January 18, 2024
Bret Freudenthal, PhD, associate professor of biochemistry and molecular biology at the University of Kansas Medical Center, has received a prestigious Emerging Leader Award from The Mark Foundation for Cancer Research. The program supports innovative cancer research conducted by the next generation of leaders. Grants are awarded to outstanding early career investigators to support high-impact, high-risk projects that are distinct from their current research portfolio.
The $750,000 award will support Freudenthal's research into DNA damage and cancer development. Our genetic material is stored in structures called chromosomes, and at the ends of these chromosomes are repetitive DNA sequences known as telomeres. We rely on telomeres to protect our genetic information during cell division. However, as cells divide, the telomeres naturally shorten. An enzyme called telomerase can counteract this shortening by elongating telomeres. In about 85-90% of cancers, the activity of telomerase is increased to lengthen telomeres and counteract the shortening of the telomere, ultimately allowing the cancer to continue growing.
When telomerase extends a telomere, it does so by inserting deoxynucleotides (DNA), but they can also contain ribonucleotides (RNA). Ribonucleotides are a common form of DNA damage and are associated with some cancer types. The biological impact of ribonucleotides within telomeres, however, is unclear. To address this limitation, Dr. Freudenthal and his team developed a telomerase mutant that specifically inserts ribonucleotides and identified a cancer-associated telomerase mutation that enhances ribonucleotides insertion. This effort was originally supported by a pilot grant from KU Cancer Center.
With funding from The Mark Foundation for Cancer Research, Dr. Freudenthal will investigate the levels of ribonucleotides in telomeres, their impact on telomere integrity and viability and how they alter the DNA damage response. Additionally, they will explore how ribonucleotides within telomeres are identified, removed, and repaired.
“I am truly honored to receive this award from The Mark Foundation, which supports our efforts in better understanding the impact of ribonucleotides on telomere integrity,” Dr. Freudenthal said. “Our goal is to gain insights that will aid in developing strategies to protect telomere integrity, ultimately working towards the prevention of cancer development.”