- Huffington Center on Aging (Office)
- Baylor College of Medicine One Baylor Plaza M320 Houston, Texas 77030 United States
- Assistant Professor
- Baylor College of Medicine
- M.D. from Free University
- Ph.D. from Free University
- Post-Doctoral Fellowship at Dana-Farber Cancer Institute
- 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.
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