Alfred Freeberg

Cancers frequently hijack genetic programs to sustain growth, promote metastasis, and become treatment resistant. One crucial genetic program, Notch signaling, is often overactivated in cancers and promote tumor cell survival. My project targets a critical component of this pathway, the TLE family of corepressors, which help silence genes that would normally suppress tumor growth or trigger cell death. I propose to develop small-molecule inhibitors that disrupt TLE function and reactivate these protective genetic programs. Using high-throughput screening, structural biology, and functional genomics, I will identify and characterize compounds that inhibit TLE interaction with their binding partners. By restoring expression of protective gene programs, these molecules have the potential to reduce tumorigenesis, induce apoptosis, and impair metastasis in aggressive cancers, providing first-in-class therapeutics against TLE and Notch driven cancers.