Tissue architecture and Organ Function Laboratory

Dr. Guillermo A. Gomez

Laboratory Head, Senior Research Fellow, Tissue architecture and Organ Function Laboratory

Centre for Cancer Biology, an alliance between University of South Australia and SA Pathology

Dr Gomez performed his BSci(Hons) in Chemistry (2004), PhD (2008) and first postdoctoral position (2008-2010) at the National University of Cordoba in Argentina, where he acquired experience in cell biology and quantitative image analysis. Then, during his postdoctoral training at the Institute for Molecular Bioscience, the University of Queensland, he implemented novel fluorescence microscopy technologies to study the mechanobiology of cell-cell interactions and how these contribute to tissue organisation in normal and pathological circumstances.

In 2017, He began his independent laboratory at the Centre for Cancer Biology, whose research focuses on Brain Cancer. His laboratory is well-known for its contribution to the development of organoid models for brain tumour research, cutting-edge imaging and computational approaches and artificial intelligence, to study fresh tumour samples. These developments led to the creation of new brain cancer research resources, permitting the identification of new molecular targets to treat brain cancer based on the tumour microenvironment.

Dr Gomez' scientific achievements are highlighted by >75 publications in the field of mechanobiology and brain cancer (Hindex=33, >3,500 citations, google scholar) and nationally competitive grans for >$8M. These include research articles in Nature Cell Biology (x3), Nature Communications, British Journal of Cancer and BMC Biomedical Engineering in where he is first or corresponding author and grants from the Australian Research Council (ARC Future Fellowship 2017-2020), The Cure Brain Cancer Foundation, The Charlie Teo Foundation and The Neurosurgical Research Foundation.

Amin Zadeh Shirazi

PhD Student, Gomez lab

A computer engineer with a background in Artificial Intelligence. The main focus of his bachelor’s project was on nano-scaled communication networks in the human body. During his master’s studies, he was able to propose and implement a novel hybrid intelligent algorithm for reliable detection of the stage of breast cancer malignancy based on mammography images radiomics and patients’ BIRADS information. This hybrid algorithm was a combination of two Machine Learning methods including Self-Organizing Map (SOM) for patients’ clustering and Complex-Valued Neural Networks (CVNN) for classification purpose. Before he started his PhD in Australia, he had been working as a data engineer and was able to successfully apply ML techniques to several industrial and biomedical projects. He then pursued his PhD in the Centre for Cancer Biology under the supervision of Dr. Guillermo Gomez, where the main focus of his PhD was the application of Artificial Intelligence to brain cancer. During his PhD, he learnt how to work, process, and analyse high-resolution H&E histopathology images of Glioblastoma patients by using Deep Learning algorithms. He has managed to publish 15 research articles (including 2 book chapters) in internationally recognized journals being the first author in 10 of them.

Kaitlin Scheer

PhD Student, Gomez lab

Following completion of her honours degree in 2012, Kaitlin worked for several years at the Centre for Cancer Biology, investigating changes to gene regulation networks and signalling in the tumour microenvironment that contribute to cancer cell survival and metastasis. More recently, Kaitlin joined the Gomez lab as a PhD student, where she is particularly interested in understanding the role of the perivascular niche in glioblastoma. For her project she is using a novel combination of bioengineering approaches to create a vascularised patient-derived organoid model. Her goal is to use this model to identify factors that are predictive of patient response to anti-angiogenic therapies.

Sally Perrin

PhD Student, Gomez lab

With a strong foundation in Psychological and cognitive Neuroscience sciences, Sally is passionate about interdisciplinary research to find new cures for glioblastoma. She joined the Gomez lab in 2018 to pursue her PhD studies exploring patient demographics and the biology of the tumour microenvironment in clinical treatments outcomes for patients with glioblastoma. Sally utilises cutting edge bioinformatic technologies and patient-derived brain tumour organoids for the identification and functional evaluation of new molecular targets for glioblastoma. Sally’s research aims to better stratify patients based on their demographic information, leading to improved clinical outcomes and survival for brain cancer patients.

Current research Projects

The Tissue Architecture and Organ Function Laboratory was founded in 2017 and headed since then by Dr Guillermo Gomez. Its main goal is in translational research in Brain Cancer through the identification of new molecular targets that inhibit key interactions between tumour cells and stromal cells in the tumour microenvironment that are important in mediating glioblastoma growth, invasion and resistance to therapy.

To achieve this goal our laboratory has pioneered cutting-edge approaches for the study of fresh patient-derived brain tumour samples that include:

• Culture and expansion of patient derived brain tumour explant organoids.
• High-content drug screenings in organoids using multimodal microscopy.
• Single cell RNA sequencing and spatial transcriptomics
• Artificial intelligence

The ability to perform deep studies on patient-derived tumour materials through the implementation of these new technologies is a paradigm shift in brain cancer research and is allowing us to:

• Interrogate and access information directly from the patient's tumour.
• Perform functional experiments in better and clinically relevant in vitro models for brain cancer.

Using these technologies is enabling us, for the first time, to functionally evaluate molecular targets and biomarkers during the preclinical stage for their future translation into clinical trials.

Projects.

1. Development of new AI and bioinformatics methods for the analysis of patient-derived diagnosis information to identify new molecular targets for glioblastoma and its functional test in patient-derived organoids. Studying the tumour microenvironment in brain cancer is incredibly complex – there are few tools at hand and significant variation in current experimental models. This project has two key game-changing aspects: (1) to use artificial intelligence to analyse vast volumes of existing tumour images not easily capable by humans and (2) using patient-derived explant organoids to re-create, cultivate and analyse the tumour in a 3D model called an organoid. This combination will enable the PhD or Honour student recruited to this project to combine AI and bioinformatics for the identification of new molecular targets for the development of new therapies for brain cancer patients and its functional test in organoids.
2. Development of a multidimensional atlas with single-cell resolution of gene, protein and metabolite expression for glioblastoma in patient-derived tumour tissue and matched organoids for identification of tumour-microenvironment interactions that drive glioblastoma progression. [in collaboration with Dr. Lisa Ebert (CCB), Dr. Rebecca Ormsby (FMC), Stuart Pitson (CCB), Santosh Poonnoose (FMC), Paul Trim (SAHMRI) and A. Prof. Marta Krasowska (UniSA)]. By accessing patient tissue samples and performing complementary and matched spatial transcriptomics (Method of the Year, 2020, Nature Methods), mass spectrometry imaging and atomic force microscopy analysis, this project, aims, for the first time, to characterise fundamental properties of glioblastoma tumour tissue with unprecedented resolution. The Honours or PhD student recruited to this project will contribute to generation of this multidimensional Atlas that will constitute a significant breakthrough in brain cancer research by enabling fundamental discoveries in glioblastoma biology that are critical to improve glioblastoma’s clinical management.
3. Harnessing brain tumour cell-blood vessel interactions as new therapeutic targets for recurrent glioblastoma. (in collaboration with Prof. Stuart Pitson). The interaction of the tumour cells with blood vessels in the brain that alter the properties of the tumour cells to make them both less responsive to therapy and also highly invasive into the surrounding healthy brain tissue. Moreover, the presence of the blood-brain barrier that limits the capacity of anti-cancer drugs to reach and kill highly invasive tumour cells within the brain. These characteristics make tumours of the brain resistant to almost all therapies, emphasising the need to better understand the biology of brain tumours so that new, more effective and personalised treatments can be developed. We have established advanced bioinformatics and artificial intelligence (AI) pipelines that, together, can extract unprecedented information on tumour-blood vessel interactions from cutting-edge single-cell analysis of the genes switched on in a patient’s brain tumour and vascularized in vitro models to functionally test these new targets. The Honours or PhD student recruited to this project will contribute to the characterization of the perivascular niche in glioblastoma using a combination of spatial biology approaches and patient-derived vascularized tumour organoid explants that will constitute a significant breakthrough in brain cancer research by enabling fundamental discoveries in glioblastoma biology.