Tackling global health disparities through transdisciplinary research

It was with great pleasure that I accepted an invitation from the Australian Society for Medical Research to speak at their National Scientific Conference in November. I am truly excited to be coming to Australia (for the first time!) and I’m looking forward to being inspired by some of your best scientists and establishing new research collaborations.
The work my team and I conduct brings together engineering, cell biology and physiology to understand how cells sense, respond, and remodel their immediate mechanical and biochemical environments for repair and regeneration. Our work doesn’t stop there: our ultimate goal is to translate our findings to clinics domestically and internationally to impact global health disparities.

In this brief blog post I wanted to highlight some of the transdisciplinary work my group has been doing in HIV/AIDS research. While most people realise that the highest incidence in this disease is in sub-Saharan Africa, many are not aware that the rates are not too different for African-Americans in the United States. Highly active antiretroviral therapy (HAART) has transformed HIV-infection from a terminal diagnosis to a manageable chronic disease. HIV-infected individuals, however, have shown elevated incidence of heart attacks and strokes. This has even been reported in adolescents who were born with HIV and on ART from birth! Our work seeks to study human cardiovascular events due to HIV infection, and to use animal native artery studies to guide tissue engineered strategies and parse mechanisms that are viral protein mediated from those due to antiretroviral medication side effects. At the same time, as biomedical engineers, we also take into account the influence of mechanical forces (shear stress and blood flow) as well as biochemical mediators that all control cell behaviour.

We’ve also been addressing the need to develop affordable and reliable markers of adherence to antiretroviral therapy (ART), particularly for resource limited settings such as those in South Africa and Ethiopia. This is extremely important to determine which patients are no longer responding to therapy, and will have other applications as pre-exposure prophylaxis (PrEP) rolls out to protect HIV-negative individuals at high risk from contracting the virus. Cost will be an important factor to regularly monitor patient adherence. We are currently trialling a system using our cathepsin zymography assay to monitor ART adherence, instead of the currently expensive method of mass spectrometry, or the inexpensive but error-prone method of patient surveys. Working with Dr Denise Evans at the University of Witwatersrand in Johannesburg, South Africa, we have been tracking cathepsin activity in white blood cells from the day of diagnosis to 6, 12, and 24 months out in the same patients while they (hopefully) take their antiretroviral drug ‘cocktail’ regularly. These patients usually have had their cathepsin levels drop after either the six or twelve-month period, and has been a strong indicator of adherence using viral load as the gold standard. This is an excellent example of engineering, biochemistry, technology, AND epidemiology all converging to find solutions to difficult, but impactful problems. Watch this space!

I look forward to meeting many of you in Melbourne soon. All the best,

Manu O. Platt


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