Dr. Yingfu Li holds a Canada Research Chair in Nucleic Acids Research. He is a professor in the Faculty of Health Science’s Department of Biochemistry and Biomedical Sciences at McMaster University and a joint member in the Chemistry department. Li’s main area of research involves examining unusual functions of nucleic acids. When Yingfu Li was a little boy, he loved breaking and making things. Today, his curiosity has much higher stakes. Li, who runs the Yingfu Li Lab at McMaster University, examines how nucleic acids function and how they can be used as novel molecular tools for therapeutics, biomolecular detection, drug discovery and nanotechnology. “When DNA’s cousin, RNA, was discovered to function as an enzyme, it changed the notion of what DNA and RNA can do,” explains Li. “Part of what we do at my lab is apply that idea and use DNA for something nature didn’t intend it for — namely therapeutic applications. To do that, we create our own DNA-based enzymes (DNAzymes) and receptors (DNA aptamers) because there is no natural source to fetch the DNA or RNA molecules for this purpose.”
Far-Reaching Impact. These therapeutic applications are crucial in numerous areas. For example, microbial pathogens (such as E. coli) pose serious threats to public health and safety, and labourious and expensive pathogen tests can hinder effective frontline preventative care. But Li and his team are using their DNA-based molecules to create a simple and inexpensive litmus test for bacterial detection. The same concept is being applied to creating non-invasive colorectal cancer diagnostics and neurodegenerative disease testing. “We focus on diseases to which we can apply collaborations,” says Li. “Research is complicated, especially in commercialization, so by combining different expertise we can be much more successful. In fact, in my colorectal cancer work, I work with gastroenterologist Dr. Bruno Salena. My interactions with him have really expanded my research to the clinical arena.”
Li’s efforts have also led to collaborations with several Canadian biotech companies and backing from organizations such as the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Weston Brain Institute. Most recently, Li has also set up his own biotech company, InnovoGENE, to commercialize his research group’s technologies. The challenges of years of grant writing and launching his company have, at times, been trying, says Li. But it is from these experiences that he offers advice to aspiring researchers considering commercializing their discoveries.
“You need to have a great team,” he says. “Trust your people and find collaborators who are willing to learn your language and whose language you are willing to learn. Also, nothing will be perfect. I see people giving up during less than ideal scenarios. You lose grants, for example, but it should make you think more strategically about what you need to do better. Commit to the process.”
Dedication and Drive. Commitment and collaboration are themes that appear throughout Li’s career. In fact, the latter drew him to McMaster in 1999. After receiving Bachelor’s and Master’s degrees in his native China, Li enrolled at Simon Fraser University in Vancouver. From there, he obtained his PhD and travelled to the U.S. for postdoctoral training at Yale. Several universities then courted Li.
“At McMaster, I was really impressed with the culture of collaboration, so I was convinced it offered the ideal setup to conduct collaborative research,” says Li. “Trying to advance this field and get people to think about DNA in a different way is what makes me feel most satisfied. Through interaction with industry partners, we not only push the field forward but combine scientific discovery with the potential benefit to society."
Since an early age, Heather Sheardown has been intrigued by the intersection between medicine and engineering for, as she explains, “the body is essentially a series of engineering systems.” After completing doctoral research on corneal wound healing, she continues to use her expertise in chemical engineering and biomaterials to address the widespread and serious issue of vision impairment and loss. For example, it’s been estimated that just two age-related ocular diseases, macular degeneration and glaucoma, affect about six million Canadians. As the population ages, the number of affected Canadians and associated healthcare and societal costs will only increase unless new and more effective approaches are found and commercialized. Founding director of the National Sciences and Engineering Research Council (NSERC) 20/20 Ophthalmic Materials Research Network, Heather is currently juggling responsibilities as the Canada Research Chair in Ophthalmic Biomaterials and Drug Delivery Systems at McMaster, educator, and founder of a biologic start-up, 20/20 OptimEyes.
What inspired you to expand from the ivy tower of academia to entrepreneurship? In my research, I was always thinking of the end user, of taking products from the lab to patients. Part of the reason I chose to come to McMaster was because the medical school is open to working with other faculties.
What problem is addressed by 20/20 OptimEyes? The eye is designed to protect itself. Current eye drops are not very good at delivering medicine to the target tissue because they have to penetrate a layer of tears as well as an inner layer of mucous, the mucin. We’re developing a new drug delivery medium that binds to the mucin so it can hold the medication in place longer. With this approach, you can reduce dosing frequency and improve clinical efficacy through controlled release.
What sort of applications are you planning for 20/20 OptimEyes? Our current focus is largely on the treatment of dry eye disease. Dry eye syndrome can occur at any age and can lead to inflammation, light sensitivity and even deterioration of eyesight. It’s a significant challenge for a lot of people. But once it’s developed, the technology can be applied to other conditions. Our recent grant from the Ontario Ministry of Research, Innovation and Science, for example, is looking at the potential to use this technology in the treatment of macular degeneration and glaucoma.
What’s your current objective for 20/20 OptimEyes? Our current focus is on conducting the sort of clinical research needed to provide evidence for the safety and efficacy of the technology and obtain approval from key bodies such as Health Canada and the FDA (Federal Drug Administration) in the U.S. Having these approvals will help to reduce the risk for companies who we hope will license our technology. Right now, we’re developing the pre-clinical package and we hope to have clinical trials with humans launched by as early as 2019.
What has helped you in moving from researching a good idea to developing a commercially-viable product? I’m very involved and benefiting from McMaster’s start-up incubators – The Forge and McMaster Innovation Park. But I’m also fortunate in that I can draw upon industry contacts and mentors that I’ve developed over the years. As well, as mentioned, this year we received government funding that made it possible to bring together nine industry partners and academic colleague from the University of Waterloo to start thinking about next steps and identifying the next generation of ophthalmic materials and drug delivery devices.
Any advice for students or researchers considering entrepreneurship? Entrepreneurship or working to commercialize something wouldn’t have been an option for academics ten or fifteen years ago. But I really encourage my colleagues and students to try it. Once you get the bug you don’t want to stop because you learn so much. Entrepreneurship is already changing academia. And we need entrepreneurs to improve care for patients and to help build the Canadian economy.
Dr. Sheila Singh, BSc, MD, PhD, FRCS(C), FAANS, is Head of Pediatric Neurosurgery and an investigator at the Stem Cell and Cancer Research Institute at McMaster University. A neurosurgeon who specialized in pediatric brain tumours, she is currently utilizing developments stemming from a Terry Fox Foundation grant to launch Empirica Therapeutics to commercialize new, precision-medicine treatments.
What sort of cancer do you research? There are currently three research programs in my lab focusing on some of the most aggressive and treatment-refractory forms of brain cancer: one on adult glioblastoma (GBM), another on pediatric medulloblastoma, and the third on secondary tumours that metastasize to the brain. Many people have heard about GBM because of some of the public figures it’s affected, such as Gord Downey, Ted Kennedy and John McCain. It’s a particularly deadly form of cancer because we can treat it with chemotherapy and radiation but in every case the patient relapses with a recurrent tumour that is even worse and nothing like the primary or original tumour.
How do you conduct your research? I was fortunate to obtain, with my partners Sachdev Sidhu and Jason Moffat of the Donnelly Centre for Cellular and Biomolecular Research in Toronto, a program project grant from the Terry Fox Research Institute (TFRI). This program is based on the theory that if you fund teams of researchers the whole will be greater than the sum of the parts. It’s a great philosophy because it enables teams of multidisciplinary cancer researchers to tackle a difficult problem using different biotechnological approaches. For our grant, we combine the labs of myself, a cancer biologist and clinician, Sachdev, an antibody engineer, and Jason, a functional genomics expert. If you were to draw a Venn diagram of our research areas, it would seem like our circles wouldn’t overlap but in reality they are complementary. Our collaboration made it possible for us to build a translational pipeline to quickly translate basic discoveries in the lab to treatments for patients.
What’s your current clinical target? We decided that instead of treating the primary tumour in GBM, we’re going to use our genomic technologies to find novel therapeutic targets for the recurrent tumour. The work starts with Jason’s genomic studies that enable us to discover and validate new targets on the cells of GBM tumours. Next, the team led by Dev Sidhu engineers new immunotherapeutic approaches against these targets. I’m the lead for the third phase, in which we implant patient tumour cells into the brains of mice, treat the primary glioblastoma with chemotherapy and radiation, and then test our new immunotherapies on the recurrent tumour. It’s an exciting program because we end up with novel targets and new therapies ready for human trials and commercialization.
What company are you establishing? Empirica Therapeutics applies a data-driven precision-medicine approach to brain cancer therapy. At this point, we’ve developed two ways of using the CD133 antigen target we’ve identified on recurrent GBM tumours through our TFRI-funded research: CAR (Chimeric Antibody Receptor) T-cells (an approach that is already being used for the treatment of some forms of leukemia and lymphoma) and BiTEs (bi-specific T-Cell engagers). To make our CAR T-cell therapy, you take some T-cells from a patient, genetically modify them to bind to the CD133 antigen expressed on tumour cells, and then put them back in the patient. The genetically-modified T-cells act like homing missiles, going straight to the cancer cells and destroying them. The other approach uses a BiTE, a bioengineered antibody with two arms: one attaches to our CD133 antigen and the other to a receptor found on T-cells. When you release our BiTEs into a tumour environment they bind to the CD133 antigens on the tumour cells and then snare and pull in T-cells to kill the cancer cell. It’s a really cool approach.
Why did you make the leap from academia to commercialization? I’ve been very happy in the worlds of academia, my lab and my patients and good at mentoring people who want to follow a similar career track and become a professor or neurosurgeon. But academia alone can’t cure brain cancer: we need to work with industry to tackle this complex problem. As well, research trainees are aware that tenured academic positions are rare today. There’s a whole new career track for scientists – particularly those trained to a high level of scientific competence – in industry. Setting up Empirica Therapeutics enabled me to branch out, develop colleagues in industry, and learn how to mentor trainees who will go on to work in industry or start their own companies.
What have been your biggest advantage and challenge in commercializing your research? Without doubt, my biggest advantage is being both a clinician and a scientist: industry loves this mix of skills. My biggest challenge was having no knowledge about the business side of commercialization. It’s a whole different language to me and there’s a really steep learning curve. I’m hoping that through my experience in launching this company we can develop new resources for the McMaster Industry Liaison Office for others who also have ideas to commercialize.
Any advice for potential entrepreneurs? You need to know your market but also your science. When commercializing science, your single strongest asset is the depth of your scientific knowledge. There’s a misperception that in industry your science doesn’t have to be a strong as someone working in academia, that maybe business or social skills are more important. But industry is becoming increasingly competitive and you need to be scientifically as strong as possible if you want to succeed.
A professor in the Department of Chemistry and Chemical Biology at McMaster University, Dr. John Valliant is internationally recognized for his research in radiochemistry and creating new diagnostic and therapeutic drugs (radiopharmaceuticals) for imaging and treating cancer. His work in developing and advancing new radiopharmaceuticals, improving patient care and generating economic growth has already earned him a number of distinctions, including being named one of ͞Canada’s Top 40 Under 40͟and, as part of a Canadian team of researchers, the Brockhouse Prize for Interdisciplinary Research in Science and Engineering. John is the founder of the Centre for Probe Development and Commercialization (CPDC) at McMaster; a not-for-profit centre of excellence established in 2008 to provide the necessary combination of scientific, technical, regulatory and business expertise. CPDC facilitates the translation of new radiopharmaceuticals into clinical tools to ensure patient access and the commercialization of Canadian discoveries. To date, CPDC has completed over 50 radiopharmaceutical discovery, development and manufacturing programs and brought over a dozen radiopharmaceuticals into clinical development. Dr. Valliant’s program has provided doses for thousands of patients and created two new companies, including Fusion Pharmaceuticals Inc. which is developing a novel treatment for chemotherapy-resistant cancers.
How did you come to work in work in the field of medical isotopes? I’ve always been interested in finding ways to exploit the science that I do to solve current healthcare challenges and in some way help people. When I came to McMaster, the University already had a longstanding tradition of working on medical isotopes. I focused on using the unique infrastructure in Hamilton and combining it with a research program in chemistry to develop the means to create new radiopharmaceuticals. People may be familiar with medical isotopes which are used daily for imaging tests (PET or SPECT scans). The power of our technology lies in its ability to look at the biological changes associated with disease rather than simply the structure of the disease. Radiopharmaceuticals allow for early detection and they can be used to guide treatment options. Theyare used extensively for the treatment of cancer but also have the potential to treat a wide range of other diseases, such as rheumatoid arthritis.
How did you become involved in commercializing your research? I have had the great fortune throughout my time in school and during my professional career to work with people that engaged in commercialization. For instance, the team I worked with during my post-doctoral fellowship developed Cardiolite®, an agent that is used in cardiac stress tests. As a Professor, I got to collaborate with emerging and innovative companies such as Molecular Insight Pharmaceuticals. These experiences, which were further broadened through my work at the CPDC, gave me unique insight into what it takes to successfully commercialize technologies – as well as the benefits to society from making the efforts to advance new technologies to market.
Who helped or encouraged you and your team to pursue commercialization? The Ontario Institute for Cancer Research (OICR) was a key supporter, as well as the Department of Nuclear Medicine, in Hamilton, largely because they were interested in seeing things move out of the lab and into the clinic. The OICR also had significant expertise in commercialization that helped cultivate the opportunity. While the desire to commercialize was there, we didn’t initially have the facilities or expertise to make it happen. The OICR encouraged me to apply to a federal program that was designed to promote commercialization – the CECR program. That was the start of the CPDC and my involvement in commercialization.
How does someone trained as a researcher make the leap to starting a commercial venture? A universal skill of any scientist is the ability to learn new things. If you want to start a commercial venture, you can apply the same skills used to be a successful researcher. You also need to surround yourself with experienced people who know commercialization. One thing I learned is that the amount of energy, drive and creativity needed to build a research program is similar to what is needed for engaging in commercialization.
How do you find the time to do all this when you’re wearing three or four hats -- researcher, educator, executive, administrator? Time is the number one challenge. It’s interesting to look back because at the time all this was happening my wife and I welcomed twins to the family. With three kids in diapers, it was certainly an exciting stage of our lives. I was fortunate that at that point -- when the opportunity to create the CPDC and focus on commercialization came -- my research group was established, I had great students, and the university provided me with some extra time to launch the CPDC. Continuous improvements to time management strategies and surrounding myself with talented people I could trust were ultimately keys to being able to wear multiple hats.
What has been your biggest advantage? I think it’s changing trends on two fronts. In my field there has been a lot of interest in the clinical use and commercialization of radiopharmaceuticals, which created momentum. There is also a changing culture at the university and in society. Stakeholders are now encouraging research translation and commercialization. It’s very different from when I started in academia, when commercialization was de-emphasized; you could do it but it really wasn’t regarded as an important contribution.
What’s next for your company? Fusion Pharmaceuticals will be starting a clinical trial on our lead agent this year. My goals are to have our technology help patients and create a highly successful pharmaceutical company here in Hamilton that will attract more investors, people and companies. I’d like to catalyze growth similar in innovation, similar to happened in Boston and San Francisco. We train fantastic students at McMaster. Many would love to stay in southern Ontario and raise their families here but to do so they need jobs in line with their education.
Do you have any advice to potential medical/scientific entrepreneurs? Take the risk. Entrepreneurship is about the willingness to take chances and not be afraid to fail. My experience has been that opportunities will come up at the worst possible time and can be a bit scary for people who spent most of their career in academia. Commercialization opportunities are rarely aligned with your professional or personal life goals or status – but you still have to willing to recognize and react to opportunities. There will be ups and downs but it is a truly enjoyable ride. I couldn’t have done it without the support of many advisors and colleagues and of course my wife and kids.