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Targeting diseased epigenomes by tuning mitochondrial metabolism

Event Details:

  • Date: - -
  • Venue: Collegio A Volta, Pavia
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Carlo Gaetano of the Istituti Clinici Scientifici Maugeri (Pavia) will give a seminar on Monday the 8th of October in the lecture theatre of Collegio A Volta (17, via A Ferrata) at 5.00 pm.  The  seminar, entitled Targeting diseased epigenomes by tuning mitochondrial metabolism, will discuss recent work by the speaker in analysing the epigenetic footprints that define several human diseases, notably diabetes.  The poster of the lecture can downloaded here.  Students of Biology, Biotechnology and Medicine Courses as well as members of Collegio A Volta and members of the Department of Molecular Medicine are strongly encouraged to attend.

Abstract
The first part of the presentation will describe the recently published outcome of an integrated metabolomics, transcriptomic and genomicapproach carried out in order to better understand the origin of epigenetic alteration evident in human primary cardiac stromal cells obtained from diabetic patients undergoing cardiac surgery. This research, conducted in collaboration with other Institutions in Europe, USA, and Australia, led to the characterisation of new small molecules targeting specific mitochondrial metabolic/epigenetic pathways controlling enzymes involved in DNA methylation. The second part of my talk will present unpublished data about a new role for P300/CBP associated factor (PCAF) in regulating mitochondria acetylation and function during skeletal muscle differentiation.

Biography
C Gaetano heads a newly established Laboratory of Epigenetics at Istituti Clinici Scientifici Maugeri in Pavia (Italy). During his training he was Fogarty Fellow and Associate at the National Cancer Institute in the Molecular Genetics Section of the Pediatric Branch from 1989 until 1992, Bethesda (USA). He was a Visiting Scientist of the National Cancer Institute form may 1995 to September 1996 and then Visiting Associate Professor at McMaster University, Hamilton (CA) in 1999. From 1997 to 2012 he was Senior Scientist and Group Leader at the Laboratorio di Patologia Vascolare of the “Istituto Dermopatico dell’Immacolata-IRCCS”. From May 2012 until December 2017 he was Professor of stem cell epigenetics and Director of the Division of Cardiovascular Epigenetics at the Department of Cardiology, Faculty of Medicine, Goethe University, Frankfurt-am-Main (DE). His major scientific interest throughout the years has been epigenetics applied to clinically relevant diseases. In recent years, hid laboratory established in vitro and in vivo human disease models with special attention to human primary cells isolated from volunteer donors including human cardiac stromal cells from non-diabetic and diabetic patients. The studies focused on the epigenetic consequences of environmental challenges (e.g. high glucose, UV radiation, chemicals) causing mitochondrial metabolic alterations and their effect on DNA conformation, integrity and function. Together with other Institutions in Europe and US, he is also characterising new small molecules targeting DNA methylation including DNA methyltransferases (DNMTs) and Ten-eleven-translocation (TET) enzymes.

Reference
Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by alpha-Ketoglutarate and TET-TDG Functional Reactivation. Spallotta, F. et al. Stable. Circulation Research 122, 31-46, 2018.

Image
Courtesy of E Heard, Institut Curie, Paris, France

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