Growing vessels from blood to predict transplant-associated cardiovascular disease

Doctor Mark Allenby, The University of Queensland

Future Leader Fellowship - Level 1

Years funded: 2025 - 2029

The use of stem cell and solid organ transplants is growing rapidly, saving 200,000 lives in 2024, but each transplant runs the risk of life-threatening rejection from the cardiovascular system. Endowed with immune response factors, our cardiovascular system represents a critical line of defence separating foreign invaders circulating our blood from our body’s organs. Activation of our cardiovascular defence system is useful in fighting pathogens but can become fatal during transplant-associated thrombotic microangiopathy (TA-TMA).

In TA-TMA, endothelial cells and hematopoietic cells see each other as invaders, creating a prolonged storm of inflammatory attacks on one another, causing microvessels throughout our body to become blocked, leading to multi-organ failure and death. TA-TMA is challenging to diagnose as it resembles the acute transplant response. As a result, TA-TMA is identified dangerously late with mortality rates up to 86%. Late TA-TMA detection also hinders clinical trials of new therapeutics, so that no treatment exists.

This proposal establishes the first diagnostic TA-TMA model to predict patient transplant rejection risk, optimise their transplant management, and evaluate promising treatments. I have led my research team to establish the first microcapillary-hematopoietic cell culture derived from one or two donors (auto- or allo-transplant) to model TA-TMA cytokine release, microthrombi formation, and inflammatory cell production. In this proposal I characterise, clinically validate, then apply my innovative diagnostic model to screen TA-TMA risk factors, management, and treatment options.

This proposal creates broadly useful cardiovascular research technology. Endothelial-hematopoietic dysfunction leading to blocked blood microvessels is a dangerous outcome of COVID-19, Berger’s disease, traumatic brain injury, and heart attacks. I am uniquely suited to lead this proposal, a young Senior Lecturer with leading international experience in hematopoietic and vascular tissue engineering, I am well-supported by my industrial (Red Cross) and clinical partners (RBWH) to translate our discoveries into lifesaving cardiovascular diagnostic models.