Research
Research areas
a) Disease modelling and drug discovery
Chronic stress and/or inflammation underpins the majority of modern diseases. Our group studies the dysregulation of regulatory systems (nervous, immune, endocrine, microbiome), in the context of non-infectious chronic inflammatory disease.
Our multidisciplinary, bench-to-bedside approach entails:
- Profiling disease in human cohorts, in collaboration with clinician collaborators
- Modelling disease in cell culture, rodents and/or zebrafish
- Drug discovery
- Optimization of drug delivery
- Pre-clinical evaluation of experimental strategies for benefit and risk
- Clinical trials
Current focus areas:
- Fibrosis-associated complications of systemic lupus erythematosus (SLE)
- Anxiolytic drug discovery and/or efficacy testing
- Gut-brain communication (in irritable bowel syndrome and autism spectrum disorder)
- Mitochondrial functional maladaptation in chronic inflammatory disease
- Adipose tissue signalling and accelerated ageing in chronic inflammatory disease
b) Diabetes and regenerative medicine
Type 2 diabetes mellitus (DM) is a global epidemic and is listed as one of the top five contributors to mortality in South Africa. The pathogenesis of DM is multifactorial, and the failure of inflammatory control mechanisms within adipose tissue, bone marrow, and peripheral blood mononuclear cells (PBMCs) have been implicated in disease progression. The combination of hyperglycemia, accumulation of advanced glycation end products (AGEs), and oxidative stress-induced DNA damage result in immune dysregulation (metabolic inflammation) and widespread cellular dysfunction; these are contributing factors in the development of comorbidities and poor clinical outcomes in general.
This group's research therefore focuses on elucidating cellular and molecular therapeutic targets in and assessing the efficacy of novel biological therapies, with a specific focus on diabetic wound healing. Research studies involve a variety of preclinical and clinical models and the use of stem cells, immortalised and primary cells, murine models of obesity / diabetes, as well as specific cohorts of patients.
Current focus areas:
- Cellular dysfunction: Understanding the underlying molecular mechanisms involved in the functional decline of mesenchymal stem cells in diabetes.
- Regeneration in health & disease: understanding the dysregulated healing responses in diabetic wounds
- Novel therapies: assessing the efficacy of novel regenerative strategies.
Zebrafish husbandry and research unit
Zebrafish has become increasingly important as research tool in health-related sciences. Their relatively low housing cost, high fecundity, transparent early life stages and high homology with human physiology, as well as the ease by which they may be genetically manipulated, makes them versatile and desirable for many different applications.
The zebrafish husbandry and research unit was founded in 2020, as a satellite unit of the Faculty of Medicine and Health Sciences research animal facility. The unit is GMO registered with DALRRD and all staff are SAVC-authorized para-veterinarians. We manage zebrafish husbandry and supply eggs to researchers across faculties and campuses.
The unit also supports a vibrant postgraduate cohort. We enthusiastically invite collaboration – please contact Prof Smith directly (csmith@sun.ac.za). Please refer to the “Disease modelling and drug discovery" link for more specific information on research activities using this model.