Citrin Foundation’s Post

We are thrilled to share that our latest research has been published in the journal Thrombosis Research: "Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting". Full paper here: https://lnkd.in/dBYs_8nA This study, which falls under my #PhD, aimed to identify novel genetic variants associated with the endpoint of major adverse cardiovascular events (MACEs) 12 months after percutaneous coronary intervention (PCI) by designing and analyzing a customized targeted gene panel. In an exploratory analysis, new genetic determinants involved in altered lipid metabolism were identified, suggesting a more relevant role of this process in the occurrence of MACEs in patients with acute coronary syndrome undergoing PCI. Nevertheless, further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process. #cardiovascular #pharmacogenetics #personalizedmedicine

📢 After approval of funding within Horizon Europe, the European Rare Diseases Research Alliance (ERDERA) has been launched today.  Through the collaborative work of 178 organizations joining forces to support and develop robust patient need-led research, ERDERA aims at making Europe a world leader in rare disease research and innovation.   🔬 The ultimate goal is to improve the health and well being of 30 million people living with a rare disease in Europe building on the groundwork set up by the European Joint Programme on Rare Diseases.   🔬 Fondazione Telethon is engaged in ERDERA both as a funding organization of the joint transnational calls for research to be launched yearly and also through Tigem and San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) for the development of advanced therapies for Rare Diseases.

New research from Yale School of Medicine has discovered that the gene "Glis2" is a component of PKD signalling and may also be a new target for the treatment of the disease. Until now, the Glis2 gene was not included in any of the known pathways that have been investigated for PKD One of the research scientists, Xin Tian MD states, "When I found that the disease progression was significantly prevented in in vivo studies, I was very excited and realised that the Glis2 can play a crucial role in further dissecting PKD signaling and enriching our understanding of mechanisms of the human ADPKD, and also could lead to developing treatments of the disease." You can read more about the study here: https://lnkd.in/g_3_zZUb

🔬 A research team led by CeMM Adjunct PI Thomas Reiberger (Medizinische Universität Wien) gained new insights that could improve treatment of liver fibrosis. Repeated or chronic liver injury, for example by viral hepatitis or alcohol consumption, triggers the complicated molecular process of scaring underlying this disease. The study, first authored by Oleksandr Petrenko, examines gene activities at various stages of liver fibrosis and could contribute to a first-time therapy. The results were published in the journal iScience (https://bit.ly/3PncqS3) ➡️ read more: bit.ly/48LqUlC

🌟 Excited to share a major scientific advancement from our team at NMC Royal Khalifa City, now validated by the Karolinska Institutet! Struck et al. (2024) confirmed the phased TNF-mediated endothelial response in acute sepsis, a finding we predicted in our temporal transcriptomic analyses. Our research identified distinct stages of gene expression during sepsis, providing new insights into the progression of this critical condition. The Karolinska team’s validation underscores the importance of TNF-endothelial response in sepsis and highlights the potential for targeted therapies focused on endothelial dysfunction. A proud milestone for NMC Healthcare and a step forward in sepsis management! 🚀 #SepsisResearch NMC Healthcare Karolinska Institutet #EndothelialResponse #TNF #HealthcareInnovation #Genomics #MachineLearning https://lnkd.in/d3RkkbQp https://lnkd.in/djjKXKJQ

Why mention Göttingen Minipigs on #WorldAlzDay? To enable the development of new treatment paradigms and modalities that improve the lives of patients diagnosed with Alzheimer´s Disease (AD), a model in Göttingen Minipigs has been developed to study the impact of early intervention targeting the amyloid-β and tau levels in the cerebrospinal fluid (CSF), as increased levels of amyloid-β and tau levels in the CSF are speculated to correlate with the risk of developing AD. Read the 2024 paper, "Mice and minipigs with compromised expression of the Alzheimer’s disease gene SORL1 show cerebral metabolic disturbances on hyperpolarized [1-13C]pyruvate and sodium MRI" https://lnkd.in/dfZs2rh6 [Open access] If you are interested in or have questions concerning this genetically altered Göttingen Minipigs model, please contact CSO Lars Siim Madsen. #EllegaardGöttingenMinipigs #GöttingenMinipigs

My postdoctoral work is now online in Nature Communications. With this work, we discovered and annotated a new miRNA gene (miR-6236) previously unreported in human genome. MiR-6236 is highly expressed in myeloid cells of adipose tissue, especially during obesity. By creating global and myeloid specific loss-of-function mice strains, we show that myeloid cell derived miR-6236 potentiates insulin signaling in adipocytes during obesity progression to protect from obesity-associated metabolic dysfunctions. https://lnkd.in/gjShREPb

Don’t stop at BRAF V600E.. When DNA sequencing for BRAF/MAP2K1/KRAS/NRAS mutations is negative in the workup of #histiocytoses.. start thinking about gene fusions (actually preferable to start thinking about fusions from the start!)... Below is a KIF5B::ALK fusion from targeted RNA-sequencing making a diagnosis of this entity - https://lnkd.in/g6sKjqEP Clinicopathological features of this rare disease (ALK-positive histiocytosis) -         Presentation any time from infant to adult -         Can be single system (most often CNS) or multisystem involvement (CNS, bone, lungs..) -         Bone lesions can look like Erdheim-Chester disease -         Beware – ALK IHC may show dot-like positivity that may be interpreted as negative.. - Almost always ALKex20 fused to KIF5Bex24 MOST IMPORTANTLY..  like almost all histiocytoses… targeted inhibition of molecular driver is remarkably effective and the therapy of choice. Multiple ALK inhibitors have been used in this entity (#crizotinib, #alectinib, #lorlatinib, #brigatinib, #ceritinib..) - 100% response rate (!) in the above linked work. #WilsonCentreforBloodCancerGenomics #PrecisionDiagnostics #AllHaemRNA #FusionPanels #hemepath #NGS 

🔎 New insights into Adenosine Deaminase 2 deficiency (DADA2) pathogenesis uncover potential new treatment strategies  DADA2 is a complex genetic disorder affecting blood vessels, the immune and hematopoietic system, often leading to bone marrow failure. Due to the absence of an ADA2 gene equivalent in rodent models, our understanding of this condition has been limited so far.  🔬 In their latest publication in #CommunicationBiology, Alessandra Mortellaro, Anna Pistocchi and their respective teams addressed this gap by developing a new zebrafish model lacking the ADA2-like gene cecr1b, and reported:  ✔️ replication of the symptoms seen in humans with DADA2, including inflammation, vascular, and hematopoietic dysfunctions;  ✔️ correction of stem cells defects by blocking inflammation or by using treatments that target the ADA2 receptor pathway;  ✔️restoration of normal neutrophil production with human ADA2 supplementation. 📖 For all the details, read the full paper👉https://lnkd.in/dFsYHnq3  #RareDiseases #DiseaseModelling #GeneTherapy #CellTherapy 

GNAO1 encephalopathies are a rare disease leading to epilepsy, severe motor dysfunctions, and intellectual disability 🧠 from birth. These conditions are caused by mutations in the GNAO1 gene 🧬 and present a major challenge for treatment due to the large number of mutations involved, making it difficult to develop universal therapeutic strategies.   After years of research, Vladimir Katanaev's team, Professor at the Faculté de médecine - UNIGE, has made a major discovery regarding the protein encoded by the GNAO1 gene, Gαo 🧬. Contrary to expectations, most mutations do not cancel or accelerate the function of this protein, but give it a whole new one.   More info here 👉 https://lnkd.in/e-BMYE9e   This discovery, recently published in the Journal of Clinical Investigation, opens up new avenues in therapeutic research for these rare diseases.   #GNAO1 #research #rarediseases #medicine #UNIGE