2019 New Investigator Grant

Sujatha Venkataraman, Recipient

University of Colorado Denver

MIC2 inhibition mediated apoptosis in DIPG

Abstract:

DIPG is a highly aggressive brain tumor of childhood that is largely fatal. Survival from diagnosis averages only 11 months. New research has identified genetic mutations in DIPG tumors but the genetic data have not yet resulted in new therapeutic options. Most patients have mutations in histone genes, namely H3K27M. How these mutations regulate DIPG tumor cell biology is not completely clear. To address this problem, we inserted the H3K27M mutation into non-mutant isogenic cells and examined the genomic changes driven by the mutation. Among the genes most upregulated by the H3K27M mutation was the MIC2 gene. The MIC2 gene codes for a cell surface protein, CD99 that can be targeted with therapeutic antibodies. Here we propose to comprehensively evaluate the action of CD99 in DIPG and establish preclinical data to support the rationale for targeting MIC2 for DIPG therapy.