Periodic Reporting for period 1 - KILNEV (Killing Senescent Cells as a Novel Method to Eliminate Nevi)
Okres sprawozdawczy: 2018-04-01 do 2020-03-31
The objectives are:
1) Elucidate and validate new genes of interest which modulate survival in senescent melanocytes.
2) Investigate whether siRNA mediated knockdown of these genes induce death of nevus cells in mice.
We next validated whether these proteins do modulate survival by silencing their expression using genetic knockdown experiments, or by inhibiting their function using pharmacological drugs. We indeed find that knockdown of these proteins do cause death in senescent, but not proliferating, melanocytes. We also used two pharmacological compounds called ABT-263 (an inhibitor of Bcl-w) and S63845 (an inhibitor of Mcl-1). These two drugs act together to also specifically kill senescent melanocytes.
We then aimed to investigate whether these two drugs could be topically administered onto mice nevi, in order to kill the nevus cells. Experiments carried out so far show reduced number of pigmented nevi in treated mice.