Lisa Petti

My research in the DiMaio lab is focused on understanding the action of certain cell surface proteins known as receptors. Some receptors play an important role in the abnormal behavior of cancer cells, while others serve as attachment sites for viruses. We have developed a novel method to engineer very small proteins that can modulate the activity of these receptors. So far, we have isolated several of these small proteins that can inhibit the activity of specific receptors. These small proteins should be useful tools for understanding how we can control the activity of cell surface receptors to inhibit cancer cell growth and abate viral infection.

Specialized Terms: receptor tyrosine kinase signaling; cellular growth transformation; virology; transmembrane protein-protein interactions

I am interested in investigating growth factor receptor tyrosine kinases and their role in oncogenesis. My research has involved utilizing a viral oncoprotein, the bovine papillomavirus (BPV) E5 protein, to explore activation and signaling mechanisms of the beta receptor for platelet-derived growth factor (PDGFR), which is involved in a several human cancers. My postdoctoral work showed that E5, a small transmembrane protein, binds to the PDGFR via transmembrane domain interactions and activates this receptor to promote cellular growth transformation. I then became interested in investigating the effects of E5 in mortal human fibroblasts (HDFs) in an effort to determine how the PDGFR is implicated in cancer. My lab at Albany Medical College showed that sustained activation of the PDGFR has both oncogenic and apoptotic effects in these cells. We identified a novel PDGFR signaling pathway involving SHP-2 that plays a role in transformation of HDFs. In addition, we showed that sustained PDGFR signaling in HDFs results in the production of an apoptotic peptide, which acts in an autocrine/paracrine manner to induce mitochondrial dysfunction. Currently, I am working on a project in the DiMaio lab investigating artificial small transmembrane proteins, termed "traptamers", modeled after the E5 protein. So, far we have identified several traptamers that can activate the PDGFR even thought they share little or no sequence similarity to E5. Recently, we showed that single conservative amino acid substitutions in such traptamers can convert them into inhibitors of the PDGFR. Future studies investigating the mechanism by which these mutated traptamers inhibit PDGFR signaling should provide new insight into PDGFR signaling as well as a basis for developing novel therapeutics.