PHD Course Pardi (3)

UniSR Graduate School of Molecular Medicine
Cell & Molecular Biology track
One-week course on:
Cell Biology of Disease
An overview and representation of basic discoveries stemming from medical
needs and potentially leading to therapeutic applications
June 30th thru July 4th, 2014
(local organizer: Ruggero Pardi; [email protected])
Aim of this Course is to provide examples of how unsolved health needs in clinical
medicine can lead to major basic discoveries that in turn provide insights into novel therapeutic
approaches. This process is commonly referred to as "translational" research. This workshop,
however, will place emphasis on the basic biological processes unveiled through in-depth
dissection of ill-defined etiological or pathogenic issues in diseases as diverse as cancer, periodic
fever and muscular dystrophy.
The educational goals of this course are two-fold: on the one hand, students should
deepen their knowledge of defined fundamental processes in cell and molecular biology, both by
reading the assigned material and by being exposed to the scientific background and rationale of
the studies presented during the course; on the other hand, students should be given examples
of how a clinical problem (e.g. unexplained fever, relapse of a tumor, muscle weakness) can be
deciphered and eventually explained in mechanistic terms, which is the realm of molecular
pathogenesis.
The structure of the course is based on five "one-day" modules comprising a morning
lecture by a distinguished scientist addressing pathogenic issues in human disease, followed by a
journal club session discussing contributions by the lecturer's group or by their competitors.
Piccolo's work addresses the pathogenic role of tumor-initiating cells in clinical settings such as
tumor latency, dormancy and recurrence. He will discuss the role of the transcriptional coregulators YAP/TAZ in the pathophysiology of tissue homeostasis. Di Virgilio will present data
addressing the role of purinergic receptors and the inflammasomes in the molecular
pathogenesis of periodic fever. Di Fiore and Pece will discuss their findings suggesting that breast
cancer stem cells share features with normal mammary epithelial stem cells and are a marker of
tumors endowed with a poorer prognosis. Tupler will show how a careful genetic
characterization of a hereditary disease (FSHD) can give insights into its molecular pathogenesis.
Finally, De Matteis will again demonstrate how identifying the genetic basis of a rare disease is
invaluable to clarify its molecular pathogenesis.
***
Required knowledge base to appraise the biological foundations of the main topics to be
covered by the course: (1) basic mechanisms of gene expression regulation (transcriptional and
post-transcriptional control), as can be read e.g. in Chapters 6 & 7 of the 2008 edition of Albert's
Molecular Biology of the Cell; (2) generals on cell-cell communication and signal transduction,
with emphasis on the role of receptors, adaptors, transducers and effectors in signals originating
from the plasma membrane (e.g. Chapter 15 of 2008 Albert's Molecular Biology of the Cell); (3)
structure-function of the exocytic compartment and principles of protein sorting (e.g Chapters
12 & 13 of 2008 Albert's Molecular Biology of the Cell).
Course Program
Monday June 30th, 2014
10:50-11:00
Ruggero Pardi
Introduction to the Course
11:00-12:30
Stefano Piccolo (PD)
YAP/TAZ: Organ size control, stem cells
and cancer
14:00-16:00
Journal Club Session
Piccolo JC1 or JC2
Tuesday July 1st, 2014
11:00-12:30
Francesco Di Virgilio (FE)
Extracellular ATP is the prototypic proinflammatory DAMP (DamageAssociated Molecular Pattern)
14:00-16:00
Journal Club Session
Di Virgilio JC1 or JC2
Wednesday July 2nd, 2014
11:00-12:30
Pier Paolo Di Fiore and
Salvatore Pece (MI)
Fate determination and tumor suppression
in stem cells
14:00-16:00
Journal Club Session
Di Fiore & Pece JC1 AND JC2
Thursday July 3rd, 2014
11:00-12:30
Rossella Tupler (MO)
Facioscapolohumeral muscular
dystrophy: how a hereditary disease
can change the life of a medical
geneticist
14:00-16:00
Journal Club Session
Tupler JC1 or JC2
Friday July 4th, 2014
11:00-12:30
Antonella De Matteis (NA)
What we can learn from genetic
disorders of membrane trafficking
14:00-16:00
Journal Club Session
De Matteis JC1 or JC2
Students Assignments
PICCOLO Review
Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Halder G, Dupont S, Piccolo S.
Nat Rev Mol Cell Biol. 2012 Sep;13(9):591-600.
PMID: 22895435
PICCOLO JC1
The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer
cells.Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M,
Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S. Cell. 2011 Nov
11;147(4):759-72.
PMID: 22078877
PICCOLO JC2
Role of YAP/TAZ in mechanotransduction. Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S,
Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S. Nature.
2011 Jun 8;474(7350):179-83.
PMID: 21654799
DI VIRGILIO Review
The therapeutic potential of modifying inflammasomes and NOD-like receptors. Di Virgilio F.
Pharmacol Rev. 2013 Apr 16;65(3):872-905.
PMID: 23592611
DI VIRGILIO JC1
K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and
particulate matter. Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM, Núñez
G. Immunity. 2013 Jun 27;38(6):1142-53.
PMID: 23809161
DI VIRGILIO JC2
The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination.
Vono M, Taccone M, Caccin P, Gallotta M, Donvito G, Falzoni S, Palmieri E, Pallaoro M, Rappuoli R,
Di Virgilio F, De Gregorio E, Montecucco C, Seubert A. Proc Natl Acad Sci U S A. 2013 Dec
24;110(52):21095-100.
PMID: 24324152
DI FIORE & PECE Review
NUMB-ing down cancer by more than just a NOTCH. Pece S, Confalonieri S, R Romano P, Di Fiore
PP. Biochim Biophys Acta. 2011 Jan;1815(1):26-43.
PMID: 20940030
DI FIORE & PECE JC1
Distinct stem cells contribute to mammary gland development and maintenance.
Van Keymeulen A1, Rocha AS, Ousset M, Beck B, Bouvencourt G, Rock J, Sharma N, Dekoninck
S, Blanpain C. Nature. 2011 Oct 9;479:189-93.
PMID: 21983963
DI FIORE & PECE JC2
In situ identification of bipotent stem cells in the mammary gland. Rios AC, Fu NY, Lindeman
GJ, Visvader JE. Nature. 2014 Feb 20;506:322-7.
PMID: 24463516
TUPLER Review
The cell biology of disease: FSHD: copy number variations on the theme of muscular dystrophy.
Cabianca DS, Gabellini D. J Cell Biol. 2010 Dec 13;191(6):1049-60.
PMID: 21149563
TUPLER JC1
Large scale genotype-phenotype analyses indicate that novel prognostic tools are required for
families with facioscapulohumeral muscular dystrophy. Ricci G, Scionti I, Sera F, Govi M, D'Amico
R, Frambolli I, Mele F, Filosto M, Vercelli L, Ruggiero L, Berardinelli A, Angelini C, Antonini G, Bucci
E, Cao M, Daolio J, Di Muzio A, Di Leo R, Galluzzi G, Iannaccone E, Maggi L, Maruotti V, Moggio M,
Mongini T, Morandi L, Nikolic A, Pastorello E, Ricci E, Rodolico C, Santoro L, Servida M, Siciliano G,
Tomelleri G, Tupler R. Brain. 2013. 136:3408-17.
PMID: 24030947
TUPLER JC2
A unifying genetic model for facioscapulohumeral muscular dystrophy. Lemmers RJ, van der Vliet
PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, Snider L, Straasheijm KR, van Ommen GJ,
Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM. Science. 2010 Sep
24;329:1650-3.
PMID: 20724583
DE MATTEIS Review
Mendelian disorders of membrane trafficking. De Matteis MA, Luini A. N Engl J Med. 2011 Sep
8;365(10):927-38.
PMID: 21899453
DE MATTEIS JC1
OCRL controls trafficking through early endosomes via PtdIns4,5P₂-dependent regulation of
endosomal actin. Vicinanza M, Di Campli A, Polishchuk E, Santoro M, Di Tullio G, Godi A,
Levtchenko E, De Leo MG, Polishchuk R, Sandoval L, Marzolo MP, De Matteis MA. EMBO J. 2011
Oct 4;30(24):4970-85.
PMID: 21971085
DE MATTEIS JC2
Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. Venditti R, Scanu T,
Santoro M, Di Tullio G, Spaar A, Gaibisso R, Beznoussenko GV, Mironov AA, Mironov A Jr, Zelante
L, Piemontese MR, Notarangelo A, Malhotra V, Vertel BM, Wilson C, De Matteis MA. Science. 2012
Sep 28;337(6102):1668-72.
PMID: 23019651