The ASPIRE Path in Molecular Medicine

Precision oncology holds great promise for the treatment of cancers. Activating mutations in the ErbB receptor renders resistance to many FDA-proven inhibitors. However, there is a lack of data on resistance mutations. A high-throughput assay to characterize the mutational spectrum of the ErbB receptors is a powerful tool in predicting the emergence of drug resistance. I am developing a FACS-based assay that detects receptor activity through phosphorylation. This, coupled with site-saturated mutation libraries will be used to study the effect of mutations in different regions of the ErbB receptors on its activity in both homo and heterodimers. With my clinical mentor through APMM (Dr. Christine Lovly), I will extend this for screening TKIs and to characterize subtypes of EGFR variants (e.g. Exon-19 variants). I am also studying interactions between Ras-GTPase subfamily members and their activators and effectors. Identification of interacting interfaces will generate a plethora of information that can be translated to designing specific inhibitors. I expect these findings will have a significant impact on the realm of cancer biology. The APMM will equip me with a better understanding of the care of patients with cancers, molecular mechanisms of acquired drug resistance, and clinical and translational aspects of my research.