Associate ProfessorKimberley Alexander

Blood 'fingerprinting' for accurate glioblastoma diagnosis and surveillance

Investigators:A/Prof Kimberley Alexander, Dr Susannah Hallal, Dr Matin Ramezani, Dr Laveniya Satgunaseelan, A/Prof Hao-Wen Sim, A/Prof Brindha Shivalingam, A/Prof Fatemeh Vafaee

We have developed a novel strategy that uses artificial intelligence and advanced molecular profiling of nanoparticles captured from the blood. We tested this using 100+ glioblastoma blood samples and discovered a 'bloodfingerprint'that can detect tumour recurrence with 93.4% accuracy. With access to an additional 386 blood samples and clinicopathologic data collected from 104 glioblastoma patients, we aim to confirm the recurrence blood fingerprint and test its clinical impact in glioblastoma trials. Mapping blood fingerprints as they change over the glioblastoma clinical course will allow us to assess whether our approach can support personalised treatment decisions to improve patient outcomes.

Confirming highly sensitive 'liquid gold' biomarkers for detecting glioblastoma and monitoring recurrent progression.

Investigators:A/Prof Kimberley Alexander, Dr Susannah Hallal, Ms Kasuni Gamage, Dr Matin Ramezani, Dr Laveniya Satgunaseelan, A/Prof Hao-Wen Sim, A/Prof Brindha Shivalingam,

Glioblastoma releases large numbers of extracellular vesicles (30-1000nm nanoparticles) into the circulation. As EVs are cleared from the body via the urinary system, we tested the feasibility of monitoring urine-EVs as a practical and readily implementable, non-invasive biomarker. We performed high-resolution quantitative mass spectrometry (DIA-LC-MS/MS) onurine-EV proteomes from 24 glioblastoma patients, including specimens collected before/after primary tumour resection and at recurrence, plus 14 age/gender-matched controls. Among the highly significant findings was a panel of five urine-EV proteins that corresponded to a glioblastoma diagnosis with a combined performance accuracy of 95.8%, and two urine-EV proteins predictive of glioblastoma recurrence with 100% accuracy.We aim to validate our biomarker panels in a further 130 purpose-collected urine specimens to determine the clinical utility of a 'liquid gold biopsy'for glioblastoma.

New ultra-fast brain tumour diagnostics: reducing anxious wait times for patients and putting treating doctors on the front foot

Investigators:Dr Laveniya Satgunaseelan, A/Prof Kimberley Alexander, A/Prof Hao-Wen Sim, A/Prof Brindha Shivalingam, A/Prof Michael Buckland

There are more than 100 different types of brain tumours. Determining the exact type of brain tumour is critical to selecting the best treatment for the patient. Pathologists diagnose brain tumours by looking at tissues under the microscope and then performing a series of genetic tests. These tests take 2-6 weeks to report a complete diagnosis. This wait time can be incredibly distressing for patients and can delay urgent treatments. We aim to revolutionise brain tumour diagnostics in Australia, offering comprehensive diagnoses immediately after surgery rather than weeks later in a doctor's office. We recently acquired a cutting-edge 'Oxford Nanopore MinION' device, which was used during the pandemic to identify new COVID variants in low-resource countries. Powered by advanced artificial intelligence and the size of a smartphone, the MinION uses long-read gene sequencing technology to provide a detailed molecular profile of brain tumours. Our study will compare standard diagnostic methods to MinION long-read sequencing using 120 brain tumour samples stored in the Sydney Brain Tumour Bank. We aim to adopt this new technology in routine brain tumour diagnostics so patients can begin the most suitable treatment as soon as possible. New low-cost, ultra-rapid brain tumour diagnostics processes will be implemented through our partnership with the Neuropathology Department at Royal Prince Alfred Hospital, Australia's leading brain tumour diagnostics centre, and shared with other health districts and states to benefit all brain cancer patients in Australia.

3D bioprinting with glioblastoma 'ink': engineering patient-specific brain tumours for high throughput drug screening and individualised therapy

Investigators:Professor Jeremy Crook, A/Prof Kimberley Alexnader, Dr Eva Tomaskovic-Crook, Dr Laveniya Satgunaseelan, A/Prof Brindha Shivalingam, Dr Hao-Wen Sim, Professor Lenka Munoz

Effective treatment options for patients diagnosed with aggressive glioblastoma are urgently needed.We aim to establish a new precision-care pathway for glioblastoma patients at the Chris O'Brien Lifehouse. This highly innovative proposal will bring together multiple established and flagship Lifehouse programs for the first time - including neurosurgery, brain cancer research and fresh tumour biobanking, pioneering tissue engineering and 3D-bioprinting, novel drug discovery, and clinical trials.

3D-bioprinting allows the rapid fabrication of highly versatile living tissue constructs. We will harvest fresh glioblastoma tumour material directly from neurosurgical theatres and introduce disaggregated cells to a bioprinting 'ink' that mimics the physico- and physio-chemical cues of neuronal tissue extracellular matrix.High throughput printing of 'glioblastoma-ink' into 96-well plates will rapidly generate uniform arrays of 3D tumour spheroids. By directly comparing parent and 'printed' glioblastoma tumours, we willassess the extent to which morphological and molecularcharacteristics are maintainedin vitro.Printed glioblastoma tumours will be in an ideal format for new and repurposed drugs, including panels of novel brain penetrant small molecule inhibitors, to be safely and efficiently screened.Discoveries will be fast-tracked to clinical trials leading to tangible survival benefits and improved quality-of-life for patients.

Stopping GBM before it starts: tumour initiation events and molecular drivers of glioma progression

Investigators:Dr Laveniya Satgunaseelan, Dr Justin Wong, Dr Gavin Sutton, A/Prof Kimberley Alexander, A/Prof Mainthan Palendira, A/Prof Hao-Wen Sim, A/Prof Brindha Shivalingam

Lab-on-a-chip diagnostics:fabricatinga point of care urine test for brain cancer

Investigators:A/Prof Kimberley Alexander, Prof Arnold Ju, Dr Mingxin Xu, Dr Susannah Hallal, Dr Laveniya Satgunaseelan, A/Prof Hao-Wen Sim, A/Prof Brindha Shivalingam