The continued health of many of our organs, including the skeleton, relies on the function of specialized stem cells. These stem cells reside in NICHES that support their long-term maintenance. Disruption of the NICHE, due to aging, injury, or genetic mutations, can lead to declines in stem cells and a failure to maintain and repair tissues. Compared to our understanding of the stem cells that maintain and repair our skeleton, we know much less about the cell types that constitute their NICHE. My prior large-scale genomics studies have uncovered a novel NICHE cell type for the skeleton. Intriguingly, these NICHE cells are defined by a unique metabolic profile, in particular enzymes for Phenylalanine (Phe) / Tyrosine (Tyr) metabolism and glycogen synthesis. Mutations in Phe/Tyr metabolism genes lead to skeletal diseases in humans, HGD (Alkaptonuria, aka “black bone disease”) and PAH (Phenylketonuria), suggesting a critical role of metabolism in NICHE cells to support the stem cells that maintain the skeleton. I have generated the first animal model for Alkaptonuria; hgd mutant zebrafish that fully recapitulate the black bone phenotype of human patients. I will establish a research group that leverages the powerful genomic, genetic, and high-resolution imaging strengths of zebrafish to test the roles of metabolism in stem cell maintenance. Findings from my proposed studies will inform future therapies aimed at correcting metabolic diseases and restoring stem cell function and skeletal health by modulating the NICHE.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.