Specialties

The lab is dissecting the effect of cholesterol depletion on the cellular pathways as demonstrated in figure 1. We are utilising a wide range of experimental assays to capture pathway dynamics in cancer cells during cholesterol-rich and cholesterol-depletion conditions both at gene level as well as protein level.

Cholesterol accumulation has been linked to cancer progression. We aim to elucidate the role of cholesterol in cancers and assess the use of cholesterol-depleting agents in treating drug-resistant cancer cells. We have identified, that depleting cholesterol in breast, colorectal and pancreatic cancer cells decreases cancer drug resistance in vitro and reduces tumour size in vivo (early, intermediate, and late stage breast and colorectal cancer). Our findings suggest that depleting excess cholesterol is a viable therapeutic strategy for the treatment of cancer. 

A variety of cell models are maintained in culture to predict the clinical effect of cytotoxic drugs and elucidate the role of cholesterol in proliferation and drug resistance. Various cancer, drug resistant and non-tumorigenic cell lines are currently maintained.

Organoid ex vivo cultures have revolutionized biological and medical research and proven to be an advanced model that more accurately replicate in vivo systems. Our lab is the first lab in South Africa to generate and establish intestinal organoids. Intestinal organoids are 3D structures that mimic the structure and function of the intestinal lining and are created by culturing intestinal stem cells in a specialized medium. Our team uses intestinal organoids to study the progression of colorectal cancer, its interaction with the immune system and the molecular mechanisms driving cholesterol-mediated drug resistance. The work with intestinal organoids is part of a larger effort to develop new therapies for intestinal diseases that are specific and effective, with the ultimate goal of improving patient outcomes.

A combination of statistical and computational tools is used to develop predictive models of drug resistance and cancer prognosis. In silico findings are validated experimentally in cell models and in future in patient samples. We are in the process of identifying novel biomarkers for use in the diagnosis and treatment of colorectal and breast cancer.

The current projects also involve developing a pipeline to efficiently analyses RNA-Sequencing data available in public domain as well as our own sequencing data focusing on patient samples. We refine existing methods and apply various tools to delve deeper into molecular mechanisms associated with cancer drug resistance and to delineate pathways linked to cancer progression from early to late stage and to metastasis. We have also developed a first-ever curated database of Inflammatory Bowel Disease.