs) and their relationships with cellular metabolism, using metabolomics and transcriptomics. #RESOLUTE #SLC #Metabolism https://lnkd.in/dgEA4yyU