Cancer

Design of Cholesterol Biosynthesis Inhibitors as Anticancer Agents

Primary Supervisor: Dr David Leaver
Co-supervisors: Dr Boris Budiono and Dr Ken Chinkwo
Location: Wagga Wagga
Keywords: cancer, cholesterol, enzymes
Study Availability: Available until December 2027
Research Group: Medical Sciences

Synopsis:
Much research over the last several decades has been focused on finding novel anticancer agents that inhibit cholesterol biosynthesis, however, there has been little to no success in this endeavor and the pharmaceutical industry is reluctant to pursue sterol biosynthesis inhibitor drug development. Over the last couple of years structural biology advances have enabled the crystal structures of post-squalene cholesterogenesis enzymes to be solved that can be used to design novel cholesterol biosynthesis inhibitors. This project will use a structure guided approach to discover new anticancer drugs that selectively inhibit cholesterol biosynthesis enzymes.

Crystal structures of enzymes in the post-squalene segment of cholesterogenesis A: Crystal structure of squalene monooxygenase bound with FAD (black) and “Cmpd 4” (blue), PDB 6C6N; B: Crystal structure of lanosterol synthase bound with lanosterol (black), PDB 1W6K; C: Crystal structure of Emopamil-Binding Protein bound with U18666A (red), PDB 6OHT; D: Crystal structure of sterol 14α-methyl demethylase bound with ketoconazole (red), PDB 3LD6. Figure adapted from Biochemical Pharmacology 2022, 196, 114611.

Interested? Start the conversation here by contacting Dr David Leaver

Evaluating Natural Product-Based Modulators for Cancer Therapy Using the Tumour-Induced Chicken-Egg Model

Primary Supervisor: Dr Ken Chinkwo
Location: Wagga Wagga
Keywords: cancer, chicken-egg, CAM assay, sorghum, antioxidants
Research Group: Food as Medicine (FAM) Research Group

Synopsis:

This project, led by Dr. Kenneth Chinkwo at Charles Sturt University, aims to revolutionize cancer study by developing a novel, cost-effective preclinical model using the Chicken Chorioallantoic Membrane (CAM) assay. By engrafting cancer cells such as colon, prostate, as well as canine osteosarcoma (OSA) cell lines onto the CAM, the research seeks to evaluate the therapeutic potential of polyphenolic compounds derived from sorghum and chickpeas, known for their potent antioxidant and anticancer properties.

This innovative approach addresses significant gaps in most cancers, including OSA treatments, but also offers a translational bridge to human oncology, as canine osteosarcoma closely mirrors its human counterpart. The project promises to provide foundational insights into tumor biology, angiogenesis, and metastasis while exploring natural therapeutic solutions with minimal toxicity. With a focus on reproducibility, ethical considerations, and real-time monitoring, this research has the potential to significantly advance both veterinary and human cancer treatment strategies, making it an exciting opportunity for students interested in cutting-edge cancer research and translational medicine.

ASBMB Biomolecular Horizon 2024 Poster

Interested? Start the conversation here by contacting Dr Kenneth Chinkwo

Exploring the anticancer potential of cereal and pulse phenolic extracts

Primary Supervisor: Dr Ken Chinkwo
Location: Wagga Wagga
Keywords: cancer, chicken-egg, CAM assay, sorghum, antioxidants
Research Group: Food as Medicine (FAM) Research Group

Synopsis:

Our study examines the anticancer properties of cereals and pulses, particularly focusing on the effects of phenolic extracts from sorghum, rice,
barley, oats, and chickpeas on SW480 and HT29 cancer cell lines. It highlights significant findings, such as the ability of these extracts to reduce cancer cellproliferation and promote apoptosis through the modulation of tumour suppressors and other genes. Additionally, it showcases the potential of these dietary compounds to inhibit cancer cell migration, indicating their broader health-promoting properties.

The research also outlines ongoing work, including a pilot project employing an in ovo tumor model to further explore the extract’s anticancer mechanisms, signalling a promising direction for future investigations into cereal and pulse bioactivity as potential therapeutic agents against cancer.

Link to research poster.

Interested? Start the conversation here by contacting Dr Kenneth Chinkwo