Understanding the molecular basis of how SMCHD1 deficiency accelerates blood cancer progression

Lead researcher

Dr Kelan Chen

Dr Kelan Chen

Institution

Walter and Eliza Hall Institute of Medical Research

Tumour type:

Blood Cancer

Years funded

2016

Project description

Epigenetic regulation is a process that dictates how genetic information encoded in DNA is read by cells. In short, the epigenetic information i.e. chemical tags laid down onto the DNA, instructs the cells when genes should be switched on to make their protein product or switched off. This process is critical for development and commonly goes awry in diseases.

My research focuses on revealing the structure and funcation of a protein known as SMCHD1, which is fundamental to understanding how it interacts with DNA and elicits epigenetic control. 

By probing the structure of the protein, we will be able to develop chemical tools that alter its function. These chemical tools will serve as useful reagents that allow us to investigate if we can manipulate SMCHD1 protein in cancer progression, and ultimately inform the development of new therapeutics for blood cancer. 

What is the need? 

It has been previously shown that the epigenetic regulator protein, SMCHD1, is implicated in cancer where deficiency of SMCHD1 could accelerate the progression of blood cancer.

Interiguingly, defects in SMCHD1 are also linked to an incurable muscular disorder called facioscapulohumeral muscular dystrophy (FSHD) while enhanced SMCHD1 function appears to cause the congenital disorder Bosma arhinia microphthalmia syndrome (BAMS).  

However, it is unclear how SMCHD1 functions at the molecular level and whether manipulating its function could be exploited for therapy. 

What impact will this research have?

By understanding more about the role of SMCHD1 protein, we can work out if manipulating it will lead us to develop new treatments for a range of disease types, including blood cancer.


"These chemical tools will serve as useful reagents that allow us to investigate if we can manipulate SMCHD1 protein in cancer progression, and ultimately inform the development of new therapeutics for blood cancer."