Investigating the molecular pathogenesis of genetic variants and developing corresponding therapies for eye diseases is the next project for PhD graduate Dr Di Huang.
Dr Huang undertook her PhD as a member of the Molecular Therapy Laboratory at the Centre for Molecular Medicine and Innovative Therapeutics (CMMIT) at Murdoch University.
Her project focused on applying antisense oligonucleotide (AO) technologies to develop treatments for Stargardt disease (STGD1). STGD1 is a rare and progressive genetic eye disease causing vision loss and eventual blindness for which there is no approved treatment.
To identify potential AO therapeutics, Dr Huang established an assay (test) using skin cells obtained from patients with STGD1 to investigate the consequences of variants of ABCA4, a gene known to cause STGD1. To further validate this, she also developed a stem cell model using patient-derived skin cells, providing novel insights into the pathogenesis of STGD1.
“Our lead antisense oligonucleotide candidate has the potential to halt the progression of vision loss for an estimated 200 patients carrying the ABCA4 variant c.[5461-10T>C;5603A>T] in Australia,” she said.
During her PhD, Dr Huang published seven papers, six as the first author. She also received multiple prizes for 3-minute Thesis competitions, including Virtual Asia-Pacific.
Her supervisors were Professor Steve Wilton (principal supervisor) at CMMIT and Perron Institute, Professor Sue Fletcher at PYC Therapeutics and Murdoch University, Associate Professor Fred Chen at Lions Eye Institute (LEI) and UWA, Dr May Aung-Htut at CMMIT, and Dr Sam McLenachan at LEI.
Dr Huang is currently working with A/Professor Chen and Dr McLenachan at LEI as a Research Associate, developing a powerful platform of retinal organoids (3D tissue structures) using induced pluripotent stem cells (from skin or blood cells obtained from patients with inherited eye diseases).
For her PhD journey, Dr Huang acknowledges many people who have supported her, firstly the Perron Institute and Murdoch University for providing her PhD Scholarship.
“I’m also sincerely grateful to my amazing supervisors, Steve, Sue, Fred, May and Sam, and my family for being there for me. As well as both labs for their support.
“I would like to acknowledge that this work was funded by the National Health and Medical Research Council of Australia, the Telethon Perth Children’s Hospital Research Fund and the Macular Disease Foundation Australia, and generous donations from the Saleeba, Miocevich and McCusker families. I also recognise the support from the Australian Inherited Retinal Disease Registry and DNA bank, Ling Hoffmann for collection of familial blood samples, PYC Therapeutics and the Centre for Microscopy Characterisation and Analysis affiliated with UWA.
“My PhD has taught me many valuable qualities, including resilience, perseverance and self-encouragement. I’ve learnt that failure is an opportunity to grow.
“My advice to students and young researchers is to remember that after you stumble, get up and try again. Not only in research, but in life.”
Congratulations, Dr Huang.
Photo caption L-R: Prof Steve Wilton and Dr Di Huang at CMMIT.