Catherine WM Ong

My laboratory focuses on 3 areas of translational Infectious Diseases research:
1. Host-pathogen interactions
2. Biomarker discovery
3. Host-directed therapies
Under the theme of host-pathogen interactions, my lab investigates the effect of Mycobacterium tuberculosis (M.tb) on the secretion of human proteases from host cells which can cause tissue destruction and cell death. There are 5 distinct classes of proteases which are classified by the mechanism of catalysis: aspartic, metallo, cystein, serine and threonine proteases. We profile proteases in the sputum of active TB patients, and investigate host proteases in TB disease including central nervous system TB to evaluate tissue destruction. My lab also focuses on the regulation of these proteases from host cells including mononuclear cells, neutrophils, and parenchymal cells. Intracellular signalling pathways such as the MAP-kinase, PI3 kinase and transcription factors such as NF-kB and AP-1 will be investigated to determine if there are switch points by which potential therapeutic agents can be administered to suppress the detrimental effects of human proteases on TB-associated tissue destruction.

Under the theme of biomarker discovery, my lab focuses on identifying M.tb circulating cell-free DNA (cfDNA) in TB patients, a project which has received funding for the generation of pilot data. cfDNA is circulating DNA fragments from degenerating cells found in body fluids including blood and urine. We are investigating the presence of M.tb cfDNA in clinical samples such as plasma, urine and oral secretions of active TB patients and use latent TB and non-TB patients as controls. This proof-of-concept study will evaluate M.tb cfDNA to detect and monitor bacterial load in TB patients by clinical samples obtained by non-invasive means. Pilot data generated will provide the platform to a Phase II study to validate its use in large cohorts of pulmonary and extrapulmonary TB including the immunosuppressed (eg. HIV patients). More recently, we have embarked on rapid pathogen and antimicrobial resistance detection, and embarking on developing a microfluidic device that can become a point-of-care device for diagnosis of bloodstream infections.

Under host-directed therapies, my lab explores existing drugs that have potential to modulate TB treatment outcome. We investigate a variety of re-purposed drugs, as an adjunct therapy to TB treatment by randomised-controlled Phase 2/3 trials. We also have a murine model of central nervous system-TB to investigate the role of proteases and neutrophil extracellular traps in mechanisms of tissue destruction in CNS-TB. This model would provide preliminary data for potential therapies to be tested in human TB patients in the future.