SHARE

AsianScientist (Nov. 18, 2015) – With their ability to develop into any of the specialized cells in the human body, stem cells have captured scientists’ imagination for their possibilities in regenerative medicine. While just four transcription factors are sufficient to reprogram adult cells into induced pluripotent stem cells (iPSC), what exactly happens to the network of over 2,000 transcriptional regulators remains poorly understand.

Professor Ng Huck Hui, the executive director of the GIS since 2011, aims to find out. His work focuses on using technologies such as RNA interference and chromatin immunoprecipitation to discover what makes stem cells tick.

His work has been recognized by awards such as Singapore’s National Science Award (2007), the Singapore Youth Award for Science and Technology (2010) as well as the President’s Science Award (2011). In addition to leading GIS, he serves as an editorial board member for journals such as Cell, Cell Stem Cell and Genes & Development.


What motivated you to study gene regulation in stem cells?

Gene regulation is about how genes control the property of stem cells. Our overarching motivation is, if we do not understand the internal operations of the cell, how can we manipulate them? In the long run, if we want to know how we can harness the full potential of stem cells, we must first study them and understand what are the processes that control the stem cell’s state and the processes that tell the stem cells to differentiate along this path and not the other path.

Our overarching goal is to eventually apply the knowledge that we learn from stem cell control in future clinical applications.

In terms of the most exciting topics in biomedical research, understanding the properties of stem cells is definitely one of them. This is because these cells have the ability to divide, to differentiate; I’m captivated by this very special property of stem cells.


What are some of the clinical implications of your work?

At GIS, we focus on genomics. We want to understand the basis of DNA, of inheritance, the function of genes. It all centers around nucleic acids.

In the long run, if we think about treating human diseases or conditions, in addition to drugs, we should explore the avenue of cell-based therapy. That means that maybe, perhaps in the future, we can put cells back that will replace the dysfunctional part of the body.

The second possibility is that perhaps we can think about reactivating some of the mechanisms of stem cells in the body without putting in the cell itself. It could be differentiation, cell renewal–these are some of the long-term implications for our current work, which is firstly to understand the molecular control of stem cells, then extrapolating into the future to try to harness the unique properties of stem cells and gain knowledge from that.

What is one thing GIS has achieved that you are most proud of?

It’s very hard to think about only one thing, because GIS has done a lot! I would put it in the context of three major themes:

1. The people: GIS is a magnet for scientific talent. We have managed to attract very good people with a passion for research.
2. The science: We are the center of discovery for genomics of different diseases. Over the past decade and more, we at GIS have discovered a wide variety of different genetic basis of different conditions.
3. The culture: GIS is an institute, it’s not a laboratory; it’s not a PI. We have formed a culture that promotes collaborations and working together.

What are the attributes that make GIS unique?

GIS is a technology-centric institute. That means that everyone has to work with someone who knows better in other disciplines. For example, for the projects that we work on, a single lab cannot do it alone. We have to work with other labs to execute a bigger project. That sort of culture is imprinted in the projects that we run, and that’s why we need to work in a very collaborative manner. In addition, not only are we working collaborative internally, we also work very closely with hospitals and the other tertiary institutions.

My vision is to develop GIS into one of the most influential institutes in genomics. We want to be the hotbed for scientific discovery and innovation.

The areas that we are focusing on will firstly be human genomics. If you think about understanding our genome, we have [come] a long way in terms of the technology and how much it tells us about the genetic basis of some diseases, as well as what exactly is our genetic makeup. But we are only at the beginning stage because future technology will allow us to have a wider coverage and a deeper view about our genomes. It will allow us to look at epigenetics for example. We will need to continue to apply next generation technologies in trying to understand the genetics and epigenetics of human diseases. This is the first pillar.

Also, because we have learnt so much about genetics, we also learnt about the variation between human beings. We want to be able to develop disease models that tell us how we can study human diseases in the laboratory. This is the second pillar, which is human disease modeling; we want to link genetic insight to functional insight.

At GIS, we have a spectrum of academic research: all the way to translational and commercialization. For basic research, it’s more about identifying the genetic basis of diseases. For translational research, it’ll be on developing and identifying biomarkers and seeing how they will improve diagnostics in the clinic. Additionally, developing disease models will help us to translate as well, because that enables us to do drug screening and try to understand how to develop better drugs.

Some of the more promising research would be projects that work on making the real cells. We all understand that stem cells can differentiate into specialized cell types. What we hope to achieve is that the specialized cell types will look like the real cells in the body. There’s no point in making a cell that is different from the body–what is the point of studying artificial cells?

The second important area is to create mini-organs. When we think about the human system, it is made up of multiple, different cell types. We must think of a way to put these different cell types together so they can function as a system. Another term for mini-organs would be organoids. I think this will be the most promising research field in the community. These will be the breakthroughs that will come from Singapore in the next few years.


What advice would you give to young scientists in Asia?

My advice to young scientists is: explore the science in Asia; many opportunities await [you]. At the same time, have a global outlook in science and technology.

We are in the era of the rise [of] Asia. You can see that many Asian countries have good GDP growth–they are building and expanding very fast. What is more important for young scientists is that many Asian countries are investing heavily in research. That means that many innovations will come from Asia.