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Dr Jessica Holien

Postdoctoral Fellowship

Funded in Partnership with Cure Cancer Australia Foundation

Researcher:          Dr Jessica Holien
Institute:                St Vincent's Institute of Medical Research
Project title:          Designing anti-leukaemia drugs
Disease focus:      Leukaemia
Annual Funding:   $100,000
Funding period:    2014-2016

Funded in Partnership with Cure Cancer Australia Foundation 

Project summary 

Dr Jessica Holien is leading a project to develop therapeutics for treating leukaemia. The potential new drugs will target two separate protein-protein interactions, involving Homeobox (HOX) and the 14-3-3 proteins.

Several HOX proteins are overexpressed in leukaemia and are thought to contribute to blood cancer development. These proteins interact with both DNA and protein co-factors to control leukaemia cell survival. In a similar way, the 14-3-3 protein interacts with specific proteins to promote leukaemia cell expansion.

By modelling the three-dimensional shapes of HOX and 14-3-3 interacting with key proteins, Dr Holien can identify possible drug targets. With this knowledge, it is possible to design novel compounds that specifically target and disrupt the complexes.

According to Dr Holien, protein-protein interactions (PPIs) like these are important for regulating healthy blood cells and are often effected in leukaemia.

“I’m working on novel ‘druggable pockets’ we’ve identified in the structural models of three HOX protein family members and the 14-3-3 protein,” said Dr Holien.

“To discover molecules that target HOX protein-protein interactions, I’m developing new tools in structure-based computational molecular modelling which we will use to develop drugs specific to blood cell cancer protein targets.”

In addition, Dr Holien has also identified several promising small molecules that target 14-3-3. In preliminary studies, these molecules blocked 14-3-3 in chronic myeloid leukaemia cells, leading to cell death.

Dr Holien is completing her Postdoctoral Fellowship in the Structural Biology Laboratory at St Vincent’s Institute of Medical Research in Melbourne. The Laboratory specialises in determining the three-dimensional atomic shapes of proteins involved in cancers.