In their breakthrough study, Liu and his team found that the deletion of a gene called PTEN from laboratory mice with chronic spinal injuries activated mTOR, another gene. mTOR drove damaged axons to regenerate, and re-form connections, even when the treatment was initiated at one year after injury. Although more research needs to be done before human trials, the findings are highly encouraging, and considerably extend the window of opportunity for regenerating axons severed in spinal cord injuries. It’s a big step forward, as axon regeneration is a rare phenomenon that is difficult to facilitate.

Liu knew his discovery was a big step forward, but it would be difficult to inhibit PTEN without increasing pathological risk, because it is a tumor suppressor. But the professor knew that difficulties always present new opportunities, and success depends on perseverance and tenacity. He kept working on the problem, and just eight months later, came up with a solution.  

“We have explored alternative methodologies to activate mTOR which do not remove the PTEN gene,” says Liu. “The axons can be regenerated without getting rid of the tumor suppressor, so that risks can be highly reduced.”

Liu’s research team, which comprises eight scientists, including postdoc, MPhil, and PhD students, found that axon regeneration can be achieved through either optical or chemical stimulation of neuronal activity. The findings were published in Proceedings of the National Academy of Sciences, the official journal of the National Academy of Sciences of the United States of America, in February 2016.

In the optogenetic approach, it was found that overexpression of melanopsin, a light-sensing protein molecule found in the retinas of mice, could enhance the neuronal firing of retinal ganglion cells, and promote the regeneration of axons after optical nerve crush by activating mTOR signaling.

In the chemogenetic approach, it was found that overexpression of “Designer Receptor Exclusively Activated by Designer Drugs” (DREADD), a method which is is widely used as a tool to enhance neuronal activity, was able to activate Gq signaling at the downstream of melanopsin, which in turn activate mTOR signaling.

The new findings suggest that there are other ways to boost neuronal activities, and in turn, promote axon regeneration. “There is new hope that we will be able to facilitate neural repair. But there is still a long way to go, and more theories will have to be put into practice before these methods can be applied to human beings,” says Liu. So far, notes Liu, the regeneration has only taken place in the eye. “The next step is to look into the possibility of using similar strategies to promote axon regeneration in the spinal cord, which is a much more challenging model than the eye,” he says.

But one thing is for sure – Liu will never give up.  Liu has stuck to researching neural repair through thick and thin. “My main interest is venturing into the unknown and making discoveries,” he says. “I’m especially interested in discoveries that may offer hope to millions of people with long-term injuries.”

Prof Liu received his Bachelor’s degree from Peking University in 1998, and his PhD in neuroscience from Rutgers University, in the US. He worked at the Boston Children’s Hospital of the Harvard Medical School before joining HKUST in 2011. He says he encountered many difficulties and frustrations during the course of his research, but was inspired to keep going by his research supervisors, Drs Wise Young and Zhigang He.  “There were six or seven years during which I was getting nowhere,” says Liu. “I would have really given up without their encouragement.”

After joining Dr. Zhigang He’s lab at Harvard, Liu explored the problem using mouse genetics. In 2007, by collaborating with people in He’s lab, he and others found PTEN deletion could promote robust axon regeneration after acute injuries. A series of experiments and investigations have been carried out since then.

Liu advises his students to choose their research topics based on their real interests, and encourages them to face challenges in a positive way. He stresses that it’s very important to enjoy doing the research. “We owe a lot of our findings to the support of HKUST and Hong Kong Spinal Cord Injury Foundation,” says Liu. “The campus has a culture of respect, and a positive atmosphere. Professors mix freely with students, and never put on airs and graces. The university and foundation have provided continuous funding support over the past years.” His research team has excellent teamwork skills, Liu notes.

Hard work and passion are necessary for success in science, Liu says: “Once you identify your real interest in life, you will find the passion to chase it. The more challenging it is, the harder you have to work. If we quit at halfway through, all the efforts we have made will be wasted. The only thing to do is march forward.”

“As long as we are persistent, we will continue to grow. But we can’t choose the day or the time when we will bloom. That just happens when it happens. Remember that successful action is cumulative in its results,” he adds.

Liu has shown us that Rome was not built in a day.  We must have faith in ourselves and keep moving forward to achieve our goals.