Positions
- Assistant Professor
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Baylor College of Medicine
Addresses
- Huffington Center on Aging (Office)
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Baylor College of Medicine
One Baylor Plaza M320
Houston, TX 77030
United States
Education
- M.D. from Free University
- 01/1998 - Berlin, Germany
- Ph.D. from Free University
- 01/2002 - Berlin, Germany
- Post-Doctoral Fellowship at Dana-Farber Cancer Institute
- 01/2011 - Boston, Massachusetts United States
Professional Interests
- Role of microbiome in telomere shortening-induced colitis and colorectal cancer
Professional Statement
Telomeres, protective ends of linear chromosomes, and telomerase, the enzyme that maintains telomeres, are implicated in cancer and aging. Due to insufficient telomerase activity, telomeres in human cells shorten during aging and cause cells to undergo senescence. However, if sufficient telomerase activity is provided, cells become immortal and grow indefinitely. The discovery of this potent immortalization gene, telomerase, opens up the possibility that one can prevent and delay aging, not only on a cellular level, but potentially also in humans. Two of the fundamental questions in telomere biology is how short telomeres induce aging and conversely, how telomerase and the maintenance of long telomeres confer immortalization. My lab is interested in studying these two fundamental aspects.We have recently described a novel mechanism by which short telomeres impair the function of mitochondria. This multi-level analysis uncovered that short telomeres impinge on the ability organs to generate energy (ATP) by compromising mitochondria and other energy generating processes. Based on these initial findings, it will be essential to: (1) characterize what biochemical pathways are affected in detail and how that affects the total metabolic profile of tissues with short telomeres, (2) turn on telomerase and test whether and which metabolic and mitochondrial changes are reversible, and (3) identify the transcriptional regulators that are activated by telomerase and that reverse the metabolic and mitochondrial compromise. The identification of these telomerase-dependent regulators will allow us to specifically target these molecules to rejuvenate tissues while avoiding oncogenic transformation.
A second line research focuses on the epigenetic and transcriptional control of telomerase. Telomerase reactivation is a hallmark of over 85% of cancers and is required for tumorigenesis. The molecular events leading to the reactivation of telomerase are not well understood. A significant obstacle in studying the epigenetic and transcriptional mechanisms responsible for telomerase reactivation is the relative lack of model systems. My lab will take new approaches using mouse models and human cells to study the transcriptional de-repression of telomerase. The use of such model systems will pave the way for a better molecular understanding of one of the most fundamental aspects of tumor biology and allow the development of knowledge based therapeutics.
Websites
Selected Publications
- Muller FL, Colla S, Aquilanti E, Manzo VE, Genovese G, Lee J, Eisenson D, Narurkar R, Deng P, Nezi L, Lee MA, Hu B, Hu J, Sahin E, Ong D, Fletcher-Sananikone E, Ho D, Kwong L, Brennan C, Wang YA, Chin L, DePinho RA "Passenger deletions generate therapeutic vulnerabilities in cancer.." Nature. 2012 Aug 16;488(7411):337-42. Pubmed PMID: 22895339
- Sahin E, Depinho RA "Axis of ageing: telomeres, p53 and mitochondria.." Nat. Rev. Mol. Cell Biol.. 2012 Jun;13(6):397-404. Pubmed PMID: 22588366
- Hu J, Hwang SS, Liesa M, Gan B, Sahin E, Jaskelioff M, Ding Z, Ying H, Boutin AT, Zhang H, Johnson S, Ivanova E, Kost-Alimova M, Protopopov A, Wang YA, Shirihai OS, Chin L, Depinho RA "Antitelomerase Therapy Provokes ALT and Mitochondrial Adaptive Mechanisms in Cancer.." Cell. 2012 Feb 17;148(4):651-63. Pubmed PMID: 22341440
- Liesa M, Luptak I, Qin F, Hyde BB, Sahin E, Siwik DA, Zhu Z, Pimentel DR, Xu XJ, Ruderman NB, Huffman KD, Doctrow SR, Richey L, Colucci WS, Shirihai OS "Mitochondrial transporter ATP binding cassette mitochondrial erythroid is a novel gene required for cardiac recovery after ischemia/reperfusion.." Circulation. 2011 Aug 16;124(7):806-13. Pubmed PMID: 21788586
- Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell'antonio G, Mautner J, Tonon G, Haigis M, Shirihai OS, Doglioni C, Bardeesy N, Kimmelman AC "Pancreatic cancers require autophagy for tumor growth.." Genes Dev.. 2011 Apr 1;25(7):717-29. Pubmed PMID: 21406549
- Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner JW, Maratos-Flier E, Depinho RA "Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.." Nature. 2011 Jan 6;469(7328):102-6. Pubmed PMID: 21113150
- Zheng H, Ying H, Wiedemeyer R, Yan H, Quayle SN, Ivanova EV, Paik JH, Zhang H, Xiao Y, Perry SR, Hu J, Vinjamoori A, Gan B, Sahin E, Chheda MG, Brennan C, Wang YA, Hahn WC, Chin L, DePinho RA "PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.." Cancer Cell. 2010 May 18;17(5):497-509. Pubmed PMID: 20478531
- Kimmelman AC, Hezel AF, Aguirre AJ, Zheng H, Paik JH, Ying H, Chu GC, Zhang JX, Sahin E, Yeo G, Ponugoti A, Nabioullin R, Deroo S, Yang S, Wang X, McGrath JP, Protopopova M, Ivanova E, Zhang J, Feng B, Tsao MS, Redston M, Protopopov A, Xiao Y, Futreal PA, "Genomic alterations link Rho family of GTPases to the highly invasive phenotype of pancreas cancer.." Proc. Natl. Acad. Sci. U.S.A.. 2008 Dec 9;105(49):19372-7. Pubmed PMID: 19050074
- Gurumurthy S, Hezel AF, Sahin E, Berger JH, Bosenberg MW, Bardeesy N "LKB1 deficiency sensitizes mice to carcinogen-induced tumorigenesis.." Cancer Res.. 2008 Jan 1;68(1):55-63. Pubmed PMID: 18172296
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