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Sheng Ding is a restless change maker. Trained at the California Institute of Technology and Scripps Research Institute, he’s a pioneer in manipulating stem cells with small molecules. He’s also wielded gene-editing tools to reprogram cells and founded companies to tackle diseases like cancer and heart failure. In 2016, Ding moved from the US back to Beijing, the city he grew up in, to make more contributions to science, he says.
There, he became dean of the School of Pharmaceutical Sciences (SPS) at Tsinghua University, where he continues to conduct stem cell research. He’s raised the school’s international profile by initiating joint PhD programs with US research institutes and installing an advisory board dotted with big names, including pharmaceutical CEOs and venture capital gurus. Ding is also the director of the Global Health Drug Discovery Institute (GHDDI), the first nonprofit research organization in China funded through a public-private partnership. GHDDI draws its support from the Bill and Melinda Gates Foundation, Tsinghua University, and the Beijing municipal government.
To help in the fight against the current coronavirus pandemic, GHDDI is sharing its compound libraries, its artificial intelligence platforms, and its drug discovery expertise with the international community. C&EN talked with Ding about GHDDI’s role in this fight and his hopes for the future in China.
▸ Hometown: Beijing
▸ Education: BS, chemistry, California Institute of Technology; PhD, chemistry, Scripps Research Institute
▸ Titles: Director, Global Health Drug Discovery Institute; dean, School of Pharmaceutical Sciences, Tsinghua University; senior investigator, Gladstone Institute of Cardiovascular Disease; professor, University of California, San Francisco
▸ Most recent companies he cofounded: Nayan Therapeutics (2018) for treating retinitis pigmentosa (loss of cells in the retina); Apros Therapeutics (2016) for treating hepatitis B and cancer; Tenaya Therapeutics (2016) for treating heart failure
▸ Hobbies: I love to travel, even though I no longer have much time. I’ve especially been interested in exploring UNESCO World Heritage Sites. I’ve been to over 200 of those.
▸ Favorite small molecule: I like aspirin—such a wonder drug.
GHDDI aims to develop drugs for diseases that disproportionately affect the developing world. Tell me about one of these diseases and the successes the institute has had in this particular area.
Echinococcosis affects more than 1 million people worldwide, and it’s prevalent in areas where people raise grazing animals for a living. Echinococcus is the parasite (a tapeworm) that causes the disease. It lives in sheep. When a person eats infected lamb, the parasite’s larvae can get into the human body and grow cysts on the person’s liver. Besides surgery to the liver, the only treatment available is a chemotherapy drug. In addition to the chemotherapy being toxic to the liver, it’s not very efficacious at killing the parasite.
To find a better drug, GHDDI screened more than 12,000 compounds that have gone through Phase I safety studies in humans. These compounds belong to GHDDI’s drug-repurposing library called ReFRAME, which was funded by the Gates Foundation. It’s the largest of its kind in the world.
Based on the screening results, we selected compounds that killed the parasitic larvae while not being toxic to human cells. We’re currently doing experiments with parasite-infected rodents. After this, we aim to select one or two compounds for clinical studies by the end of the year.
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In your lab at Tsinghua University, you do research on stem cells. But you are also the director of GHDDI, which focuses on global health. How do you reconcile these two roles?
My research interests have always been in stem cell research and translating discoveries in this area into treating various diseases.
The drugs we develop at GHDDI are mainly for infectious diseases. Although I didn’t previously have much expertise or knowledge in this domain, I picked those up relatively easily, at least at the high level. Moreover, the logic of drug discovery remains the same: as a researcher (and entrepreneur), I’ve carried therapeutic candidates into clinical studies for treating cancer, tissue degeneration, and cardiovascular diseases. That experience has been helpful for my work at GHDDI to do drug discovery in global health.
And here’s another way my previous experiences could benefit GHDDI’s future work. Last October, the US National Institutes of Health and the Gates Foundation announced that they will each commit $100 million to develop affordable gene-editing approaches for HIV and sickle cell disease. Gene editing was unheard of in global health before—it doesn’t fit the traditional thinking that we should use cheap and convenient approaches in developing countries. But the field is now considering this a disruptive technology, and it could fundamentally change how people treat and cure global health diseases.
You became director of GHDDI in 2016, when it was founded. What’s your vision for the institute?
First, we need to deliver first-in-class drug candidates for global health diseases into clinical studies. Now in our third year, we have secured infrastructure and people, as well as a balanced pipeline of programs tackling different diseases at different stages. Given time, drug candidates will be delivered.
We also have to develop specialties, or competitive edges, in certain areas of disease biology and in certain drug discovery technologies. That’s my second goal for GHDDI. Once we have those specialties, GHDDI can disseminate its ideas, technologies, and talents to new places. For example, we have an infectious disease program to target host immunity (treatments that activate a person’s innate immune system to go after pathogens). Such therapeutics can be repurposed against cancer. By disseminating these innovations, we would be able to maximize their impact and, at the same time, get financial returns through means like licensing and spin-off companies to sustain our own growth.
Has your vision changed during the COVID-19 pandemic?
As the novel coronavirus strikes the whole world, I think institutes like GHDDI should also take on some advocacy work for global health and public health diseases. Researchers working in the field have always known that government and industry investment is limited for these diseases, especially in translational development.
In the past, people usually just talked about this limited investment, without much action, because they never saw any significant impact. This time, the impact is very significant. In fact, the economic loss is so massive that hundreds and thousands of drugs could have been developed with the lost money.
Through our partnership with high-profile organizations like the Gates Foundation, we could communicate with government agencies, industry, and the general public so that they’d learn more about why it’s important to invest beforehand and be more prepared when similar diseases hit again. There is a long way to go. And we’ll have to spend many years to make changes happen.
How is GHDDI responding to the current coronavirus pandemic?
One example of how we’re responding is that GHDDI’s artificial intelligence team and its researchers built a portal on GitHub called Targeting COVID-19 to share our drug discovery activities with the international community. The information includes key literature on the virus, SARS-CoV-2, and relatives like SARS-CoV and MERS-CoV; our computational modeling and assay results; and internal data mined from various sources.
We developed the portal to avoid redundant efforts and to provide necessary support to investigators with certain drug discovery expertise but not the capacity to carry out the full process. With this portal, we could help to sustain these investigators’ efforts till they reach certain critical points for translation.
GHDDI has also built an Alibaba cloud-based AI platform to help researchers screen for molecules against COVID-19. The platform provides substantial high-end computational capacities to global researchers on anticoronavirus research, allowing them to run drug discovery applications such as our AI-based modeling process. We are sharing our ReFRAME drug-repurposing library with researchers too.
What’s your biggest goal in the next decade? You’ve founded biotech companies in the US. Will you start new ones in China?
Not in the next few years. Tsinghua SPS and GHDDI are still in a growth stage, so I’d like to spend more time and effort there. Starting a company is something I’m familiar with, and it’s relatively straightforward. As long as you have good research and real impact, further translation will naturally happen. So my biggest goal is, again, encouraging more organizations to replicate the activities we are doing at GHDDI and at Tsinghua SPS. It’s not that I’m not going to focus on my own research or translational work. But I’d like to set my main goal at achieving something I haven’t done before. With more people following GHDDI and Tsinghua’s lead, those activities will become more useful for the whole world.
Cici Zhang is a freelance science writer based in China.
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