2020-2023 Recipient: Matteo Gianesello

Matteo Gianesello is the winner of the Pezcoller Foundation - Casse Rurali Trentine PhD fellowship 2020-23. He is working in the Armenise-Harvard Laboratory of Cancer Disoders and Cancer, led by Prof. Luca Tiberi.

To study the molecular mechanisms by which Notch1 induces Medulloblastoma (with human brain organoids)
 
Medulloblastoma (MB) is a devastating childhood cancer that it is currently divided into four molecular subgroups, of which Group 3 MB is the most aggressive subtype. We have recently developed the first human organoid-based Group 3 MB model (Ballabio et al., 2020a), and we found that S100b+ cells are competent to generate Group 3 MB whereas Math1+ progenitors are not susceptible to oncogene transformation (Ballabio et al., 2020b). A key difference between S100b+ cells and Math1+ cells is the status of the Notch pathway. 
Therefore, in the three years of Ph.D, we aim to identify the mechanisms by which Notch activity influences cerebellar progenitors competence for cancer transformation:
A) To validate whether Notch1, together with MYC+Gfi1, induces MB in human cerebellar organoids.
B) To study the molecular mechanisms by which Notch1 and MYC+Gfi1 induce MB in human cerebellar organoids