db Home Program in Developmental Biology BCM Home
Baylor College of Medicine
Previous Faculty List Next

Ergun Sahin

Ergun Sahin

E-mail: esahin@bcm.edu

Assistant Professor, Baylor College of Medicine

M.D., Free University of Berlin, Germany, 1998
Ph.D., Free University of Berlin, Germany, 2001
Postdoc, Dana Farber Cancer Institute, Boston, MA, 2010


Telomere function, aging and cancer biology

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.


Selected Publications

Sahin E, Depinho RA (2010) Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 464:520-528.

Sahin E, Colla S, Liesa M, Moslehi J, Müller FL, Guo M, Cooper M, Kotton D, Fabian AJ, Walkey C, Maser RS, Tonon G, Foerster F, Xiong R, Wang YA, Shukla SA, Jaskelioff M, Martin ES, Heffernan TP, Protopopov A, Ivanova E, Mahoney JE, Kost-Alimova M, Perry SR, Bronson R, Liao R, Mulligan R, Shirihai OS, Chin L, DePinho RA (2011) Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 17:359-365.

Sahin E, DePinho RA (2012) Axis of ageig: telomeres, p53 and mitochondria. Nature Reviews Molecular Cell Biology 13:397-404.

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 (2012) Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer. Cell 148:651-663.


Contact Information

Ergun Sahin, M.D., Ph.D.
Huffington Center on Aging
Baylor College of Medicine
One Baylor Plaza, M320
Houston, Texas 77030, U.S.A.

Tel: (713) 798-6685
E-mail: esahin@bcm.edu

Previous Faculty List Next