Basic Regeneration Research Using Model Organisms
We have a core interest in understanding the basis of the evolutionary divergence of regenerative capacity among species. Adult humans and other mammals do not have the ability to regenerate large portions of complex tissues after injury. In contrast, some lower vertebrates such as urodele amphibians (newts and salamanders) and zebrafish are endowed with extraordinary regenerative capacity. We are studying how evolutionary genetic changes account for these differences. We have approached this question by developing transgenic zebrafish models that are “humanized” with respect to their complement of tumor suppressor genes. We have found that the presence of the mammalian INK4a tumor suppressor locus which does not exist in fish, does not affect development but markedly compromises regenerative capacity, providing experimental evidence that the evolution of tumor suppression results in a trade-off at the expense of regenerative ability. We also have an ongoing interest in identification of novel evolutionary genetic differences and evaluation of their impact on regenerative capacity using cross-species genetic models.
Translational Regeneration and Stem Cell Biology
Our laboratory maintains a strong translational focus and a primary goal is to develop approaches for clinical applications of human skeletal muscle stem cells (satellite cells). Towards this end we have an active effort in preclinical studies of human satellite cell transplantation. The experiments leverage our clinical expertise and access to tissue with our scientific foundation in mouse skeletal muscle regeneration and stem cell biology. We have recently analyzed the frequency of satellite cells in diverse human muscles, and developed approaches to isolate and transplanted human satellite cells that fulfill criteria of bona-fide stem cells. We are using this robust xenograft model system to study human muscle stem cells in faithful preclinical models of limb and craniofacial muscle disorders. These preclinical studies will pave the way for development of clinical applications. We also have an active program investigating basic human and mouse muscle stem cell biology including transcriptomics, quiescence, heterogeneity and aging.