Current Research and Scholarly Interests
Aging is the primary risk factor for many human pathologies, including cardiovascular and neurodegenerative diseases, cancer, and diabetes. Yet, understanding how organisms age remains one of the biggest challenges in biology. Due to their short lifespan, non-vertebrate model systems (yeast, worms, and flies) have been widely used in experimental aging research. These studies revealed that the aging rate can be manipulated by genetic and environmental interventions, thus, underscoring that aging is not merely due to wear and tear. Rather, it is a complex trait that can be regulated by conserved mechanisms. However, the lack of short-lived vertebrate models for genetic studies has significantly limited our understanding of vertebrate aging, including the role of vertebrate-specific genes (e.g. IL8 and APOE), organs (e.g. bones and blood), and physiological processes (e.g. adaptive immunity).
We used the shortest-lived vertebrate model, the African turquoise killifish, to develop the first genetic platform for rapid exploration of vertebrate aging. This platform included a sequenced genome, CRISPR/Cas9-based genome editing, and mutant fish for many aging- and disease-relates genes. We focused on mutants for the protein subunit of telomerase, which displayed the fastest onset of telomere-related pathologies among vertebrate models. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high-throughput manner and for investigating candidates arising from human genome-wide studies.