The purpose of this review is to provide an overview of redox mechanisms, sources and antioxidants that control signaling events in ECs. To pursue these molecular and pharmacological goals, researchers need to use animal models that facilitate the elucidation of tumor angiogenesis mechanisms and the testing of antiangiogenic therapies. Using transgenic lines marking developing vMCs in zebrafish embryos, we find that vMCs are recruited by arterial-fated vessels and that the process is flow dependent. The analysis and the interpretation of the data can be found in the associated article [1]. ROS HOMEOSTASIS AND METABOLISM: A DANGEROUS LIASON IN CANCER CELLS. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. Massimo Santoro ha illustrato come le scoperte della biologia e della genetica hanno aperto nuove strade per la cura del cancro, delineando il ruolo dei geni nell’insorgenza dei tumori e le nuove possibilità di individuare strategie terapeutiche. It is envisioned that this small vertebrate system will help in the understanding of pathogenesis for numerous metabolic-related disorders in humans and in the identification of their therapeutic treatments. In particular, we describe which molecules are involved in redox signaling and how they influence the relationship between ECs and other vascular component with regard to angiogenesis. Here we describe a protocol for fast and reliable (13)C-isotope-based in vivo metabolic profiling. The Alk5-dependent induction of zeb1a and foxo1a is required for this morphogenetic process: zeb1a is responsible for driving LPM migration around the gut, whereas foxo1a regulates LPM predisposition to iSMC differentiation. Santoro, M.M., Beltrame, M., Panáková, D., Siekmann, A.F., Tiso, N., Venero Galanternik, M., Jung, H.M., Weinstein, B.M. Massimo M. Santoro obtained is Master Diploma from University of Turin, Italy and his PhD in Molecular and Cellular Biology from the Open University, London, UK. ©2018 BY SANTORO LAB. Human UBIAD1 is a nonmitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Often, the same mechanisms are responsible for the insurgence of vascular-associated pathologies. SANTORO LAB Department of Biology, University of Padua, Italy Despite these crucial roles, the origin of iSMCs and the mechanisms responsible for their differentiation and function remain largely unknown in vertebrates. In this article we used transgenic zebrafish lines that express compartment-specific isoforms of the roGFP2-Orp1 and Grx1-roGFP2 biosensors, described in Panieri et al (2017) [1], to test the contribute of the pentose phosphate pathway and of the glutathione biosynthesis in the antioxidant capacity of myocardial and endothelial cells in vivo. By generating novel transgenic (Tg) zebrafish lines that express compartment-specific Rogfp2-Orp1 and Grx1-Rogfp2 sensors we analyzed cytosolic, mitochondrial, and the nuclear redox state of endothelial cells and cardiomyocytes of living zebrafish embryos. FASHIONING BLOOD VESSELS BY ROS SIGNALLING AND METABOLISM. Indeed, recent studies indicate that endothelial primary cilia within blood vessels function as blood flow mechanosensors.3 In ECs, cilia use flow information to regulate their presence with more and longer cilia present in vascular areas with low shear stress and at vascular branch points or areas of high curvature.4 Clinical research studies have shown an augmented risk of intracranial aneurysm, as well as an increased risk of hemorrhage in patients with cilia deficiency.5 In agreement, recent work on both mouse and zebrafish models suggest a specific role for cilia in intracranial aneurysm and cerebral-vascular integrity.6,7 Overall, several indications support a role for cilia in cranial vessel stability. Rogfp2-based transgenic zebrafish lines represent valuable tools to characterize the impact of redox changes in living tissues and offer new opportunities for studying metabolic driven antioxidant response in biomedical research. We identified a novel autosomal recessive congenital restrictive cardiomyopathy, caused by a near complete loss-of-function of KIF20A. This is a crucial biological event in all vertebrates. Genetically-encoded Rogfp2 fluorescent probes have become powerful tools for real-time detection of redox events. Grave lutto per Rita Dalla Chiesa dopo il dolore per Fabrizio Frizzi: qualche giorno fa, pare a causa di una In particolare, si occupa di una rara malattia oculare in cui questi processi … à morto lâ ex presidente delle Terme di Fiuggi, il professor Massimo Santoro. Intestinal smooth muscle cells (iSMCs) are a crucial component of the adult gastrointestinal tract and support intestinal differentiation, peristalsis and epithelial homeostasis during development. This procedure represents a valuable approach for researchers interested in studying the effect of gene manipulation on lipid metabolism in zebrafish and in understanding the genetic conditions that result in metabolism dysfunction. Tra questi anche suo genero, Massimo Santoro, scomparso a soli 52 anni stroncato da una grave malattia. Loss of UBIAD1 reduces the cytosolic pool of the antioxidant CoQ10 and leads to ROS-mediated lipid peroxidation in vascular cells. To identify the cause, we performed genetic, in vitro and in vivo studies. Combining pharmacological and genetic approaches, we show that TGFβ/Alk5 signaling drives the LPM ventral migration and commitment to an iSMC fate. Surprisingly, inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, suggesting a crucial role for this enzyme and nonmitochondrial CoQ10 in NO signaling. Angiogenesis, from the Greek blood vessels (angio) creation (genesis), is an important biological process that occurs both during health and disease. Nelle ultime ore è morto Massimo Santoro, il genero di Rita Dalla Chiesa. Non sono ore facili per Rita Dalla Chiesa e per la sua famiglia, colpita da un grave lutto che coinvolge anche la Rai. Massimo Santoro, morto all’età di 52 anni, era originario di Foggia ma viveva a Roma da molti anni. Here, the most recent methods and studies on cell metabolism are summarized, which support the overall value for the zebrafish model system not only to study metabolism but also metabolic disease states. In 2017, he returned to Italy at University of Padua as Chair of Cell Biology at Department of Biology. Massimo’s goal is to expand the current vision of endothelial biology by identifying unforeseen metabolic and signaling mechanisms and used them to develop novel anti-angiogenesis therapies to treat cancer progression and diabetic conditions. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Detecting and measuring the dynamic redox events that occur in vivo is a prerequisite for understanding the impact of oxidants and redox events in normal and pathological conditions. Precise morphogenetic and cellular mechanisms act in endothelial cells (ECs) to drive angiogenesis during growth and throughout adulthood. PROUDLY CREATED WITH WIX.COM, Department of Biology, University of Padua, Italy. We identify a pathway, comprising the regulators of post-Golgi carrier formation PI4KB and AP-1A, the small GTPase Rab11B, the surface tyrosine phosphatase receptor PTPRF and its adaptor PPFIA1, which we propose acts as a funnel combining FN secretion and recycling of active α5β1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis. Generale 3758 Mar. Sia il 2017 che il 2018, infatti, sono stati caratterizzati da dolorose assenze. 'Massimo ha lottato fino all'ultimo e Giulia con lui. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. The past few years have seen the zebrafish system emerge as a valid model organism to study developmental angiogenesis and, more recently, as an alternative vertebrate model for cancer research. Il saluto commovente di Uno Mattina a Massimo Santoro. Learn more about our team and areas of study below. We foresee the zebrafish model as an important system that can possibly complement well-established mouse models in cancer research to generate novel insights into the molecular mechanism of the tumor angiogenesis. We show that PPFIA1 is required for FN polymerization-dependent vascular morphogenesis, both in vitro and in the developing zebrafish embryo. His lab is currently focused on studying how redox signaling, metabolism, and hemodynamic forces regulates endothelial homeostasis in development as well as during cancer progression. Massimo Santoro si è spento lo scorso mese di novembre dopo aver lottato insieme a sua moglie in una lunga malattia. A key question in vascular biology is how the diversity of origin of vascular mural cells, namely smooth muscle cells and pericytes influences vessel properties, in particular the regional propensity to vascular diseases. CILIA CONTROL VASCULAR MURAL CELL RECRUITMENT IN VERTEBRATES. We hypothesized a novel autosomal recessive condition. Nuovo lutto per la famiglia di Rita Dalla Chiesa. Vascular mural cells (vMCs) are essential components of the vertebrate vascular system, controlling blood vessel maturation and homeostasis. ROLE OF AMINO ACID METABOLISM IN ANGIOGENESIS. Excellent communication skills in spoken and written English are required. Dai geni alla terapia: nuovi farmaci antitumorali. Recent advances arising from in vitro strategies for deriving mural cells from human pluripotent stem cells as well as from the zebrafish model will be discussed and the medical relevance of these discoveries will be highlighted. This review outlines the metabolic-dependent mechanisms that tumors engage in when faced with oxidative stress conditions that are critical for cancer progression by producing redox cofactors. We combine genetic and metabolic approaches coupled to advance imaging techniques to address specific biological questions and develop new therapeutic approaches. View Massimo Santoro’s profile on LinkedIn, the world's largest professional community. DATA ON METABOLIC-DEPENDENT ANTIOXIDANT RESPONSE IN THE CARDIOVASCULAR TISSUES OF LIVING ZEBRAFISH UNDER STRESS CONDITIONS. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Prima di affrontare il problema dell’abuso e del maltrattamento è opportuna una premessa su cosa vuol dire fare e come è stata fatta la storia dell’infanzia. BLOOD FLOW CONTROLS BONE VASCULAR FUNCTION AND OSTEOGENESIS. Since this idea has major implications for understanding and modelling human disease, then there is a pressing need for new model systems to investigate mural cell development and the consequences of heterogeneity. During his career, he has been granted with the EMBO (2004) and HFSP (2005) long-term fellowships, the HFSP Career Developmental Award (2008), the Marie Curie Reintegration Grant (2010), the Odysseus-FWO Career Grant (2014), and, more recently, the ERC Consolidator Grant (2016). Massimo Mattia Santoro obtained is Master Diploma from University of Turin, Italy and his PhD in Molecular and Cellular Biology from the Open University, London, UK. A novembre dello scorso anno è venuto a mancare Massimo Santoro, marito della figlia di Rita, Giulia Cirese. Massimo Mattia Santoro obtained is Master Diploma from University of Turin, Italy and his PhD in Molecular and Cellular Biology from the Open University, London, UK. In two siblings, a male and female, we identified an undescribed type of lethal congenital restrictive cardiomyopathy affecting the right ventricle. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. In 2008, he established his first independent laboratory at the University of Torino, opening the Molecular Biotechnology Center. AN EXCLUSIVE CELLULAR AND MOLECULAR NETWORK GOVERNS INTESTINAL SMOOTH MUSCLE CELL DIFFERENTIATION IN VERTEBRATES. Then he moved as post-doctoral fellow to the University of California, San Francisco, USA, where he became interested in vascular development and in health and diseased angiogenesis. Highly recommended as a CTO for startup-type enterprises. Rita Dalla Chiesa ricorda il genero Massimo Santoro, morto alcuni mesi fa.

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