TCRN PhD Spotlight Series - Lachlin Vaughan

10 July 2019

For patients with a blood cancer called myelodysplastic syndrome (MDS), the future is bleak. The disease brings with it a raft of health complications, such as anaemia, potentially fatal infections, or blood that won’t clot. It also has a propensity to evolve into acute leukaemia – a transition responsible for the majority of MDS-related deaths.

The only cure for this disease is a bone marrow transplant – but in a cruel twist, the advanced age of many MDS patients means they’re ineligible for the procedure. Instead, their last hope is a non-curative drug called 5-Azacytidine (AZA), which typically adds up to two years to the average MDS prognosis. Even then, there’s a catch: only about 50 per cent of MDS patients respond to AZA at all.

In the midst of these challenges is a new research project that aims to improve treatment approaches for MDS. Conducted by TCRN-supported PhD student Lachlin Vaughan in the Stem Cell Group at UNSW, the work is trialling two new drug regimens aimed at patients who are unresponsive to AZA.  

“Research that was done by my group prior revealed why certain patients respond to AZA and others don’t. Those who don’t respond have an up-regulation of a key protein, which stops AZA from doing its work by not allowing it to incorporate into DNA,” says Vaughan.

“My research is focusing on inhibiting the function of that protein, and another sister protein, using two inhibitor drugs in combination with AZA.”

To date, Vaughan has shown that these drug combinations are effective in transforming cell function in blood stem cells that are dysplastic – that is, stem cells that fail to produce adequate numbers of functional red or white blood cells, or platelets that help blood clot. 

“Initially, these stem cells look like they’re very dysplastic and they don’t function adequately, but with this combination treatment the function of these stem cells improve,” Vaughan says

“It would seem from my research that by inhibiting these resistance pathways in blood stem cells, you can re-sensitise these patients to this treatment. The hope is that once I get a more definitive answer from some more downstream analysis in my research, we can show that this combination is effective.”

The project comes at a critical time for MDS research. Given that the disease typically affects patients who are 50 years and older, diagnoses are expected to increase as Australia’s population continues to age.

If successful, the as yet unpublished work could lead to a clinical trial of these inhibitor drugs, with the potential for their eventual translation into a clinical setting. This would represent a substantial breakthrough in MDS treatment outcomes – currently, patients who don’t respond to AZA tend to live for less than six months from diagnosis.

Before he embarked on a PhD, Vaughan was in the final stages of a haematology traineeship. An initial experience of research during a pathology fellowship piqued his academic interests; this project, under the supervision of Professor John Pimanda and Dr Ashwin Unnikrishnan at UNSW, solidified it.

Today, Vaughan is in his final year of study. And, while he’s mostly focused on getting to the finish line, he’s already thinking about how he might maintain a research profile once he returns to the clinical setting. 

“I haven’t completely figured out what I’m going to do once I’ve finished my PhD and in terms of how I would potentially balance research and clinical work, but ideally it would be fantastic to continue doing both,” he says.