Earl Hwande

Coordination between cell proliferation and differentiation using C.elegans germline stem cells.

The nematode Caenorhabditis elegans(C. elegans) has a stereotypical cell lineage, offers powerful tools of genetic manipulation, a fully sequenced genome, and extensive conservation of genetic pathways between humans and C. elegans, which makes the nematode apowerful model organism for researchersto probe into the manner in which stem cells differentiate or proliferate. Understanding of the process in which stem cells undergo self-renewal, the regulatory circuitry that sustains their pluripotency, and eventsthatcommit progeny cells to particular differentiation states are key aspects of stem cell biology that are extremely critical. Stem cells are strongly associated with maintaining tissue repair, homeostasis, development, aging and cancer, while the soma has a fixed stereotypical lineage, the germline is the only tissuein the nematodethat remains proliferative throughout its life and hence supports a pool of proliferative germline stem cells. Maintaining a proper balance between proliferation and differentiation is critical to maintaining homeostasis; too much proliferation would result in tumors and premature differentiation would result in too few gametes. We are investigating the role of miRNAs, small regulatory non-coding RNAs, in maintaining stem cell homeostasis. Specifically, we want to investigate if over-expression of specific miRNAs is sufficient to drive tumor formation by inhibiting tumor suppressors