Generation of Human Synthetic Antibodies to Investigate the Biological Functions of the Receptor Tyrosine Kinases HER3 and PTK7

Receptor tyrosine kinases or RTKs are an important class of signaling proteins that are frequently deregulated in cancer and other diseases. Based on a series of genetic screens to identify fitness genes across a compendium of cancer cell lines, the Moffat lab identified the receptor kinases HER3/ERBB3 and PTK7/CCK4 as important for the fitness of breast, pancreatic, ovarian, and colon cancer cell lines. Interestingly, both of the RTKs are predicted to have no kinase activity, suggesting that they are not likely amenable to direct enzymatic inhibition by small molecule chemical inhibitors. Using emergent synthetic antibody phage-display technology, I describe my efforts to generate and characterize synthetic antibodies targeting the extracellular regions of the receptor tyrosine kinases HER3 and PTK7.MAS