Autoimmune Disease and Cancer

Autoimmune Disease and Cancer

 

Collaborative Research Project: Tracking Down the ‘Rogue Clones’ at the Root of Autoimmune Disease and Cancer

Researchers at the Weizmann Institute and Garvan, led by Professor Chris Goodnow and Professor Ido Amit, are using cellular genomics to uncover ‘rogue clones’ of blood cells that give rise to many autoimmune diseases and blood cancers. They will identify vulnerabilities in these rogue clones to immunotherapy or other  drugs,  with  the  ultimate aim of eradicating them from the body.

Our immune system plays a potentially deadly mutation game to help us resist infection. To  keep up with invading viruses and bacteria, which rapidly mutate to evade detection and destruction, the cells of our immune system must mutate just as rapidly. Individual immune cells acquire DNA sequence changes hundreds or thousands of times faster than other cells in the body.

‘Bad mutations’ are an inevitable byproduct of these rapid mutations. Cells with bad mutations are more likely to multiply and form a rogue clone in response to the body’s own tissues.

Rogue clones can remain benign in the blood for decades, but they can also cause over 100 different autoimmune diseases, or can multiply wildly to cause leukemia, lymphoma or myeloma.

Using rapidly developing cellular genomics technologies, this research program will identify, via blood test, rogue clones from 32 different autoimmune diseases, including rheumatoid arthritis, autoimmune thyroid disease, Sjögren’s syndrome, systemic lupus erythematosus and multiple sclerosis, among others.

This research will identify bad mutations in these cells, and use sophisticated gene editing techniques to determine the cellular consequences of particular combinations of bad mutations for gene expression patterns in the rogue cells. These studies will pinpoint chinks in the armour of the rogue clones that could make them susceptible to new forms of immunotherapy or to new drugs that target specific immune cell pathways.

 

Representation of a rogue clone in the bloodRepresentation of a ‘rogue clone’ in the blood