Assoc Prof Guillermo Gomez

Senior Research Fellow Centre for Cancer biology

Current Positions:

• Head, Tissue Architecture and Organ Function Laboratory at CCB

Current NRF-funded projects include:

• Identification and targeting of the master regulators of glioma cancer cell plasticity to overcome therapy resistance in glioblastoma

Significant progress has been made in characterizing genetically and functionally diverse GBM subtypes as well as identifying the key oncogenic signals that drive their progression. However, this knowledge has not advanced clinical management of the disease. Indeed, the list of therapeutic agents in phase III and phase IV clinical trials for GBM reveals that only a few of the known GBM activated signalling pathways are currently being targeted in the clinical space. Lack of pipelines to translate fundamental knowledge into clinical trials, highlights the lack of systematic efforts to target intrinsically heterogeneous GBM tumours.

My laboratory combines expertise in patient derived glioblastoma tumour organoid models, bioprinting and bioengineering approaches with single-cell RNAseq, genome-editing, multiphoton microscopy and artificial intelligence, to develop physiologically relevant patient-derived pre-clinical assays that can be used for pre-clinical test of new therapies against glioblastoma as well as identify the molecular drivers of glioma stem cell plasticity and how they cooperate with the tumour microenvironment to develop resistance.

• Region-specific brain organoids for rapid and personalised pre-clinical test of treatments for glioblastoma

Glioblastoma (GBM) prognosis and treatment is profoundly affected by its anatomic location. Given the importance of tumour location and the microenvironment in GBM progression, there is an urgent need for the development of in-vitro models that facilitate the analysis of brain tumours in a more physiologically and relevant 3D setting. For this we will develop engineered synthetic hydrogel platforms to grow region specific human brain organoids to precisely model GBM progression in patient’s brain anatomical microenvironment. This will permit us to screen for drugs that stop tumour growth and invasion and identify the genes and pathways that drive these processes.

Guillermo Gomez is an ARC Future Fellow and a brain tumour researcher at the Centre for Cancer Biology – an alliance between SA Pathology and the University of South Australia. He is also a committee member for the newly formed, Brain Tumour Research SA.

Please tell me about your current research?

“In 2017, I began my independent laboratory at the Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia.

“The research focus of my independent work is 100% on Brain Cancer, specifically on the role of the tumour microenvironment and interactions between tumour cells and stromal cells on glioblastoma growth, invasion, and their mechanical and metabolic adaptation within the tumour niche.

“To do this, my laboratory has developed cutting-edge wet-lab and computational approaches. These include artificial intelligence (AI), single-cell and spatial transcriptomics to study fresh patient tumour samples and the growth of patient-derived brain tumour organoids that better replicate the physiology and architecture of the primary tumour,” Guillermo said.

Why is funding for brain tumour research so important?

“While the survival rates of most cancers have dramatically improved in the last few decades, this is not the case for brain cancers, where the 5-year survival has hardly changed for 30 years, remaining around 20%. For glioblastoma, the most diagnosed malignant brain cancer in adults, the statistics are far worse, with a 5-year survival of just 5% (Health and Welfare, 2017).

“Despite recent advances in understanding some of the critical drivers of glioblastoma formation and progression, this knowledge has not yet translated into improvements in glioblastoma therapy. This lack of progress in the clinical setting is mainly due to the highly heterogeneous nature of glioblastoma, and the ability of tumour cells to switch transcriptional programs in response to the interactions with cells in the tumour microenvironment leads to therapy resistance and tumour recurrence.

“Thus, targeting the interaction of tumour cells with non-malignant cells in the tumour microenvironment has recently emerged as an exciting anti-cancer approach in glioblastoma. However, we are right at the beginning of understanding how tumour-stroma interactions favour the tumour. More research in this space is critical to identify new targets for better and more personalised therapies for brain cancer,” he said.

Why did you join the committee for BTRSA?

Guillermo explains, “My laboratory has developed the capacity and skills to combine and integrate different fields critical for today's brain cancer research to find a cure for brain cancer.

“This aligns with the spirit of the Brain Tumour Research SA and its collaboration with the NeuroSurgical Brain Tumour Bank and the NeuroSurgical Research Foundation, to accelerate translational research that permits to interrogate large datasets of clinical information, genomics and single-cell data using AI.

“This allows the identification of new biomarkers and molecular targets that can rapidly transition into early stages Brain Cancer Clinical Trials if successfully tested in cutting-edge patient-derived organoids,” he said.

Why did you become a researcher and what is it that drives you?

“I decided to become a researcher after a research experience in a neuroscience lab, when I was in Year 12.

“I always love physics, chemistry, and maths, but working in a neuroscience lab and performing electrophysiology experiments show me a bit about the complexity of Biology. However, my mentor at that time, makes me realise that if we were to make significant contributions as a scientist, these would occur if I can innovate and give a new view to biological problems. I took his advice. I did my undergraduate in Chemistry, taking courses on maths, physics, quantum chemistry, computational modelling, cell biology and immunology, with the idea that I can bring this know-how to do innovative biology research.

“After my undergraduate, I did my PhD in cell biology, where the most important tool was microscopy. At that moment, I became fascinated by the biology of single cells and writing scripts for automated analysis of images. In my postdoc, I took a step further and studied the mechanobiology of multicellular tissues. I become fascinated by generating knowledge that permitted a better understanding of how cells sense and generate physical forces.

“Over these years, I developed a significant armament of techniques and expertise in different research fields that reached the right momentum to provide new hopes for a brain cancer cure.

“My goal is to generate knowledge that leads to a better understanding of the biology of brain tumours and put this forward to develop new and better therapies to cure brain cancer by 2030, Guillermo said.