Research

Adult somatic stem cells (SCs) must be regulated to ensure regenerative capacity. During aging, SC function becomes misregulated, leading to regenerative decline during age-associated pathologies. Therapies targeting SCs have been explored as treatments, but emerging interventions are limited by incomplete understanding of the pathways regulating SC behavior. Our lab is focused on elucidating two such processes: cell fate determination and SC migration.

Regulation of cell fate determination during regeneration and aging

• In the Drosophila intestine, we have previously identified that JNK-mediated spindle reorientation of dividing SCs drove cell fate determination. Spindle orientation becomes misregulated in the aging fly, contributing to dysplasia. We now aim to explore the role of spindle orientation in cell fate determination in the mouse airway, identifying signaling pathways regulating spindle orientation and determining the effects of aging on cell fate regulation.
  
  
• The effects on cell fate by cytoskeleton repositioning within the mitotic spindle have profound consequences on tissue and animal physiology. We aim to understand the mechanism in which cell signaling, such as Wnt and JNK, reorients the mitotic spindle in dividing SCs, and how spindle reorientation can affect cell fate outcomes of daughter cells.

Regulation of stem cell migration during regeneration and aging

• We have previously identified a critical role of Wnt-mediated SC migration during regeneration of the Drosophila intestine. We are now expanding this study to the mouse trachea, exploring the role and regulation of SC migration during mammalian airway repair.
  
  
• Misregulation of SC migration contributes to loss of tissue homeostasis. We are characterizing the effects of aging on SC migration in both fly and mouse barrier epithelia. We are identifying how signaling pathways becomes misregulated to disrupt SC migration, how these defects contribute to regenerative decline, and whether restoring SC migration can increase longevity.
  
  
• How do SCs ensure that division only occurs after migration is complete? Premature mitosis before SCs reach sites of injury results in the ectopic generation of cells. We are interested in understanding the coordination between cell cycle progression and migration and testing whether SC migration is dependent on cell cycle phase.