Advancing medicine, changing lives - Medical Research Council

PROFILE: Professor Roger Patient, MRC Molecular Haematology Unit, Oxford
Targeting
a healthy
heart and
circulation
Rates of heart disease and stroke are
climbing the world over, making it a priority
area for MRC funding. Our ground-breaking
research in cardiovascular disease and
stroke stretches from understanding
the genetics of heart conditions and
regenerative stem cell therapies to
encouraging behavioural change through
the use of mobile phone apps.
Every six minutes someone dies of a heart attack in the UK.
Heart attack is a frightening and debilitating condition that
can cause permanent damage to the heart in those who
survive it, drastically altering the patient’s health. But what if
there was a way to repair the heart and allow these patients
to lead a normal life again?
That is one of the many quests of Professor Roger Patient
at the MRC Molecular Haematology Unit (MHU) in Oxford,
who is investigating the possibility of using stem cell
therapy to regenerate damaged heart muscle.
Roger started his scientific career as a chemist, but soon
decided that DNA was by far the most interesting chemical
he’d studied and made the leap to genetics. At that time,
the first experiments to transfer animal genes into bacterial
cells were taking place, and Roger recalls being accosted by
news reporters on his way into work who wanted to know if
he was making a ‘test tube monster’.
Later he shifted gear again into developmental genetics
after making the seminal discovery that embryonic and
adult red blood cells are descended from entirely different
cell lineages. It’s in this field that he’s worked for the past 20
years, researching how the blood and cardiovascular system
forms in the developing embryo.
But these days, as a senior scientist at the MHU, Roger is
more likely to be found grappling with research problems
than pipettes.
“I became a lab head because for me, the exciting thing
about research is the concepts and ideas. Although I loved
doing the experiments, I consciously dropped being handson
to make the lab bigger and to broaden the reach of what
we were able to do,” explains Roger.
And his lab’s remit is certainly broad. Unravelling the
intricacies of how cells, genes and molecules come
together in the embryo to make blood, veins and heart can
teach us about congenital heart defects, blood cancers and
even how to repair damage inflicted by a heart attack.
In 2011, Roger’s group published research they’d carried
out in zebrafish – a creature with an incredible ability to
regenerate its heart muscle, even as an adult.
But what’s the relevance for human health?
“Our bodies are able to regenerate tissues like liver and
skeletal muscle when they are damaged, but we can’t
regenerate cardiac muscle. So if this muscle is damaged
through heart attack, where there’s a blocked artery, we
never get the use of it back. Further heart attacks will lead
to heart failure because there’s no healthy muscle left,”
Roger explains.
“So if we can we can manipulate these heart stem cells in
fish embryos to make new tissue, in the longer term we can
look to try and do the same in human hearts – even adult
hearts – if we can identify the equivalent cells in people.”
Repairing the heart would not only require regeneration of
the muscle but also the vessels that supply it with blood.
So if the same population of cells exist in human beings as
Roger’s group has found in zebrafish, it might be possible
to manipulate them to regenerate both types of tissue,
perhaps by giving drugs which mimic the signals that tell
cells to turn into one type or the other.
The research also gives fascinating insights into how our
large, four-chambered hearts have evolved over millions
of years from the simple, two-chambered fish heart. Roger
and his team think the population of cells they’ve found
in zebrafish were diverted as we evolved in order to make
more heart muscle to increase the organ’s size.
“Our hope is that, in humans, if these cells were recruited
into the muscle-making population of cells in recent
evolutionary history they may have retained a ‘memory’ of
making the cells of veins and arteries,” explains Roger.
Regenerative medicine brings to mind science fiction images
of pulsating hearts growing in Petri dishes, but Roger thinks
the answer will lie in stimulating the body to repair itself
from within rather than transplanting tissue grown in the lab.
“If you transplant tissue into a heart, the cells have got
to organise themselves. And with a three-dimensional
structure like a heart that’s going to be very difficult. So
my thought is that they will be more likely to organise
themselves if they’re growing in situ than if they are
dropped in from the outside.”
The research showed that a protein called Fibroblast growth
factor (Fgf) can influence whether developing heart stem
cells become either new heart muscle or new blood vessels.
By manipulating levels of the Fgf protein in zebrafish
embryos and causing it to switch various genes on and off,
Roger’s group was able to control how many of each cell
type was made.
It’s early days for this research, and for now the search
continues for this elusive population of cells in people. But
Roger’s still hopeful that we might have an idea of how to
regenerate human heart tissue within five to ten years.
“It used to be that people like me working on basic research
would feel a long way from research going to the clinic, but
nowadays we don’t feel so far away,” he says.
32 | MRC Annual Review 2011/12 MRC Annual Review 2011/12 | 33