Xuan Pan

Position title: Assistant Professor, Dept. of Medical Sciences

Email: xuan.pan@wisc.edu

Phone: (608) 265-4718

Address:
4470 Veterinary Medicine Building
2015 Linden Dr
Madison, WI 53706

Xuan Pan

RESEARCH:  It is of critical importance that the rates of hematopoietic stem cell (HSC) differentiation and self-renewal are carefully regulated and kept in balance, because severe disease states arise when this balance is disrupted. Unfortunately, the mechanisms that maintain this balance are poorly understood, and this lack of understanding represents a major roadblock to research progress, while also severely restricting the clinical potential of HSC-based therapeutic interventions. Our group identified PcG protein YY1 as an essential regulator of HSC self-renewal and differentiation in mice. Hematopoietic Stem Cell (HSC) quiescence is regulated by both intrinsic and extrinsic signals. Cell-cycle regulators, transcription factors, as well as epigenetic modifications, have been identified as intrinsic regulators of HSC cell-cycle progression. However, correlations of epigenetic signatures are often not highly instructive, and the mechanistic implication of epigenetic signatures in HSC self-renewal is incompletely understood. We have generated a conditional mouse knockout of YY1 in HSCs and showed that YY1 knockout decreases HSC long-term repopulating activity and ectopic YY1 expression expands HSCs. YY1-deficiency deregulates the genetic network that regulates HSC proliferation and impaired stem cell factor/c-Kit signaling, and interferes with establishment of quiescence in HSCs. These results reveal how a ubiquitously-expressed epigenetic repressor regulates lineage-specific functions and plays a critical role during hematopoiesis in adult mice.  Our group currently is focusing on assessing the structure-function relationships in YY1 and dissecting the underlying mechanisms that control chromosome structural change at the Kit locus.