UniTS
University of Trieste
SCHOOL OF MOLECULAR
BIOMEDICINE
PhD program in Molecular Biomedicine
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Dr. Stefan Schoeftner

L.N.CIB - AREA Science park
Padriciano 99 - 34149 Trieste

email: stefan.schoeftner@lncib.it

Phone +39 040 3756805
Fax +39 040 398990



Biosketch

Since 03.2013: Laboratorio Nazionale CIB, Trieste, Italy, AIRC-Start up Group
09.2010 – 02.2013: Istituto Nazionale Tumori, Regina Elena, Rome, Italy AIRC-Start up Group
09.2009 - 08.2010: Laboratorio Nazionale CIB, Trieste, Italy
Cancer Epigenetics Group (R. Benetti); Postdoctoral Fellow
03.2006 - 08.2010: Spanish National Cancer Centre (CNIO) Madrid, Spain
Telomere and Telomerase Group (M. Blasco); Postdoctoral Fellow
10.2001 - 12.2005: Research Institute of Molecular Pathology (IMP),Vienna, Austria
X-inactivation Group (A. Wutz); PhD student
05.1999 - 12.2000: Research Institute of Molecular Pathology (IMP), Vienna, Austria
B-cell development Group (M. Busslinger); Master student

PhD: University of Vienna, 2005

 

Research interests

Telomeres in Cancer and Ageing:

Telomeres are nucleoprotein structures that protect chromosome ends from DNA repair mechanisms.  Telomeres consist of TTAGGG repeats, are essential for the maintenance of genomic stability and consequently play a central role in cancer and organismal ageing. Telomere repeats get progressively shorter during life-time until they lose functionality and induce a DNA damage signal that causes cells to enter senescence or activate apoptosis – two processes that provide the basis for organismal ageing. Only stem cells can slow down the erosion of telomeres by expressing telomerase (TERT), a reverse transcriptase that can add back telomere repeats to chromosome ends. 
Immortalization of normal cells is paralleled by the re-activation of telomerase activity protecting cancer cells from telomere shortening. Consequently, TERT plays a central role in almost all tumors by ensuring the immortality of cancer cells.

Several telomere-associated proteins have been identified that are essential for a balanced telomere function. The protein complex “shelterin” is central for telomere protection and telomere length regulation. Further, the recently discovered non-coding telomere repeat containing non-coding RNA “TERRA”, act as natural inhibitor of telomerase activity and impact on telomeric chromatin structure. Altering the equilibrium of telomere regulators is expected to impact on telomere function and is therefore relevant for telomere-associated maladies such as cancer and ageing.

telomeres

Our Aims:
Our group is focused on the discovery of novel mechanisms controlling the equilibrium of telomere function and homeostasis.
We want to identify non-coding RNA pathways that alter the expression of central telomere regulators. The relevance of these pathways will be assessed in model systems for cancer and ageing model. A special focus will be given on elucidating the molecular mechanisms the lincRNA TERRA uses to control telomere function and chromatin regulation.

 

Selected publications

1. Schoeftner S, Scarola M, Comisso E, Schneider C, Benetti R. An Oct4-pRb axis, controlled by MiR-335, integrates stem cell self-renewal and cell cycle control. Stem Cells. 2012

2. Scarola M, Schoeftner S, Schneider C, Benetti R. miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer Research. 2010

3. Martinez P, Thanasoula M, Carlos AR, Gómez-López G, Tejera AM, Schoeftner S, Dominguez O, Pisano DG, Tarsounas M, Blasco MA. Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nature Cell Biology. 2010

4. Schoeftner S, Blanco R, Lopez de Silanes I, Muñoz P, Gómez-López G, Flores JM, Blasco MA. Telomere shortening relaxes X chromosome inactivation and forces global transcriptome alterations. Proc Natl Acad Sci U S A. 2009

5. Schoeftner S, Blasco MA. Chromatin regulation and non-coding RNAs at mammalian telomeres. Semin Cell Dev Biol. 2010

6. Schoeftner S, Blasco MA. A 'higher order' of telomere regulation: telomere heterochromatin and telomeric RNAs. EMBO J. 2009

7. Marion RM, Strati K, Li H, Tejera A, Schoeftner S, Ortega S, Serrano M, Blasco MA. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell. 2009

8. Muñoz P, Blanco R, de Carcer G, Schoeftner S, Benetti R, Flores JM, Malumbres M, Blasco MA. TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis. Mol Cell Biol. 2009

9. Benetti R, Schoeftner S, Muñoz P, Blasco MA. Role of TRF2 in the assembly of telomeric chromatin. Cell Cycle. 2008

10. Benetti R, Gonzalo S, Jaco I, Muñoz P, Gonzalez S, Schoeftner S, Murchison E, Andl T, Chen T, Klatt P, Li E, Serrano M, Millar S, Hannon G, Blasco MA. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008

11. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Schoeftner S, Blasco MA. Nat Cell Biol. 2008

 

 
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