Investigate Alternative Lengthening of Telomeres (ALT) in Cancers with the SMTA
Wednesday, June 28, 2023
9:30 AM-11:30 AM
BIOMED PhD Research Proposal
Title:
Investigate Alternative Lengthening of Telomeres (ALT) in Cancers with the Single-molecule Telomere Assay (SMTA)
Speaker:
Heba Z. Abid, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Ming Xiao, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
Telomere is a repeated sequence (TTAGGG)N that caps the end of the chromosomes to protect them from damage during DNA replication prior to cell division. Telomere length is essential to the cell's genomic stability and biological function. Each division shortened the telomere by approximately 40 to 200bp. After multiple rounds of cell division, telomere shortening leads to genomic instability, which triggers DNA Damage Response (DDR), leading to senescence or apoptosis. In rare cases, 1 out of 10 million cells activates the telomere maintenance mechanisms (TMMs) to maintain cell immortality and lead to cancer. Approximately 85 to 90% of cancers maintain telomere length by activating telomerase expression, while the remaining 10-15% of cancers use Alternative Lengthening of Telomeres (ALT). Recent studies indicate that Homology-Dependent Repair (HDR) plays a role in the ALT pathway. Unlike Telomerase, HDR doesn't use a standard template; instead, HDR searches for a DNA template complement to the broken DNA strand. As a result, ALT telomeres are characterized by highly heterogeneous telomeres, including very long telomeres and telomere-free chromosome end, and unique telomere structures such as extrachromosomal telomeric DNA.
To further our knowledge in Alternative Lengthening of Telomeres in ALT cancers for better diagnostics and therapy, my proposal focuses on the following three aims: 1) Define the ALT positivity of cancers using the single-molecule telomere assay (SMTA) via Optical Mapping (SMTA-OM). 2) Determine DNA2 and FANCM affect the genome-wide telomeres in ALT+ cells. 3) Investigate the Role of POLD3 and PIF1 in The Telomere Repair Pathway in ALT Cancer cells.
ALT cancers include some of the deadliest and most difficult-to-treat cancers. Understanding telomere maintenance mechanisms in ALT cancer presents a potential for finding biomarkers for cancer diagnosis and helps explore targets for anticancer therapy
Contact Information
Natalia Broz
njb33@drexel.edu