Profile: Roger Patient
Could research into the extraordinary regenerative properties of the zebrafish heart one day help people who’ve had heart attacks? In an article taken from our Annual Review 2011/12, Sarah Harrop speaks to Roger Patient from the MRC Molecular Haematology Unit to find out.
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 hands on 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. 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.
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.”
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.
Download the MRC Annual Review 2011/12: Advancing medicine, changing lives, available in pdf or ebook formats.