Janice (Hoi-Yee) Wong: Engineering cells to target the senescence-associated secretory phenotype

February 7, 2018 @ 9:00 am – 9:30 am
Rosebrugh Building
Rosebrugh Bldg, Toronto, ON M5S 3G9

Room: RS 211


Implicated in aging and age-related pathologies, the accumulation of senescent cells can prevent tissue repair and regeneration leading to loss of physiological function. Studies in model organisms have shown that the clearance of senescent cells leads to an increase in healthy lifespan and rejuvenation. Senescent cells exert a larger degenerative effect on neighbouring cells by acquiring senescence-associated secretory phenotypes (SASP) that releases inflammatory cytokines, growth factors and proteases. The seeking of interleukin-6 (IL-6), the most prominent SASP, could enable localization of engineered cells to senescent cells for therapeutic intervention. Engineered cells with no natural propensity to migrate to IL-6 can do so with the co-expression of a chimeric IL-6 receptor (IL-6Rchi) and Ca2+-actived RhoA (CarQ). Next, the removal of target cells can be achieved with a membrane fusion and death mechanism achievable by vesicular stomatitis virus G glycoprotein (VSVG). This work can offer as a starting point for further research into targeting senescent cells with increased specificity such as seeking multiple SASPs (such as TNFa, MMP3, PAI1, IL-8) simultaneously; and investigation of therapeutic potential in vivo.