Our lab is studying the relationship between form and function of the human genome. Nuclear organization and nuclear function are inextricably linked. For example, gene expression is related to nuclear localization, with silenced genes frequently positioned at heterochromatin and the nuclear periphery, and active genes enriched in the nuclear interior. Moreover, we have established a relationship between gene expression and genomic organization during cellular differentiation by contrasting the linear arrangement of co-regulated genes and the organization of all chromosomes in a hematopoietic progenitor and derived cell types.
We suggest that the inter-linked functions of the nucleus results in its self-organization, defined as the emergence of a global structure from combined local activities. Stem cells represent an ideal model to examine the functional role of nuclear self-organization, since their unique cellular properties are likely reflected in shared nuclear characteristics. My lab intends to both describe and probe the role of nuclear organization in stem cell maintenance and differentiation. We aim to characterize the mechanistic role transcription plays in organizing the nucleus during the renewal and commitment of stem cells and determine the ability of the nucleoskeleton to dynamically integrate cellular signals that yield these two fates. We suggest that these studies will be relevant to our understanding of the role stem cells play in aging and disease states such as cancer. Learn more