Nick Baker

The mammalian liver possesses a remarkable ability to regenerate following injury. Contrary to the model of stem-cell-mediated regeneration, most new hepatocytes in regenerating livers arise through self-duplication. But, the underlying mechanisms that drive quiescent hepatocytes to divide after injury remain poorly defined. Recently, our laboratory discovered that in response to injury, a subset of hepatocytes transiently reactivates fetal-like gene expression programs to proliferate, while a distinct population of metabolically hyperactive cells compensates for any temporary deficits in liver function. As a CBI trainee, my thesis project will be to investigate genetic mechanisms, especially RNA processing activities, and cell-cell signaling interactions, that coordinate the initiation and termination phases of liver regeneration. Additionally, I will be integrating single-cell genomics datasets with spatial transcriptomics to identify the important RNA and protein targets that support hepatocyte proliferation while maintaining essential metabolic functions. Elucidating the molecular basis of liver regeneration will help identify key targets that can be developed as ‘regenerative therapeutics’ to stimulate healthy tissue repair in individuals with chronic liver diseases.