About me
I am a specialist registrar in surgery, training to be a transplant consultant. Alongside my clinical work I have also undertaken a PhD in basic science: I split my time between the wards and the laboratory where I work on a problem called ischaemia reperfusion injury (see the explanation below). I chose transplantation because of the astonishing difference it makes to patients' lives- the average life expectancy after a liver transplant is 22 years yet without a graft many patients would not survive for a year. Alas too many people who might benefit from a liver transplant never get this chance because of the shortage of donors. It is this which motivates my research efforts and also my contribution to the BTS as the public engagement committee chairman.
Outside of work I have a busy family life with three young children: when I get the chance I love to listen to music. Every year I promise myself I'll learn to play the piano again but it's yet to happen...
The clinical problem
The rate of liver failure
is increasing rapidly in the UK: liver transplantation is often its
only definitive treatment. Liver Transplantation requires a liver to be
taken from a deceased donor, transported on ice, and reimplanted in a
recipient. During this time, the blood supply to the organ is
interrupted, thus depriving liver cells of oxygen, an injury termed ischaemia. When the blood supply is reconnected in the recipient, a further injury occurs, termed reperfusion injury. Ischaemia reperfusion injury
can cause the transplanted organ to fail, often resulting in the death
of the recipient. In some donor organs the risk of ischaemia
reperfusion injury is greater: when surgeons judge the risk to be
excessive, those organs may be discarded, worsening the donor crisis.
We have previously shown that overcoming ischaemia reperfusion injury
could increase the supply of donor organs by as much as 10% (Devey et
al 2007).
Our research
Ischaemia reperfusion injury
occurs in two phases. Initially, liver cells are injured by a lack of
oxygen. Subsequently the immune system is activated, which makes the
injury considerably worse. Embedded within the liver itself are immune
cells called Kupffer cells, and circulating in the blood there are
other immune cells which may be attracted to the liver after injury. An
important group of circulating immune cells are T cells. All T cells
are not created equal- they may be aggressive- causing very severe
injury (these are called Th17 cells), while others are benign and
reduce inflammation (these are called Treg cells).
We
believe that Kupffer cells coordinate the response of T cells to the
injured liver. Rather like the conductor of an orchestra bringing in
different groups of instruments to create a desired sound, we believe
that Kupffer cells are able to attract different populations of benign
or aggressive T cells when the liver blood supply is reinstated in the
transplanted liver. We have previously shown that a molecule called
HO-1 can operate as a “switch” on Kupffer cell behaviour. If we “turn
on” HO-1, Kupffer cells become much more benign: conversely Kupffer
cells become more aggressive if HO-1 is “turned off” (Devey et al
2009). We believe that using HO-1 as a “molecular switch” it may be
possible to make Kupffer cells attract more benign T cells into the
liver, and thus reduce injury.
If we are correct
that Kupffer cell “switches” alter the populations of T cells which
enter the liver following injury then we will have more completely
understood the biology of ischaemia reperfusion injury, and will be
better placed to develop novel therapies with which to improve the
outcome of transplantation.
