Screening for Drugs to Cure the Pediatric Liver Cancer Fibrolamellar Hepatocellular Carcinoma

Background

Fibrolamellar hepatocellular is usually a lethal disease that occurs in children, adolescents and young adults. It was recently demonstrated that the vast majority of the genome in the tumor is clean of mutations with one exception: a deletion on one copy of one chromosome that fuses a heat shock protein with the enzymatic unit of protein kinase A. This has been shown in every patient out of almost 300 patients tested. This fusion protein is not found in the normal tissues or anywhere in the body. It is similar to the fusion of BCR with Abl (which is also a kinase) in some leukemias. A drop that blocks the BCR-Abl fusion has been a lifesaver. A drop that can block the fusion protein in fibrolamellar offers similar hope. 

Project Goal

The lab of my mentor has structural information on the fusion protein from X-ray crystallography, NMR and molecular simulations. They are looking for chemists to work with them on using this information to block the fusion protein. With the help of Schrodinger software on the simulations, and various chemists around the country, there is a good potential to find a blocker.

My undergraduate training was in chemistry and I plan to attend graduate school in chemistry next year.  I was diagnosed with fibrolamellar recently, which has left me with a strong desire to apply my chemical training to cancer biology.  This is the perfect project for me.