Fondation MEDIC

www.fondation-medic.ch

Epigenetic mechanisms in the development of pediatric tumors
[10.11.2016]
Project leader – Nicolò Riggi
Nicolò Riggi

Physician-scientist specialized in pediatric tumors, Nicolò Riggi has been nominated Bursary Assistant Professor FNS at the Institute of Pathology at the CHUV Hospital in Lausanne, starting May 1st 2015. His work aims to decipher molecular mechanisms involved in the initiation of different pediatric cancers. In particular, he is interested in epigenetic regulatory networks controlling cellular differentiation state and biological aggressiveness of these tumors.

Nicolò Riggi was born in Switzerland in 1974, and earned his MD and MD-PhD at the University of Lausanne in 2001 and 2009, respectively. Between 2002 and 2009, he trained in molecular cancer biology at the Institute of Pathology in Lausanne, under the supervision of his mentor, Prof. Ivan Stamenkovic. His research focused on the cell of origin of different pediatric sarcomas, particularly Ewing Sarcoma, the second most frequent malignant bone tumor in the pediatric population. His work received several prestigious awards, including the « lnvestigator-in-training Award » from the l’UNIL. After the obtention of his MD-PhD in 2009, Nicolò Riggi pursued his clinical training in Pathology at the CHUV until 2011.

In 2011, Nicolò Riggi obtained a FNS and Oncosuisse Grant allowing him to join the research and clinical groups of Prof Petur. G. Nielsen, Miguel N. Rivera and Bradley. E. Bernstein at the Massachusetts General Hospital and Broad Institute in Boston. During four years he followed intense training in Clinical Pathology of pediatric tumors, while in parallel performing some seminal work in the field of epigenetics in sarcomas. Following this training period, Nicolò Riggi was awarded of a Professorship FNS Grant, and started his own research laboratory in Lausanne.

Division of Experimental Pathology

University Institute of Pathology
The Riggi Laboratory

Rue du Bugnon 25

1005 Lausanne Switzerland

E-Mail: Nicolo.Riggi@unil.ch
Phone: +41 21 314 71 11

Group members
 

Ram Mohan P R

post-doctoral fellow

Sanalkumar Subhadra

post-doctoral fellow

Liliane Gonzalez

PhD student

Arnaud Bakaric

MD-PhD student

Beverly Naigles

Lab Technician (MGH Cancer Center)

Project description
 

The Riggi Laboratory at the Institute of Pathology in Lausanne-CHUV
The Riggi Laboratory is focused on the identification of the epigenetic mechanisms driving malignant transformation, as well as intratumoral heterogeneity in pediatric tumors. The recent wealth of genomic sequencing studies has shed light on the presence of key biological differences between adult and pediatric cancers. Whereas the development of adult tumors frequently rely on the stepwise accumulation of genetic alterations, pediatric tumors are almost invariably initiated by a very limited number of genetic events, frequently in the form of single balanced chromosomal translocations. Pediatric tumors, therefore, represent a very different biological entity, driven by specific and unique oncogenic events, leading to a massive deregulation of cellular differentiation, proliferation, and ultimately malignant transformation. The Riggi’s laboratory is particularly interested in understanding the initial deregulation of epigenetic transcriptional programs allowing the transformation of permissive cell of origin, and the subsequent development of intratumoral heterogeneity. To this aim we analyze the epigenetic landscape and regulatory networks of several pediatric tumors, that are driven by a single genetic event. The first research axis aims to decipher the biological impact of tumor-specific translocations on gene expression profiles and tumorigenic properties in Desmoplastic Round Cell Tumor and Synovial Sarcoma. The second line of research is focused on the identification of the epigenetic determinants of clinical and molecular heterogeneity in Neuroblastoma. The Riggi’s group utilize a translational approach involving several national and international collaborations, facilitating the access to cutting-edge technologies and the rapid bench-to-bed translation of the most relevant and clinical impactful findings.

Publications
 
2014 / 10.1158/0008-5472.CAN-14-1106
Cornaz-Buros S, Riggi N, DeVito C, Sarre A, Letovanec I, Provero P, Stamenkovic I. Targeting cancer stem-like cells as an approach to defeating cellular heterogeneity in Ewing sarcoma. Cancer Res. 2014 Nov 15;74(22):6610-22
» PubMed
2014 / 10.1016/j.ccell.2014.10.004
Riggi N, Knoechel B, Gillespie SM, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell. 2014 Nov 10;26(5):668-81
» PubMed
2013 / 10.1126/science.1230184
Suvà ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science. 2013 Mar 29;339(6127):1567-70
» PubMed
2012 / 10.1101/gad.188292.112
Janiszewska M, Suvà ML, Riggi N, Houtkooper RH, Auwerx J, Clément-Schatlo V, Radovanovic I, Rheinbay E, Provero P, Stamenkovic I. Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes Dev. 2012 Sep 1;26(17):1926-44
» PubMed
2012 / 10.1016/j.ccr.2012.04.023
De Vito C, Riggi N, Cornaz S, Suvà ML, Baumer K, Provero P, Stamenkovic I. A TARBP2-dependent miRNA expression profile underlies cancer stem cell properties and provides candidate therapeutic reagents in Ewing sarcoma. Cancer Cell. 2012 Jun 12;21(6):807-21
» PubMed
2011 / 10.1586/era.10.235
Riggi N, Suvà ML, Stamenkovic I. The cancer stem cell paradigm in Ewing's sarcoma: what can we learn about these rare cells from a rare tumor?. Expert Rev Anticancer Ther. 2011 Feb;11(2):143-5
» PubMed
2011 / 10.1371/journal.pone.0023592
DeVito C, Riggi N, Suvà ML, Janiszewska M, Horlbeck J, Baumer K, Provero P, Stamenkovic I. Let-7a is a direct EWS-FLI-1 target implicated in Ewing’s sarcoma development. PLoSONE, 2011, 6:e23592
» PubMed
2010 / 10.1101/gad.1899710
Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L, Janiszewska M, Petricevic T, Suvà D, Tercier S, Joseph JM, Guillou L, Stamenkovic I. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010, 24:916-932
» PubMed
2009 / 10.1158/0008-5472.CAN-09-1622
Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 2009, 69:2911-2918
» PubMed
2009 / 10.1158/0008-5472.CAN-08-2242
Suvà ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, Suvà D, Clément V, Provero P, Cironi L, Osterheld MC, Guillou L, Stamenkovic I. Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res. 2009, 69:1776-1781
» PubMed