Targeting Diseased Epigenomes by Tuning Mitochondrial Metabolism

8th October 2018.  
Carlo Gaetano, Istituti Clinici Scientici Maugeri, Pavia

On the 8th of October 2018 Carlo Gaetano, of the Istituti Clinici Scientifici Maugeri, will give a seminar on Targeting diseased epigenomes by tuning mitochondrial metabolism at 5.00 pm in the College lecture theatre. Epigenetics, namely the range of enzymatic and non-enzymatic DNA modifications that finely tune gene expression during development and tissue regeneration also play an important role in disease.  In his talk C Gaetano will address and discuss this latter area of research. All College students are invited to attend, especially those reading Medicine, Biology, Biotechnology and Pharmaceutical Sciences. The poster of the lecture can be downloaded here.

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 The second part of my talk will present unpublished data about a new role for P300/CBP associated factor (PCAF) in regulating mitochondria acetylation and function during skeletal muscle differentiation.

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.

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.

Courtesy of the Royal Society of Chemistry.


Challenging Therapies for Muscular Dystrophies

4th October 2018.  
Giulio Cossu, University of Manchester

On the 4th of October 2018 Giulio Cossu, of the University of Manchestterl, will give a seminar on Challenging therapies for muscular dysttrophies at 5.00 pm in the College lecture theatre. Muscular dysttrophies constitute an important group of diseases that have posed exceptional challenges to scientists and physicians. G Cossu will review progress and will highlight the major remaining challenges that have to be overcome in order to ensure successful therapy. All College students are invited to attend, especially thse reading Medicine, Biology, Biotechnology and Pharmaceutical Sciences. The poster of the lecture can be downloaded here.

In the last few years there has been significant advance in pre-clinical and clinical work of gene and cell therapy for muscular dystrophy. Currently there are several trials ongoing and more are expected to start. It is thus a time of expectation, even though many hurdles remain and it is unclear now whether they will be solved by current strategies or further improvements will be necessary. After reviewing current work in the field I will describe our current effort for an implemented protocol of cell therapy for muscular dystrophy. My laboratory has been working for many years on skeletal myogenesis and on the development of cell therapy protocols with stem cells for muscular dystrophy. We showed that neural tube (Vivarelli and Cossu, Dev. Biol. 1986) and dorsal ectoderm (Cossu et al., Development 1996) activate, through different Wnts, distinct myogenic programs in epaxial and hypaxial somitic progenitors. We also described myogenic cell heterogeneity (Cossu and Molinaro, Curr. Topics Dev. Biol. 1987) whose molecular basis has been recently elucidated (Messina et al. Cell 2010). We developed the first pre-clinical model for analysis of human myogenic progenitors in vivo (Salvatori et al., Hum Gene Ther. 1993), and discovered the myogenic potential of a bone-marrow derived, circulating progenitor cell (Ferrari et al., Science 1998). Our studies on unorthodox derivation of myogenic cells by non-somitic tissues (Tajbakhsh et al., Neuron 1994; Salvatori et al., J. Cell Sci. 1995) set the basis for the understanding of recruitment to myogenesis of non-myogenic cells, and the origin of multipotent mesoderm stem cells. We identified a mesoderm progenitor in the dorsal aorta (De Angelis et al. J Cell Biol. 1999), i.e. the mesoangioblast, able to contribute to mesoderm tissues upon transplantation (Minasi et al. Development 2002). Mesoangioblasts were used for the first successful cell therapy protocols of muscular dystrophy in mice and dogs (Sampaolesi et al. Science 2003; Nature, 2006). We characterized human mesoangioblasts as a subset of muscle pericytes (Dellavalle et al. Nature Cell Biol. 2007). Together, this data set the basis for a first clinical trial in Duchenne patients with stem cells (Cossu et al. EMBO Mol Med. 2015). We are currently optimising the protocol aiming at reaching clinical efficacy.

I am currently the Constance Thornley Professor of Regenerative Medicine at the University of Manchester. I received my MD degree from the University of Rome, then moved as Fogarty fellow at the University of Pennsylvania and in 1983 as Research Associate in Rome. In 1990 I spent an extended sabbatical at the Pasteur Institute in Paris. In 1992 I became Professor of Histology and Embryology in Rome. In 2000 I moved to Milan as Director of the Division of Regenerative Medicine at San Raffaele; in 2012 I moved as Professor of Human Stem Cell Biology to University College London and in 2013 to the University of Manchester. I began working as CAT member at EMA (2012-13). I am a member of EMBO, of the European Academy of Science, a fellow of the Academy of Medical Sciences and of Accademia dei Lincei. I am recognized for my work on muscle development and on cell therapy for muscular dystrophies. I have published more than 250 peer-reviewed papers and secured grants for more than15 M£

Section of skeletal muscle under the light microscope.

Matematica Generale

(Corsi di Laurea: Chimica, Chima e Tecnologie Farmaceutiche, Scienze Biologiche, Biotecnologie)


 Omar Najlani

01. Insiemi, intervalli, equazioni algebriche, disequazioni algebriche, trigonometria, geometria analitica nel piano
02. Grafico di una funzione reale, grafici e proprietà di alcune funzioni elementari, uomini delle funzioni più' comuni, funzioni composte
03. Funzioni elementari, teoremi sui limiti: teorema diunicita' del limite, teorema di permanenza del segno, teorema del confronto, operazioni sui limiti
04. Limiti notevoli, definizione di continuità', discontinuità' di prima, seconda e terza specie, teoremi sulle funzioni continue
05. Numeri complessi, forma algebrica dei numeri complessi, complesso coniugato, modulo e fase, rappresentazione in forma trigonometrica, formula di Eulero, rappresentazione in forma  esponenziale, formule di De Moivre, serie n, utilizzo, scale semi logaritcmicheumeriche, carattere della serie, alcune proprietà' serie notevoli, scale logaritmiche
06. Polinomi di Taylor, derivate, retta tangente, derivate fondamentali, regole di derivazione, monotonia e segno della derivata, massimi e minimi
07. Concavita' e derivata seconda, funzione convessa, funzione concava, punti di flesso, criterio della derivata seconda, teorema di Fermat, teorema di Lagrange, studio di funzione
08. Introduzione al calcolo integrale, integrale definito, proprietà' dell'integrale definito, funzioni primitive, integrale indefinito, integrali indefiniti immediati
09. Teorema di Torricelli-Barrow, teorema fondamentale del calcolo integrale, integrali impropri, integrazione per sostituzione, integrazione per parti
10. Problema di Cauchy, equazioni differenziali lineari del primo ordine, equazioni differenziali a variabili separabili, equazioni differenziali lineari del secondo ordine
11. Grafico per funzioni di due variabili, linee di livello, derivate parziali, gradiente, derivate direzionali, piano tangente al grafico di una funzione di due variabili, teorema di Schwartz
12. Riepilogo
13. Attendance


(Corsi di laurea:   Medicina e Chirugia - in lingua Inglese e Italiana, Scienze Biologiche, Biotecnologia, Molecular Biology and Genetics)

Fisiologia Umana A

(Corso di Laurea: Medicina e Chirurgia in lingua Italiana)


Valentina Carini

01. Fisiologia Cellulare 2. Vie nervose della sensibilità, Dolore
02. Fisiologia Gastroenterica 2. Secrezioni
03. Fisiologia Muscolare. Muscolo Scheletrico e Liscio, Contrazione Muscolare (isotonica e isometrica), Ciclo dei ponti trasversali
04. Fisiologia Cardiovascolare 1. Potenziale d’azione cardiaco, Elettrocardiografia
05. Fisiologia Cardiovascolare 3. Gittata Cardiaca, Metodi di calcolo della gittata, Controllo nervoso cardiaco, Recettori del sistema cardiovasale
06. Fisiologia Cardiovascolare 5. Circolazioni distrettuali
07. Fisiologia Renale 1. Anatomia del rene, Filtrazione, Clearance renale, Minzione
08. Fisiologia Renale 3. Controllo dell'osmolalità dei liquidi corporei
09. Fisiologia Renale 5. Controllo del volume dei liquidi corporei
10. Fisiologia del Sistema Respiratorio 1. Meccanica Respiratoria
11. Neurofisiologia 1. Controllo motorio e vie nervose
12. Neurofisiologia 3. Sonno, Sensi


Valentina Carini 

01. Fisiologia muscolare. Muscolo scheletrico e liscio; contrazione muscolare; ciclo dei ponti trasversali
02. Fisiologia cardiovascolare 1. Potenziale di azione cardiaco; elettrocardiografia
03. Fisiologia cardiovascolare 2. Meccanica Cardiaca
04. Fisiologia cardiovascolare 3. Gittata cardiaca; metodi di calcolo della gittata. Controllo nervoso cardiaco; recettori
05. Fisiologia cardiovascolare 4. Sistema vasale; controllo dei vasi del circolo sistemico
06. Fisiologia cardiovascolare 5. Circolazioni distrettuali
07. Fisiologia respiratoria 1. Meccanica respiratoria
08. Fisiologia respiratoria 2. Rapporto ventilazione-perfusione
09. Fisiologia respiratoria 3. Controllo nervoso
10. Fisiologia endocrina 1. Asse ipotalamo-ipofisario; tiroide
11. Fisiologia endocrina 2. Surrene
12. Fisiologia endocrina 3. Pancreas endocrino
13. Attendance

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