Our laboratory uses zebrafish to find genes that are crucial for the growth and survival of rapidly multiplying cells during the development of the zebrafish digestive system. We then test if these genes are also used by cancer cells to grow and survive.
We found a couple of genes that are essential for the growth of many cancers, including hard-to-treat ones like lung, liver, stomach, and bowel cancer. These types of cancer cause almost half of all cancer deaths worldwide, so we urgently need new treatments.
Our current focus is to discover drug-like compounds that can disable these genes in cancer cells without harming healthy ones. We have partnered with a European pharmaceutical company to speed up this process by screening hundreds of thousands of chemical compounds to find potential drugs. This approach has been successful in the past, and we hope it will lead to the development of effective cancer treatments.
Our mission: To tap into developmental processes to identify novel cancer targets.
Our vision: To use our skills to contribute to the discovery of new drugs that are effective against hard-to-treat cancers in a caring and rewarding workplace.
Assoc Prof Joan Heath’s lab is one of the first in the world to demonstrate the value of zebrafish as a model for discovering genes relevant to the behaviour of solid tumours. Working with zebrafish, mice and human cell cultures, her lab has made seminal contributions to our understanding of the genetic mechanisms that regulate the rapid growth of tissues during early development.
Using an ENU-mutagenesis screen in zebrafish, students and post-docs in her lab identified ten genes that are indispensable for the rapid proliferation of cells during organogenesis. The team then went on to show that two of these are also essential for vigorously proliferating cancers, in particular those driven by the powerful oncogene, mutant KRAS. These painstaking genetic studies over almost 20 years are now being translated into a clinically relevant project designed to identify small molecules that selectively inhibit the function of these genes for the purpose of cancer treatment.
Almost 20 years ago, a post-doc in the Heath lab spent 3 months at the University of California, San Francisco to participate in a focused genetic screen in zebrafish being carried out in the lab of Professor Didier Stainier. Her goal was to identify genes that are indispensable for the huge expansion of the digestive organs during vertebrate development. This work yielded a collection of ten zebrafish mutants with abnormalities in the size and shape of the liver, pancreas and intestine. Students and post docs in the Heath lab then identified the mutant genes underlying these abnormal digestive organ morphologies and uncovered a group of RNA processing genes, transcription factors and nuclear pore components that are essential for the rapid replication of cells during organogenesis.
More recently, the lab has used genetically engineered cancer models to show that several of these essential genes are also indispensable for the growth of tumours. Our current focus is to use high throughput chemical screening to identify inhibitors of these interesting genes, and the processes they are involved in, and determine whether they provide effective and viable targets for cancer therapy.