Betting Big On The Brain

Professor Nancy Ip blends the latest technologies with the ancient wisdom of traditional Chinese medicine, all in the name of solving challenges such as Alzheimer’s and other neurological disorders.

AsianScientist (Jan. 25, 2016) – For Professor Nancy Ip, dean of Science and director of the State Key Laboratory of Molecular Neuroscience at the Hong Kong University of Science and Technology, traditional Chinese medicine is a treasure chest of new compounds waiting to be discovered.

For years, she and her research group trawled the Chinese pharmacopeia, searching for new drugs to treat complex neurological disorders. Among their most promising leads to date is rhynchophylline, a compound extracted from the cat’s claw herb (Uncaria rhynchophylla) used to treat convulsions.

But Ip’s confidence in traditional Chinese medicine has not meant that she has shunned modern techniques. On the contrary, her lab makes full use of the latest technologies that science has to offer, from cutting-edge microscopy to optogenetics.

An academician of the Chinese Academy of Sciences and foreign associate of the National Academy of Sciences (USA), Ip has been recognized with numerous honors including the L’Oréal-UNESCO Award for Women in Science the National Order of Merit of the French government, and the National Natural Science Awards. She has also been honored by Asian Scientist Magazine on its inaugural Asian Scientist 100 list.

In this exclusive interview, Ip takes some time out of her busy schedule, and in between flights, to speak to Asian Scientist Magazine about her research.

What first made you interested in science?

For me, it was my high school biology class that got me really interested in learning about the various systems in the body. When I was an undergraduate, I did a chemistry final year project on organic synthesis. That experience was really transformative and sparked my interest in becoming a scientist.

So I applied to graduate school and became a student in the Department of Pharmacology at Harvard Medical School. In particular, I went into neuroscience because I realized that there is a lot that is unknown about the brain and I wanted to contribute to the field.

Could you tell us about the neurotrophic factors that you identified and why they are significant?

I worked on neurotrophic factors at Regeneron Pharmaceuticals, where I was a senior staff scientist. We identified novel neurotrophic factors and were the first to decipher the signaling mechanisms for these proteins which support the survival of neurons.

We demonstrated what happens when these factors bind to their receptors, what the underlying signaling mechanisms are, and the biological significance of growth factors. Our work revolutionized the field and had a very important impact on developing treatments for neurodegenerative diseases.

Regeneron conducted a number of clinical trials to develop neurotrophic factors for therapy, but encountered several challenges. For example, these factors cannot cross the blood brain barrier. There is still an ongoing effort to identify small molecules that can mimic the actions of neurotrophic factors, and I hope that some of these efforts will be successful one day.

What would you say has been your biggest research breakthrough so far?

It is very hard for me to pinpoint one breakthrough because I have had the opportunity to work on many different exciting projects throughout my career. In the early part of my career I worked on neurotrophic factors, to understand the molecular basis of their actions in our brains, and how they regulate neuronal survival and differentiation in normal and disease conditions.

After I returned to Hong Kong, I was interested in understanding the regulation of communication between brain cells, and strengthening and weakening of their activity—the so-called modulation of synaptic transmission and plasticity.

It is known that direct regulation of some of these pathways at the synapse may underlie the synaptic dysfunctions that we see during the progression of neurodegenerative diseases such as Alzheimer’s disease. Synaptic plasticity is also thought to be the underlying basis for learning and memory.

In Alzheimer’s disease, synaptic dysfunctions are observed at the early stages of the disease. If we have a better understanding of how they become deregulated, then we can find ways to intervene and maybe slow down the progression of the disease. This is the translational aspect of our work. If we can identify some compounds, for example from Chinese medicine, these can be further developed into therapeutic treatments.

Professor Nancy Ip with Chinese Academy of Science President Bai Chunli (left) in 2012. Credit: Nancy Ip.
Professor Nancy Ip with Chinese Academy of Science President Bai Chunli (left) in 2012. Credit: Nancy Ip.

In 2014 you identified a compound, rhynchophylline, which has been found to potentially treat Alzheimer’s disease in the laboratory. What is the status of the research on that compound at the moment?

In our animal models, rhynchophylline worked very well; it rescued the impairment in synaptic plasticity. We also have unpublished data that showed that rhynchophylline effectively restored performance of Alzheimer’s disease transgenic mice in the Morris water maze and other memory behavioral tests. I think the compound has potential. But drug development is a long process; just because a drug candidate works in animals does not mean that it will work in humans.

Right now, we are making derivatives by chemically modifying rhynchophylline, testing their efficacy and stability, and so on. We are also characterizing new derivatives in various animal models.

At the same time, we are trying to identify strategic partners, as we need expertise in drug development. In a university setting, it is very difficult for us to take the investigations further. Currently, the university is in discussions with interested parties to see if they are keen to develop the project further.

Do you think Professor Tu Youyou winning the 2015 Nobel Prize in Physiology or Medicine has any impact on science in China?

I certainly think so, especially because her work relates to Chinese medicine which has been used for thousands of years and is a very precious resource for drug discovery. This is also why we selected [traditional Chinese medicine] to be the source of our drug screening. We are also using advanced technology to modernize Chinese medicine for the global population, not just China.

Additionally, I do think that Professor Tu’s win will have a huge impact in inspiring young women to consider science as a career. Her achievements illustrate that persistence and hard work is gratifying and will be rewarded. We need more female role models, and she certainly is one of the best role models that we can find.

From your experience, what policy changes would make research a more viable career option for women?

It’s a step-by-step process and policy changes need to take place at different levels. At our university, we have a committee on family-friendly practices. I chaired that committee, developing policies to help our female faculty overcome certain challenges. For example, we provide support to them during their pregnancy and childbirth by reducing their teaching load and extending their tenure clock. We also have fellowships to help female PhD students and postdocs obtain research experience at prestigious labs overseas.

Another way to encourage women to stay in science is to recognize their achievements. The L’Oréal-UNESCO Award for Women in Science, which recognizes women scientists who have made significant contributions to their fields, is one example. I think it is very encouraging for young women scientists to see that their research successes will be recognized and rewarded.

It’s an exciting time to be in neuroscience, with innovative new techniques like optogenetics and intravital two-photon imaging and so on. In your opinion, what has been the most exciting development in the last five years?

Optogenetics is one of the most revolutionary advancements in recent years. It’s an immensely useful tool. It allows us to control the activity of a selected group of neurons in a well-defined manner, both spatially and temporally, and examine the consequences. In doing so, we can understand the functional role of these specific populations of neurons, how they control our brain functions, and what happens if we selectively activate them.

Could you tell us a bit more about your involvement in the China Brain Project?

I have been involved since the beginning. In 2013, a group of neuroscientists had a brainstorming session to determine how to promote neuroscience research in China, which resulted in a national strategic discussion and the development of the China Brain Project initiative.

Our aim is to combine basic and applied research to understand how the brain works under normal physiological and pathological conditions, and to develop brain-machine intelligence technologies. We also hope to come up with new approaches for the diagnosis and intervention of brain disorders.

Why has China made brain research such a big priority?

Brain research is not just a priority in China; it is a global priority. The US started their Brain Initiative, which was followed by the Human Brain Project by the European Union. Then there were other projects announced by countries like Japan and Korea.

It has been estimated that about 20 percent of China’s 1.3 billion people suffer from some kind of neurodegenerative or neuropsychiatric disorder. Just as an estimate, there are currently about eight to nine million who are afflicted by dementia in China. This number will increase by at least three-fold by 2050 if we don’t take immediate action. There is an urgent need for us to come up with better diagnoses and treatments, not just in China, but globally.

This article was first published in the print version of Asian Scientist Magazine, January 2016.


Photo: Nancy Ip.

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Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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