MedInTO Medicine and Surgery

ADE - CEREBROVASCULAR MALFORMATIONS: PATHOGENETIC MECHANISM AND THERAPEUTIC STRATEGIES

Ade - Cerebrovascular malformations: pathogenetic mechanism and therapeutic strategies

Academic year 2020/2021

Sommario del corso

• Course objectives
• Results of learning outcomes
• Course delivery
• Learning assessment methods
• Program
• Suggested textbooks and readings
• Notes
• Teaching tools

Course objectives

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Results of learning outcomes

-

Course delivery

Webex lectures/seminars

Learning assessment methods

-

Program

Elective Didactic Activity (EDA/ADE)
Cerebrovascular malformations: pathogenic mechanisms and therapeutic strategies

27/04/2021

• 9:30-10:00  Prof. Saverio Francesco Retta (Applied Biology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
  Introduction to the webinars
• 10:00-11:00  Prof. Chris Sobey (Vascular Biology) (Centre for Cardiovascular Biology, La Trobe University, Melbourne, Australia)
  Targeting inflammation-induced injury in stroke
• 11:00-12:00  Prof. Marco Fontanella (Neurosurgery) (Department of Surgical Specialties, University of Brescia, Italy)
  Clinical and neurosurgical features of Cerebral Cavernous Malformation (CCM) disease
• 17:00-18:00  Prof. Angela Glading (Cell Biology) (Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA)
  KRIT1/CCM1: A master regulator of endothelial quiescence

28/04/2021

• 10:00-11:00  Prof. Saverio Francesco Retta (Applied Biology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
  From genes to targeted therapies: the long climb to the cure of Cerebral Cavernous Malformation (CCM) disease
• 11:00-12:00  Dr. Raffaella Mastrocola (General Pathology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
  Metabolic impact of KRIT1/CCM1 mutation predisposing to Cerebral Cavernous Malformations: a possible role for Advanced Glycation End-products?
• 16:00-17:00  Dr. Andrea Perrelli (Applied Biology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
  Towards precision nanomedicine for Cerebral Cavernous Malformation (CCM) disease
• 17:00-18:00  Prof. Jun Zhang (Molecular Medicine) (Department of Molecular and Translational Medicine, Texas Tech University, El Paso, TX, USA)
  A new therapeutic strategy for hemorrhagic Cerebral Cavernous Malformations (CCMs)

29/04/2021

• 10:00-11:00  Dr. Souvik Kar (Molecular Biology) (International Neuroscience Institute, Hannover, Germany)
  Non-coding RNA repertoires in Cerebral Cavernous Malformations: identification and role in disease pathogenesis
• 11:00-12:00  Prof. Giovanni Battista Ferrero (Clinical Genetics) (Department of Clinical and Biological Sciences, University of Torino)
  The potential of Next-Generation Sequencing (NGS) technology: comprehensive whole-genome and whole-exome profiling to identify genetic variants
• 12:00-13:00  Dr. Valerio Benedetti (Applied Biology) (Department of Clinical and Biological Sciences, University of Torino)
  Next-Generation Sequencing (NGS) Strategies for Genetic Testing of Cerebral Cavernous Malformation (CCM) Disease
• 16:00-17:00  Dr. Eva Faurobert (Cellular Biology) (French National Centre for Scientific Research, Paris, France)
  Role of mechanotransduction in the pathogenesis of Cerebral Cavernous Malformations: molecular and cellular aspects
• 21:00-22:00  Prof. Kelly Flemming (Neurology) (Mayo Clinic, Rochester, MN, USA)
  Clinical Presentation and Management of Cerebral Cavernous Malformations

1. Perrelli A, Fatehbasharzad P, Benedetti V, Ferraris C, Fontanella M, De Luca E, Moglianetti M, Battaglia L, Retta SF. (2021). Towards precision nanomedicine for cerebrovascular diseases with emphasis on Cerebral Cavernous Malformation (CCM). Expert Opinion on Drug Delivery. 2021 Jan 23:1-28. doi:10.1080/17425247.2021.1873273.
2. Kim AH, Perrelli A, Ragni A, Retta F, De Silva TM, Sobey GC, Retta SF*. (2020). Vitamin D Deficiency and the Risk of Cerebrovascular Disease. Antioxidants (Basel). 2020 Apr 17; 9(4), pii: E327; doi:10.3390/antiox9040327.
3. Retta SF, Perrelli A, Trabalzini L, Finetti F. (2020). From Genes and Mechanisms to Molecular-Targeted Therapies: The Long Climb to the Cure of Cerebral Cavernous Malformation (CCM) Disease. Methods Mol Biol. 2020;2152:3-25. doi: 10.1007/978-1-0716-0640-7_1.
4. Antognelli C, Perrelli A, Armeni T, Nicola Talesa V, Retta SF*. (2020). Dicarbonyl Stress and S-Glutathionylation in Cerebrovascular Diseases: A Focus on Cerebral Cavernous Malformations. Antioxidants (Basel). 2020 Feb 1; 9(2). pii: E124. doi: 10.3390/antiox9020124.
5. Vieceli Dalla Sega F, Mastrocola R, Aquila G, Fortini F, Fornelli C, Zotta A, Cento AS, Perrelli A, Boda E, Pannuti A, Marchi S, Pinton P, Ferrari R, Rizzo P, Retta SF*. (2019). KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction. Int J Mol Sci. 2019 Oct 5; pii: E4930. doi:c10.3390/ijms20194930.
6. Cianfruglia L, Perrelli A, Fornelli C, Magini A, Gorbi S, Salzano AM, Antognelli C, Retta F, Benedetti V, Cassoni P, Emiliani C, Principato G, Scaloni A, Armeni T, Retta SF*. (2019). KRIT1 Loss-Of-Function Associated with Cerebral Cavernous Malformation Disease Leads to Enhanced S-Glutathionylation of Distinct Structural and Regulatory Proteins. Antioxidants (Basel). 2019 Jan 17;8(1):1-28.
7. De Luca E, Pedone D, Moglianetti M, Pulcini D, Perrelli A, Retta SF* & Pompa PP (2018). Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation. ACS Omega, 2018 Nov 30;3(11):15389-15398.
8. Perrelli A, Goitre L, Salzano AM, Moglia A, Scaloni A, and Retta SF*. (2018). Biological Activities, Health Benefits, and Therapeutic Properties of Avenanthramides: From Skin Protection to Prevention and Treatment of Cerebrovascular Diseases. Oxidative Medicine and Cellular Longevity 2018, 6015351.
9. Antognelli C, Trapani E, Delle Monache S, Perrelli A, Daga M, Pizzimenti S, Barrera G, Cassoni P, Angelucci A, Trabalzini L, Talesa VN, Goitre L, Retta SF*. (2018). KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: Implication for Cerebral Cavernous Malformation disease. Free Radical Biology and Medicine 2018 Feb 1; 115:202-218. Epub 2017 Nov 21.
10. Antognelli C, Trapani E, Delle Monache S, Perrelli A, Fornelli C, Retta F, Cassoni P, Talesa VN, Retta SF*. (2017). Data in support of sustained upregulation of adaptive redox homeostasis mechanisms caused by KRIT1 loss-of-function. Data Brief. 2017 Dec 13; 16:929-938.
11. Goitre L, DiStefano PV, Moglia A, Nobiletti N, Baldini E, Trabalzini L, Keubel J, Trapani E, Shuvaev VV, Muzykantov VR, Sarelius IH, Retta SF* & Glading AJ. (2017). Up-regulation of NADPH oxidase-mediated redox signaling contributes to the loss of barrier function in KRIT1 deficient endothelium. Scientific Reports, 2017 Aug 15; 7(1):8296.
12. Retta SF* and Glading AJ. (2016). Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin. International Journal of Biochemistry & Cell Biolology. 2016 Dec; 81(Pt B):254-270.
13. Marchi S, Trapani E, Corricelli M, Goitre L, Pinton P, Retta SF*. (2016). Beyond Multiple Mechanisms and a Unique Drug: Defective Autophagy as Pivotal Player in Cerebral Cavernous Malformation Pathogenesis and Implications for Targeted Therapies. Rare Diseases, 2016 Jan 25; 4:1, e1142640.
14. Marchi S, Retta SF*, Pinton P. (2016). Cellular processes underlying cerebral cavernous malformations: Autophagy as another point of view. Autophagy, 2016 Feb; 12(2):424-5.
15. Moglianetti M, De Luca E, Pedone D, Marotta R, Catelani T, Sartori B, Amenitsch H, Retta SF, Pompa PP. (2016). Platinum nanozymes recover cellular ROS homeostasis in oxidative stress-mediated disease model. Nanoscale, 2016 Feb 14; 8(6):3739-52.
16. Choquet H, Trapani E, Goitre L, Trabalzini L, Akers A., Fontanella M, Hart BL, Morrison LA, Pawlikowska L, Kim H, Retta SF*. (2016). Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1. Free Radical Biology and Medicine, 2016 Jan 19; 92:100-109.
17. Marchi S, Corricelli M, Trapani E, Bravi L, Pittaro A, Delle Monache S, Ferroni L, Patergnani S, Missiroli S, Goitre L, Trabalzini L, Rimessi A, Giorgi C, Zavan B, Cassoni P, Dejana E, Retta SF*, Pinton P. (2015). Defective autophagy is a key feature of cerebral cavernous malformations. EMBO Molecular Medicine, 2015. 7(11):1403-1417.
18. Trapani E, Retta SF*. (2015). Cerebral cavernous malformation (CCM) disease: from monogenic forms to genetic susceptibility factors. Journal of Neurosurgical Sciences, 2015 Sep; 59(3):201-9.
19. Gibson C., Zhu W., Davis C.T., Bowman-Kirigin J.A., Chan A.C., Ling J., Walker A.E., Goitre L., Delle Monache S., Retta S.F., Shiu Y-T E., Grossmann A.H., Thomas K.R., Donato A.J., Lesniewski L.A., Whitehead K.J., Li D.J. (2015) Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation. Circulation, 2015; 131(3):289-99.
20. Fontanella MM, Panciani PP, Spena G, Roca E, Migliorati K, Ambrosi C, Sturiale CL, Retta SF (2015) Professional athletes and cerebral cavernomas: an obstacle to overcome. Journal of Sports Medicine and Physical Fitness, 2015 Sep; 55(9):1046-7.
21. Goitre L, De Luca E, Braggion S, Trapani E, Guglielmotto M, Biasi F, Forni M, Moglia A, Trabalzini L, Retta SF*. (2014) KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun. Free Radical Biology and Medicine, 2014 Mar; 68:134-47.
22. Maddaluno L, Rudini N, Cuttano R, Bravi L, Giampietro C, Corada M, Ferrarini L, Orsenigo F, Papa E, Boulday G, Tournier-Lasserve E, Chapon F, Richichi C, Retta SF, Lampugnani MG, Dejana E. (2013) EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature,2013; 498(7455):492-6.
23. Bacigaluppi S, Retta S.F., Pileggi S, Fontanella M, Goitre L, Tassi L, La Camera A, Citterio A, Patrosso MC, Tredici G, Penco S. (2013) Genetic and cellular basis of Cerebral Cavernous Malformations: implications for clinical management. Clinical Genetics, 2013; 83(1):7-14.
24. D’Angelo R., Marini V., Rinaldi C., Origone P., Dorcaratto A., Avolio M., Goitre L., Forni M., Capra V., Alataci C., Mareni C., Garrè C., Bramanti P., Sidoti A., Retta S.F.*, Amato A. (2011). Mutation Analysis of CCM1, CCM2 and CCM3 Genes in a Cohort of Italian Patients with Cerebral Cavernous Malformation. Brain Pathology, 2011; 21(2): 215–224.
25. Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P., Retta S.F.* (2010). KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species. PLoS One, 2010; 5(7):e11786.

Class schedule

Note

Maximum number of students: 40

• Teaching materials
• Exams and finals
• Go to Moodle
• Visit the forums