Our lab focuses on understanding what controls telomere length from a molecular level, with the hope that this knowledge will help us develop new therapies to treat telomere related diseases. This project began with the simple idea: What if there are pathways in the cell which regulate telomere length that we don’t even know about? To answer this question, Will Mannherz, an MD-PhD student in the lab, systematically tested all the genes in the genome (nearly 20,000) to see whether they are associated with telomere length. He did this by combining CRISPR based gene editing technology with the flow-FISH telomere length measurement test which is used clinically to diagnose telomere diseases.

When the results came back, we were surprised to see several genes which regulate thymidine nucleotide metabolism as top hits. Thymidine nucleotides are one of the four building blocks of DNA, including telomeres. We found that supplementing cells with thymidine could increase telomere length, including in cells derived from patients with telomere biology disorders. While working on this project, we were excited to learn that thymidine is already being using in clinical trials for another rare genetic disease, TK2 deficient myopathy. We are very interested in the prospect of translating thymidine to a clinical trial for telomere biology disorders, and are working on the initial phases of this process.

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