October 2015 | Issue 20
Helping kidneys heal themselves
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By Nicole Lim
Assistant Director, Communications & External Relations

Human clones reared to become organ donors for their 'sponsors' are the focus of books such as Never Let Me Go and films such as The Island. But what if you could grow or help organs repair themselves without creating such murky dystopias?  

hat's exactly what Nanyang Assistant Professor Xia Yun hopes to achieve. With the number of people with end-stage kidney disease (often a consequence of many metabolic and cardiovascular conditions, including diabetes and high blood pressure) rising rapidly and treatment options limited to dialysis and transplant, Asst Prof Xia is making waves in the field of regenerative medicine with her pioneering work on deriving kidney-like cells from human pluripotent stem cells. The work, which she completed while working at the internationally renowned Salk Institute in California, USA, was the first of three papers which showed that it was possible to generate kidney-like cells from human induced pluripotent stem cells. In fact, these papers have paved the way for researchers to develop improved methods that enabled them to generate kidney progenitor cells that resemble the kidney cells of a first trimester human foetus.

Nanyang Assistant Professor Xia Yun

​Ass Prof Xia said, "Theoretically, this means we could grow whole replacement kidneys in a petri dish on demand. Although this most recent study, and others like it, has made significant advances in growing a kidney organoid from stem cells, we are still a long way off a fully functioning adult kidney. The more realistic goal remains to identify the window of opportunity when the kidneys start to get damaged and to encourage them to repair or regenerate the damaged or lost tissues. But of course, we're not giving up on the challenge to grow a whole organ for transplantation!"

Like any other organ in the body, the kidney is affected by the overall health of and age of the body. As we age and get sick, cells are damaged or destroyed, affecting the kidneys' ability to clear waste from the body. But some cells survive and acquire some properties, which make them resemble progenitors of an earlier development stage. After the damage is done, these survivor cells regrow into the lost cells, and can in some instances repair the damage. However, if the cells keep getting damaged or the damage is too great, they may not be able to complete this process.

"What we want to find out is when that window opens, how long it opens for and what other factors affect it. For example, is the window open if you have severe disease or is it affected by how old you are? Can we manipulate it and encourage the surviving cells to regenerate better?" said Asst Prof Xia.

To pinpoint the mechanisms that are involved in this intricate interplay, she works with induced pluripotent stem cells, a method first described by the Nobel laureate Professor Shinya Yamanaka, whose team succeeded in identifying a small number of genes in mice that when activated turn skin cells into embryonic-like stem cells, which has the potential to grow into any type of cell in the body

"This dramatically changed my field of vision. With induced pluripotent stem cells, we could grow neuron stem cells in two weeks, and beating cardiomyocytes in eight days! And induced pluripotent stem cells are much more accessible both technically and ethically comparing with embryonic stem cells, which scientists had to rely on before this seminal discovery."

It changed her horizon so much that she decided to embark on a whole new area of expertise after completing her PhD on cancer signalling pathways at the National University of Singapore. Looking for
opportunities to get involved in stem cell biology, Asst Prof Xia applied to institutes in the US, eventually accepting a position in Professor Juan Carlos Izpisua Belmonte's lab at the Salk Institute. The renowned developmental biologist offered her the opportunity to explore an area that was based on basic research, but had the potential to be translated into clinical applications.

"It was the perfect opportunity. Salk was just making its name in stem cell biology and he offered me an area where I could work on fundamental biological processes that are relevant to human health," said Asst Prof Xia.

ut after five years of working in the US, Asst Prof Xia, whose appointment at the School is the first in a series of new Nanyang Assistant Professor appointments, was keen to come back to Asia, where she feels more at home. Looking for opportunities, LKCMedicine's focus on translational research stood out for her. "The clear vision from the leadership, the stellar faculty and this focus on translational research were very attractive to me," said Asst Prof Xia.

"The fact that LKCMedicine and NTU are both young institutions also really appealed to me as I believe that the younger the institution the greater its potential. There's more room for manoeuvre, to innovate and introduce new practices," she added.

Barely two months into her appointment, Asst Prof Xia is already brimming with ideas for collaborations that can expand her work. She hopes to work with developmental biologists at LKCMedicine to get a better understanding of the entire development process of a kidney, something that stem cell biologists may overlook as they tend to focus on key milestones. She's also keen to explore areas of overlap with other faculty as well as clinicians from the School's healthcare partners.

Apart from her scientific contributions to the School, Asst Prof Xia also hopes to make her mark on the
School's culture by introducing a policy where researchers and scientists are encouraged to offer their help whether it is in terms of resources or expertise to each other.

"When I was revising my manuscript on generation kidney-like cells, I just sent a 'request for material' email around the Salk scientists to ask for a human cell line as control that the reviewers had asked for. Within days, I had the additional data using the cell offered by a colleague in another lab. In the end, this helped to get our paper published ahead of the other two groups."

​If you want to find out more about Asst Prof Xia's work, she will be giving an LKCMedicine Lecture on Wednesday, 28 October 2015 at 5pm at the Seminar Room, LKCMedicine Novena Campus, 11 Mandalay Road.