Alexandra Sharland: Thompson

The Thompson Fellowship came at just the right time for Alexandra Sharland, giving her research into transplantation tolerance the added boost it needed. The Fellowship helped Sharland secure a national competitive grant, employ research staff and explore other avenues of research.

By Tim Groenendyk

Alexandra Sharland

“The Thompson really tipped the balance for me: from a person with good ideas who was almost successful to someone actually achieving success." Dr Alexandra Sharland

“I was at the point where we had great ideas, a great model, and there was a lot we could achieve but there’s only just so much you can do by yourself.

“The Thompson really tipped the balance for me: from a person with good ideas who was almost successful to someone actually achieving success. It was a real leg up.”

Dr Alexandra Sharland works in two main areas within transplantation.

The first area involves understanding how transplantation tolerance occurs.

“Most of the time a transplant between two individuals who are genetically different is going to be rejected.

“But there are some circumstances where the recipient’s immune system learns to accept the graft as ‘self’ – and that situation is called transplantation tolerance.

This situation is highly desirable; not only because it means the transplant has a better chance of long term success but also because the recipient is not reliant on a lengthy course of immunosuppression – which can result in opportunistic infections and increases the likelihood of the recipient acquiring various lymphomas and non-melanoma skin cancer.

“Immunosuppression has been of enormous benefit to the outcomes in the short-term after transplantation.

“But the outcomes in the long-term after transplantation are not a lot better than they were ten or fifteen years ago.”

“To avoid all the side-effects and consequences of life-long immunosuppression for patients, we need to better understand what to manipulate around the time of transplantation to achieve tolerance.”

Sharland’s other main area of research aims to understand how events that occur around transplantation damage the graft - and what interventions can be attempted to reduce or prevent negative consequences.

Events occurring around the time of donor death, organ storage, and the procedure of transplantation into the recipient can all lead to damage of the graft.

Sometimes this damage is so great that the organs cannot be relied upon to function properly after transplantation, and are thus not utilised. Even lesser degrees of graft injury make rejection more likely to occur and tolerance more difficult to achieve.

“If we could find a way to optimise the condition of those organs, and prevent further damage occurring, we would be able to expand the number of organs available from the existing pool of donors.”

In both these areas Sharland’s team employs a gene transfer technique which introduces genes into the liver of the recipient to express desired proteins.

The liver, Sharland explains, is very good at expressing high levels of proteins. Additionally, the immunological properties of the liver enable the introduced genes to be tolerated without provoking an immune response.

The Thompson Equity Fellowship funded a research assistant, Moumita Paul, who has played a vital role in the labour-intensive process of producing large amounts of gene transfer vectors.

Shortly after Sharland was awarded the Fellowship she received a grant from the Heart Foundation for a project focusing on heart transplantation.

This Grant-in-aid allowed Sharland to recruit a postdoctoral scientist, Eithne Cunningham, and - buoyed by the Thompson fellowship - she was able to generate preliminary data to secure a 3 year NHMRC project grant researching kidney transplant tolerance.

The Thompson fellowship also permitted Sharland to pursue research outside transplantation and contribute to the Charles Perkins Centre’s recent book on sustainable health - A Modern Epidemic: Expert perspectives on obesity and diabetes.

“Writing the chapter made me think about the pathogenesis of diabetes much more than I had previously.

“There are certain parallels between autoimmunity and transplantation: it might be possible to use the same kind of gene transfer approaches in transplant tolerance to achieve tolerance to some islet auto-antigens that are implicated in the pathogenesis of diabetes.

Sharland used this new-found knowledge to apply for seed funding from the Diabetes Australia Research Trust.

“Perhaps if I had received a Thompson fellowship two years earlier I wouldn’t have seen so much benefit as a result.

“It came just when I needed it and I was able to capitalise on the ideas and turn them into a funded project. It was very encouraging and the timing was just perfect.”