Versatile genetic perturbation approach to understand tumor-immune interactions in human glioblastoma – UROP Spring Symposium 2024

Versatile genetic perturbation approach to understand tumor-immune interactions in human glioblastoma

Sajed Nehme

Pronouns: He/him

Research Mentor(s): Toshiro Hara
Research Mentor School/College/Department: Neurosurgery / Medicine
Program:
Authors: Sajed Nehme, Hamza Alnaib, Toshiro Hara
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 60

Abstract

The mechanism underlying how macrophages induce a transition of glioblastoma (GBM) cells into a mesenchymal (MES)-like state is unclear. Macrophages produce a cytokine known as Oncostatin M (OSM) proven to cause a transition of GBM cells into an MES-like state. Although the involvement of OSM in this process is recognized, the precise mechanism and potential additional factors remain uncertain. In this study, we employ the Neon electroporation system and CRISPR/CAS9 to deplete the OSM gene in the U937 monocytic cell line. We then induce differentiation of these monocytes into macrophages using Phorbol 12-myristate 13-acetate (PMA). To test whether or not and to what extent OSM mediates the transition of tumor cells into an MES-like state, the differentiation macrophages are co-cultivated with GBM cells. Our preliminary results suggest high transfection efficiency in U937 cells; yet, single-cell cloning by limiting dilution will be further required to generate clones lacking OSM. Given the central roles of the MES-like program in GBM, this research endeavors to contribute valuable insights into the relatively unknown microenvironment of GBM cells, with the ultimate goal of helping to create targeted therapeutic interventions to combat this disease.

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