Anu Thomas Koikalethu
Queensland University of Technology
Bone & Tumour Engineering
Abstract
Breast cancer is the most frequently diagnosed cancer globally and the most prevalent cancer in women affecting millions each year. It is a highly heterogenous disease, making patient-specific information critical in the clinical decision-making process and in determining patient outcomes. This creates an urgent need for personalized breast cancer models.
The Bone and Tumour Engineering Group at Queensland University of Technology (QUT) focusses on developing three-dimensional (3D) cancer and bone models. Within the group, my research aims to develop personalised testing platforms for breast cancer using 3D models that effectively recapitulate the breast tumour microenvironment on a patient-specific level. These models will be used for evaluating drug sensitivity and combinational therapies that would yield vital information, thus aiding clinical decisions of patient treatments. Furthermore, bone mimicking models will be developed to investigate the dysregulated pathways between the breast and bone which results in metastasis.
Developing 3D models using patient-derived organoids and cells requires optimisation of scaffold materials, growth medium, and cell co-culture conditions to maintain the native cellular properties. To maintain the native properties of patient-derived cells, protocols for isolating cells from patient tissue and culture media for subsequent cell maintenance were optimised. Cellular phenotype was validated by immunofluorescent staining of cytokeratin, vimentin and hormone receptors. This demonstrated preservation of phenotype in of the cancer and fibroblastic cells of the tumour. The mechanical properties of substrates for mimicking the extracellular matrix (ECM) were characterised by compressive testing. Gelatin based hydrogels could be tuned to obtain a substrate with a dynamic range of Young’s moduli between 0.5 - 4 kPa, which most closely matched the stiffness of native breast tissue which is about 1 – 3kPa. The cytocompatibility of these materials have also been assessed by measuring the metabolic activity and viability of the cell-laden biomaterial. Significant differences in growth of organoids with regard to different ECM mimicking substrates were observed. These organoids were then subjected to drug testing, and the response was evaluated using a luminescent cell viability assay, revealing differences in drug sensitivities between patients, which further emphasised the need of tailored drug testing platforms.
We have also successfully engineered mineralised scaffolds containing cells of the bone microenvironment to mimic the bone microenvironment. The cell-laden scaffolds were characterised by evaluating the presence of bone microenvironment specific indicators through immunofluorescent staining, scanning electron microscopy and enzyme linked immunosorbent assay (ELISA), among several other assays. Efforts to automate these models, by using bioprinting technology, are ongoing. Preliminary experiments are being carried out to identify the ideal bioink for the platform.
From a young age, I was captivated by the workings of the human body. My first venture into cancer research began when I opened fifty tabs on Google, delved into articles from WebMD and Mayo Clinic about cancer, after a close family member’s diagnosis. This early experience ignited a commitment to cancer research. It continues to drive my passion to make a meaningful contribution to the fight against cancer and support those affected by it.
Kamal Ranadive. She was iconic for her work in cancer research which gave crucial insight into the role of viruses in cancer. As a pioneering woman scientist in India, she defied societal norms and elevated the status of women in science by creating a legacy. Even after her retirement, she trained women in healthcare and provided health and nutrition education in rural communities.
Inquisitive, Persistent and Compassionate
I speak five languages and am always working to add more to that list. I enjoy travelling and learning about different cultures and their history. When I’m not conducting experiments in the lab, you can find me carrying out culinary experiments in the kitchen.
Awards
1st Place
The Grand Prize recipient from each participating country wins a trip to Promega headquarters in Madison, WI USA to meet our R&D team, present their project and network with fellow award recipients.
Public votes are cast between 15 October - 15 November 2024 for each nominee. The candidate with the most votes wins.
Runner Up Awards
Four remaining Finalists will each receive a limited edition Promega Lab Set with LEGO® Elements and a Duffel Bag
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Recipients Announced
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(Grand prize trip to Madison, WI to meet our R&D)
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