Casting the net: open source drug discovery in China
Dr Li Chi Ho (Croucher Fellowship 2007 and Croucher Scholarship 2003) shares how research and development services company in China's utilises the wealth of knowledge in scientists from the globe to co-create innovative biotech research and pharmaceutical products.
Dr Li Chi Ho got his start in science through a childhood love of animals and the wealth of answers to be found in biology textbooks. “Fundamental biology still draws me in, but my questions grew bigger over time,” Ho remarks, “Applied biology, answering real needs of real people, depends as much on your knowledge of the basics as it does on technical skill; it’s a different kind of creativity.”
Ho followed this interest to the Chinese University of Hong Kong, attained a BSc and MPhil in Biology before going on to the University of Heidelberg as a Croucher PhD scholar in Molecular Cell Biology where he studied transcriptional regulation in parasites causing African sleeping sickness. In 2007, Ho won a postdoctoral position at Harvard Medical School as a Croucher fellow to continue his research on post- transcriptional regulation on RNA, DNA, and protein synthesis, with a focus on stress-induced granules which interfere with the transcriptional process.
As he planned a career after this postdoctoral fellowship, Ho found himself wanting something outside academia to really challenge himself and see what could be achieved using what he had learned. He made a fortuitous move to the bio-pharma industry just as the sector was seeing a resurgence. “It was an adjustment moving from pure research to more business-oriented science,” he says, “but I enjoy working with various kinds of people towards a targeted solution to a problem, and being involved with several projects at once.”
Now a Senior Director at WuXi AppTec’s biology department in Shanghai, China, Ho is at the centre of projects between research, biotechnological innovation, and the pharmaceutical industry. The company specialises in optimising research and development for smaller biotech companies, preparing products to meet industry standards. This includes research and manufacturing for small molecule, genomics, biologics, cell and gene therapy, medical and molecular device testing.
Ho heads WuXi’s Biologics department, which has a unique open source platform to encourage creative, collaborative approaches to healthcare, with more than 3,000 researchers currently registered.
The department itself coordinates projects, from idea conception to testing and commercialization, and is quickly becoming a leading pharmaceutical outsourcing leader. With the rising attractiveness of the Chinese market, both local and international companies try to find a foothold there. The diversity of projects thus is something Ho clearly relishes. He might be involved in more than ten projects at once ranging from cancer therapy to Lyme disease treatments.
Ho’s team integrates chemical and biological methods to design new compounds that meet preliminary targets in vitro and make modifications on structure and potency before clinical in vivo study.
The drug discovery process starts with high throughput screening of large compound ‘libraries’ of molecules and proteins against biological targets that are known to be disease modifying. The hits from these screens then inform further modification of the drug for optimizing effectiveness, side effects, stability, and bioavailability before moving on to testing in cells.
Along the way, Ho’s team works with academics, researchers, and other teams involved elsewhere in the drug’s journey to ensure that it is a new approach, safe, cost-effective, and answers a commercial or health need.
Ho is particularly keen on the small molecule drug discovery program, the process by which new candidate medications are found, dealing with key biological viability in the pre-clinical stage with a focus on in-vitro testing. This emerging method of targeted treatment seeks to revolutionise modern healthcare approaches, bending drugs to specific targets, blocking activity or changing biochemical functions.
Small molecules can go into any area of the body, even the blood brain barrier, and have a more stable molecular compound, though this comes with higher toxicity. They also tend to be chemical agents instead of larger molecular drugs to give a more obvious biological effect. Larger molecules can only bind to cell surface targets but have an advantage in specificity with lower side effects.
Doctors are advocating for more holistic pros and cons in treatment options, and researchers are racing to keep up. In cancer therapy, side effects of chemotherapy are lesser priorities to capturing rogue cells, whereas metabolic and diseases of age which require longer-term treatment, toxicity over time and side effects take precedent.
The ability to immerse himself in various biotech and pharmaceutical projects from start to finish has given Ho a first-row view into how the whole field is changing. “Biology is such an elastic tool, especially with the new technologies coming up. It also holds the answers for changing needs and health trends in our societies,” he says. “It’s interesting to see scientists as part of their communities, leading the way for smarter, safer healthcare.”
Dr Chiho Li obtained his BSc. and M.phil degree at the Chinese University of HongKong in 2003. He got his PhD degree from the University of Heidelberg in 2007. In 2009, after he finished the Postdoc training in Harvard Medical School, he started his career in the field of drug discovery in industries. Dr Li is currently a senior director of the biology department in WuXi AppTec Co. Ltd. and located in Shanghai. His duty is to lead biology team to support small molecule drug discovery programs.
To view Dr Li's Croucher profile, please click here.