Our People

Biosketch
 
Professor Corrado Santocanale received his Ph.D. in Cellular and Molecular Biology at the University of Milan, Italy, in 1993. His early work focused on the characterization of enzymes required for the duplication of the DNA in the yeast S. cerevisiae. He was then awarded an EU Marie Curie postdoctoral fellowship to work on the molecular mechanisms that control initiation of DNA replication at the Clare Hall Laboratories, Cancer Research UK, London. He spent eight years in the pharmaceutical industry at the Oncology R&D site in Nerviano, Italy (former Pharmacia/Pfizer and now Nerviano Medical Sciences) both as a group and as a project leader developing protein kinase inhibitors for the treatment of human cancers. He has returned to academia in 2007 to pursue his studies.
In 2011 he was elected  in the council of the Irish Association for Cancer Research.
 

The major achievements in basic cancer research include:

  • Identification and characterization of the origin firing checkpoint, a biochemical pathway that is activated in response to the inhibition of DNA replication elongation thus preventing the activation of new replication origins.
  • Identification of the second cyclin like regulatory subunit of the human Cdc7 kinase.
  • The identification of a biochemical pathway, altered in cancer cells, responding to the inhibition of the Cdc7 kinase.
  • Identification of the gene encoding the first eukaryotic DNA primase large subunit.
The major achievement in Cancer Drug Discovery was to propose and lead a program through all the stages of the pre-clinical drug discovery process delivering a compound with a novel mechanism of action that is currently in clinical trials.

Education

October 1989-September 1993: Ph.D. degree in Cellular and Molecular Biology, University of Milan.
December 1988: University degree in Biology at the University of Milan with the highest rate (110/110 cum laude).      
             
Professional career
2004-2007 Principal Research Scientist and Project Leader. Nerviano Medical Sciences-Oncology, Nerviano, Italy.
2002-2004 Principal Research Scientist and Project Leader. Pfizer Oncology R&D, Nerviano, Italy
2000-2002 Principal Research Scientist and Project Leader. Pharmacia Corporation Oncology R&D, Nerviano, Italy
1999-2000 Research Scientist and Group leader, Pharmacia and Upjohn Oncology R&D, Nerviano, Italy
1994 to 1999: Post-doctoral fellow in the laboratory of Dr. John Diffley, ICRF (now Cancer Research UK) Clare Hall Laboratories, South Mimms, UK,
1993-1994: Postdoctoral fellow in the laboratory of Prof. Paolo Plevani and Prof. Giovanna Lucchini, University of Milan, funded by the University of Milan.
Research Interests

Research in my lab is centered on studying the mechanisms of DNA replication in cancer cells and exploiting the results of this research for therapeutic purposes. Active projects focus on understanding the cellular functions and regulation of Cdc7 kinase (A) and on characterizing inhibitors of Cdc7 kinase activity in Multiple Myeloma and Chronic Lymphocytic Leukaemia (B). Recently we have developed a technique that will allow us to study how chromatin assembly is coupled with the duplication of DNA (C).

A) Cdc7 acts as a molecular switch for DNA synthesis and is also thought to participate in several other processes that regulate normal cell cycle progression and chromosome dynamics. Human Cdc7 has two cyclin-like binding partners which form either a Cdc7/Dbf4 complex or a Cdc7/Drf1 complex-their reciprocal roles are not yet defined. Biochemical, structural and functional approaches are employed to characterize the role of human Cdc7. Specific goals are:

  • Define reciprocal roles of the Dbf4 and Drf1 regulatory subunits
  • Identify new roles/substrates of the kinase
  • Determine the structure of kinase active site and other structural domains
  • Determine the impact of miRNA on Cdc7 activity

Key to these projects is the access to a MS/proteomic facility. A great effort was put into the development of in house infrastructure that can currently support both protein ID and phosphosite ID. This resource and protocols are made available to NUIG researchers.

B) Cdc7 inhibitors have shown antitumor activity in broad spectrum of preclinical cancer models including solid and leukemia xenografts, carcinogen induced and transgenic models. Phase I clinical studies are ongoing. A key question for this new class of drugs is to identify those cancer types in which they may be more efficacious. Together with Micheal O'Dwyer (Prof. of Hematology and Hospital consultant) we have been testing the activity and mechanism of action of Cdc7 inhibitors in cells from MM and CLL patents. Cellular co-culture systems that mimic the protective microenvironment niche of the lymph nodes have been developed for this purpose.

C) Replication of DNA and duplication of the epigenetic information are critical to the transmission of the genetic material from the parental cell to the two daughter cells and for specifying cell-type identity of the two daughter cells.  To investigate how these processes are regulated and coordinated, it is important to determine the identity of the proteins that are either stably or transiently associated with newly synthesized DNA. We have devised an experimental procedure that allows newly synthesized chromatin to be efficiently captured and analyzed. We have termed this DNA mediated chromatin pull-down (Dm-ChP). Dm-ChP is a highly specific and flexible technique. Current work is focused on identifying the protein component of newly synthesized chromatin and in assessing qualitative and quantitative changes in this protein fraction caused by the normal temporal program of DNA replication as well as by perturbation of the DNA replication machinery.

Key Publications
Barkley LR, Santocanale C.
Oncogenesis. 2013 Jul 22;2:e57. doi: 10.1038/oncsis.2013.20.
PMID: 23877787 [PubMed] Free PMC Article
 
Rainey MD, Harhen B, Wang GN, Murphy PV, Santocanale C.
Cell Cycle. 2013 May 15;12(10):1560-8. doi: 10.4161/cc.24675. Epub 2013 Apr 17.

PMID: 23598722 [PubMed - in process]

Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C.
Sci Rep. 2011;1:95. doi: 10.1038/srep00095. Epub 2011 Sep 19.

PMID: 22355613 [PubMed - indexed for MEDLINE] Free PMC Article

Natoni A, Murillo LS, Kliszczak AE, Catherwood MA, Montagnoli A, Samali A, O'Dwyer M, Santocanale C.
Mol Cancer Ther. 2011 Sep;10(9):1624-34. doi: 10.1158/1535-7163.MCT-10-1119. Epub 2011 Jul 18.
PMID: 21768328 [PubMed - indexed for MEDLINE] Free Article

 

Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C.
Nat Chem Biol. 2008 Jun;4(6):357-65. doi: 10.1038/nchembio.90. Epub 2008 May 11.
PMID: 18469809 [PubMed - indexed for MEDLINE]

 

Tenca P, Brotherton D, Montagnoli A, Rainoldi S, Albanese C, Santocanale C.
J Biol Chem. 2007 Jan 5;282(1):208-15. Epub 2006 Oct 24.
PMID: 17062569 [PubMed - indexed for MEDLINE] Free Article
 
Montagnoli A, Valsasina B, Brotherton D, Troiani S, Rainoldi S, Tenca P, Molinari A, Santocanale C.
J Biol Chem. 2006 Apr 14;281(15):10281-90. Epub 2006 Jan 30.
PMID: 16446360 [PubMed - indexed for MEDLINE]
 
Montagnoli A, Tenca P, Sola F, Carpani D, Brotherton D, Albanese C, Santocanale C.
Cancer Res. 2004 Oct 1;64(19):7110-6.

PMID: 15466207 [PubMed - indexed for MEDLINE] Free Article

Montagnoli A, Bosotti R, Villa F, Rialland M, Brotherton D, Mercurio C, Berthelsen J, Santocanale C.
EMBO J. 2002 Jun 17;21(12):3171-81.
PMID: 12065429 [PubMed - indexed for MEDLINE] Free PMC Article

 

Santocanale C, Sharma K, Diffley JF.
Genes Dev. 1999 Sep 15;13(18):2360-4.
PMID: 10500092 [PubMed - indexed for MEDLINE] Free PMC Article
  
Santocanale C, Diffley JF.
Nature. 1998 Oct 8;395(6702):615-8.
PMID: 9783589 [PubMed - indexed for MEDLINE]


 
 
To view a complete list of publications, click here
Group Members
April 2013: Michael Rainey paper featured in the cover of Cell Cycle with a beautiful picture taken by Laura Murillo
 
 
March 2012: Michael Rainey win an award in the best proffered papers category at the Annual Meeting of the Irish Association for Cancer Research in Belfast.

 
 
 

January 2012: Ania pass her VIVA
We are proud of you !


Summer 2011: ALAN is awarded an HRB fellowship to perform a short project in our group...

...and in September he gets a GOLD medal for the best research project talk in the School of Medicine !

 

 

 
 
 

LAB Dinner Party August 2010
 
 

 
From the left:
 
Michael O'Dwyer
Alessandro Natoni
Michael Rainey
Laura Barkley
Corrado Santocanale
Laura Murillo
Anna Kliszczak
Mark Coyne
Gemma O'Brien
Carina Shortall
Jennifer Fitzgerald
Maria Dulak
Yvonne Crowley
 

 
   

 

 

 

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