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Cell Ageing

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Oliver DREESEN

After completing his undergraduate degree in Bern, Switzerland, Oliver worked as a research technician at the Pasteur Institute in Paris, the University of California, San Diego and Lonza AG in Visp, Switzerland. As a graduate student, Oliver moved to the laboratory of Professor George A. M. Cross at the Rockefeller University in New York, where he studied the structure and function of telomeres and telomerase in Trypanosoma brucei. T. brucei is a protozoan parasite and the causative agent of African sleeping sickness. His Ph.D. research revealed that growth and breakage of telomeric repeats play an important role in regulating host immune evasion (antigenic variation) in trypanosomes.

As a postdoc, Oliver joined Professor Alan Colman’s laboratory at the Institute of Medical Biology in Singapore to study telomeres during cellular reprogramming and in rare genetic human diseases. Oliver was promoted to Project Leader in 2013; and to Principal Investigator in 2016. The focus of his laboratory is to investigate the role of telomere dysfunction and cellular senescence in the premature ageing syndrome Hutchinson-Gilford Progeria and during normal human ageing.

Age is the major risk factor for the development of chronic medical conditions. To enhance the well-being of the growing ageing population, it is crucial that we understand the biological processes of ageing and age-related diseases.

Our goal is to identify the molecular changes that occur in cells as they age. In particular, we focus on the role of telomeres and cellular senescence during the ageing process and in human disease. Telomeres cap the physical ends of chromosomes and ensure genome integrity by protecting chromosome ends from illegitimate activation of DNA damage checkpoints. Due to the "end replication problem", telomeres shorten with each replicative cycle. Critically shortened telomeres trigger senescence and can limit the regenerative potential of a tissue. Senescent cells accumulate with age in many tissues, particularly at sites of pre-neoplastic lesions or age-related pathologies and may serve as prognostic markers of disease onset and progression. However, many senescence-associated biomarkers are non-specific and hard to detect in vivo.

We are using cells from patients with accelerated ageing syndromes to identify novel ageing-associated biomarkers. The identification of such markers facilitates the development of tools to determine the biological, rather than the chronological age of human skin. Lastly, assessing the contribution of senescence to skin ageing and various skin-related pathologies forms the basis to identify strategies to prevent senescence.


Lamin B1 staining in normal human skin of young (1 yr; left) versus aged (>60 yr; right) individuals. Scale bar: 50 um.

 

Group Members

Senior Research Fellow Aya Wada
Research Fellow Audrey Wang
Senior Research Officer Ong Peh Fern
 Research Officer Louis-Peter Hor
 Intern Ryan Sim

Ling L, Camilleri ET, Helledie T, Samsonraj RM, Titmarsh DM, Chua RJ, Dreesen O, Dombrowski C, Rider DA, Galindo M, Lee I, Hong W, Hui JH, Nurcombe V, van Wijnen AJ, Cool SM. Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells. Gene. 2016 Jan 15;576(1 Pt 2):292-303. doi: 10.1016/j.gene.2015.10.039. Link
Chojnowski A, Ong PF, Wong ESM, Lim JSY, Mutalif RA, Navasankari R, Dutta B, Yang H, Liow YY, Sze SK, Boudier T, Wright GD, Colman A, Burke B, Stewart CL, Dreesen O. Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria. eLife. 2015 Aug 27; 10.7554/eLife.07759 Link
Chojnowski A, Ong PF, Dreesen O. Nuclear lamina remodelling and its implications for human disease. Cell Tissue Res. 2014 Dec 24. [Epub ahead of print] PubMed PMID: 25532872. Link
Dreesen O. “Skin Ageing: Mechanisms and ways to measure it.” Medical Grapevine, 10 Jun 2014, Online
Dreesen O, Ong PF, Chojnowski A, Colman A. The contrasting roles of lamin B1 in cellular aging and human disease. Nucleus. 2013 Jul-Aug;4(4):283-90. doi: 10.4161/nucl.25808. Epub 2013 Jul 18. PubMed PMID: 23873483; PubMed Central PMCID: PMC3810336. Link
Dreesen O, Chojnowski A, Ong PF, Zhao TY, Common JE, Lunny D, Lane EB, Lee SJ, Vardy LA, Stewart CL, Colman A. Lamin B1 fluctuations have differential effects on cellular proliferation and senescence. J Cell Biol. 2013 Mar 4;200(5):605-17. doi: 10.1083/jcb.201206121. Epub 2013 Feb 25. PubMed PMID: 23439683; PubMed Central PMCID: PMC3587829. Link
Hovel-Miner GA, Boothroyd CE, Mugnier M, Dreesen O, Cross GA, Papavasiliou FN. Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei. PLoS Pathog. 2012;8(8):e1002900. doi: 10.1371/journal.ppat.1002900. Epub 2012 Aug 30. PubMed PMID: 22952449; PubMed Central PMCID: PMC3431348. Link
Pomp O, Dreesen O, Leong DF, Meller-Pomp O, Tan TT, Zhou F, Colman A. Unexpected X chromosome skewing during culture and reprogramming of human somatic cells can be alleviated by exogenous telomerase. Cell Stem Cell. 2011 Aug 5;9(2):156-65. doi: 10.1016/j.stem.2011.06.004. PubMed PMID: 21816366. Link
Pomp O, Dreesen O, Colman A. The "X factor" in cellular reprogramming and proliferation. Cell Cycle. 2011 Dec 1;10(23):3992-3. doi: 10.4161/cc.10.23.18253. Epub 2011 Dec 1. PubMed PMID: 22101271. Link
Dreesen O, Stewart CL. Accelerated aging syndromes, are they relevant to normal human aging? Aging (Albany NY). 2011 Sep;3(9):889-95. PubMed PMID: 21931180; PubMed Central PMCID: PMC3227453. Link
Dreesen O* and Colman A* (2011). Induced Pluripotent Stem Cells. Stem Cells: From Bench to Bedside. Second Edition. World Scientific *co-corresponding author
Boothroyd CE, Dreesen O, Leonova T, Ly KI, Figueiredo LM, Cross GA, Papavasiliou FN. A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei. Nature. 2009 May 14;459(7244):278-81. doi: 10.1038/nature07982. Epub 2009 Apr 15. PubMed PMID: 19369939; PubMed Central PMCID: PMC2688456. Link
Colman A, Dreesen O. Pluripotent stem cells and disease modeling. Cell Stem Cell. 2009 Sep 4;5(3):244-7. doi: 10.1016/j.stem.2009.08.010. PubMed PMID: 19733533. Link
Colman A, Dreesen O. Induced pluripotent stem cells and the stability of the differentiated state. EMBO Rep. 2009 Jul;10(7):714-21. doi: 10.1038/embor.2009.142. Epub 2009 Jun 19. Review. PubMed PMID: 19543232; PubMed Central PMCID: PMC2727431. Link
Dreesen O, Cross GA. Telomere length in Trypanosoma brucei. Exp Parasitol. 2008 Jan;118(1):103-10. Epub 2007 Aug 29. PubMed PMID: 17910953; PubMed Central PMCID: PMC2233935. Link
Dreesen O, Brivanlou AH. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. 2007 Jan;3(1):7-17. Review. PubMed PMID: 17873377. Link
Dreesen O, Li B, Cross GA. Telomere structure and function in trypanosomes: a proposal. Nat Rev Microbiol. 2007 Jan;5(1):70-5. Epub 2006 Dec 11. PubMed PMID: 17160000. Link
Dreesen O, Cross GA. Consequences of telomere shortening at an active VSG expression site in telomerase-deficient Trypanosoma brucei. Eukaryot Cell. 2006 Dec;5(12):2114-9. Epub 2006 Oct 27. PubMed PMID: 17071826; PubMed Central PMCID: PMC1694812. Link
Dreesen O and Cross GAM (2006). Telomerase-independent stabilization of short telomeres in T. brucei. Molecular and Cellular Biology
Dreesen O, Li B and Cross GAM (2005). Telomere structure and shortening in telomerase-deficient Trypanosoma brucei. Nucleic Acids Research
Janzen CJ*, Lander F*, Dreesen O and Cross GAM (2004). Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei. Nucleic Acids Research *equal contribution
Kobayashi K, Ehrlich SD et al., (2003). Essential Bacillus subtilis genes. Proc. Natl. Acad. Sci. USA
Cruz Ramos H, Hoffmann T, Marino M, Nedjari H, Presecan–Siedel E, Dreesen O, Glaser P, Jahn D (2000). Fermentative metabolism of Bacillus subtilis: Physiology and regulation of gene expression. Journal of Bacteriology
King N, Dreesen O, Stragier P, Pogliano K, Losick R (1999). Septation, dephosphorylation and activation of sigmaF during sporulation in Bacillus subtilis. Genes and Development