Agnel Sfeir, Ph.D.

Research

The Sfeir lab explores the role that telomeres play in the biology of mammalian cells. In mammals, including humans, chromosomes are capped by protective structures called telomeres. Without these structures, cells may mistake the ends of normal chromosomes for “broken” DNA and attempt to repair them—a process that actually causes damage and can lead to cancer. But not all cells have telomeres. Some bacteria form a protective “loop” at the tips of their chromosomes; others get around the problem by having chromosomes that are circular. The lab’s aim is to remove the telomeres from mammalian chromosomes and either cap them with bacterial loops or circularize them. Sfeir’s team will then introduce these altered chromosomes into cells and observe how they are handled and whether the cells can tolerate these telomere alternatives. Because telomere dysfunction is associated with cancer and aging, this work will provide a new understanding of how cancer occurs and new anti-cancer therapies.

As an Innovation Fund investigator, Sfeir’s lab is collaborating with the lab of Ruth Lehmann, Ph.D., to combine an expertise in DNA inheritance with specialized knowledge in DNA replication and repair. Mitochondria, organelles within the cell, have their own genomes of DNA that are passed down from mother to child. Mutations in mitochondrial DNA can be severely detrimental, so cells limit the transmission of this mutant DNA. How this occurs, however, is not well understood. The pair will develop tools to probe how aberrant DNA is eliminated when mitochondria are passed on from a mother to her offspring, and also methods to specifically edit the mitochondrial genome. This work could help inform the development of therapies for mitochondrial-based diseases such as neurological disorders and age-related syndromes.