Zachary Yochum


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Zachary Yochum

Student Year: 
G 3
Graduate Program: 
Molecular Pharmacology
Alan Wells, MD
Undergraduate Institution: 
University of Notre Dame

Mutant KRAS is an important oncogenic driver in non-small cell lung carcinoma (NSCLC). Although, 25% of all NSCLCs have KRAS driver mutations, no effective targeted therapies exist for KRAS driven tumors. TWIST1, an embryonic transcription factor, is commonly overexpressed in NSCLC and is associated with a more aggressive tumor phenotype and worse prognosis. Our lab has demonstrated that TWIST1 inhibition in KRAS mutant NSCLC cells can induce oncogene induced senescence or apoptosis. Interestingly, we have preliminary data to suggest that high TWIST1 expression may correlate with an apoptotic phenotype. The fact that certain KRAS mutant cell lines undergo apoptosis following TWIST1 KD suggests that these cells are potentially “addicted” to the TWIST1 oncogene and might be more vulnerable to TWIST1 targeted therapies. We hypothesize that TWIST1 is required to suppress apoptosis in a subset of KRAS mutant NSCLC cells with high TWIST1 expression. In the present study, we have set out to characterize the pathways required for apoptosis after TWIST1 inhibition.