THESIS DEFENSE — PUBLIC SEMINAR: GENOME-WIDE SCREEN FOR REGULATORS OF TERT TRANSCRIPTION

Start Date & Time: 
Tuesday, 26 September, 2017 - 02:00
End Date & Time: 
Tuesday, 26 September, 2017 - 03:00
Venue: 

Meeting Room 7C, Level 7,  Duke-NUS

Speaker: 
Speaker Details: 

MUHAMMAD KHAIRUL RAMLEE
IBM PhD PROGRAM (INTAKE 2012)

Synopsis: 

Telomeres are nucleoprotein structures found at the ends of chromosomes. In somatic cells, telomeres shorten as these cells divide. When telomere reaches a critically short length, these cells undergo replicative senescence and eventually die. In contrast, stem and progenitor cells have the ability to maintain their telomere length via the expression of an enzymatic complex called telomerase. Similarly, more than 85% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase reverse transcriptase (TERT), the catalytic subunit of the telomerase holoenzyme, is considered to be the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of human TERT is known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors. However, the mechanism by which TERT expression is upregulated in cancer, downregulated in differentiating cells, and maintained in stem and progenitor cells is still unclear. In order to elucidate this elusive mechanism, we performed a genome-wide knock-out screen to look for regulators of TERT gene transcription using GFP as a molecular expression marker of TERT. From this screen, we discovered novel modulators of TERT expression including transcription factors and epigenetic modifiers. We are currently in the process of elucidating the mechanistic roles played by these regulators in the expression of telomerase and tumorigenesis in general. We intend to examine the viability of targeting these factors as a means of therapeutic treatment for patients suffering from telomerase dysfunction-mediated pathologies such as cancer and pre-mature aging.

Thesis Advisor: Dr. Shang Li