From Fruit Fly Scientist to Founder of a Biotech Startup

The fields of genetics and genomics have exploded since the landmark Human Genome Project began in 1990. Technological developments and falling costs have made population genetics endeavours more feasible, and numerous such studies have been initiated. Now, the focus is turning to deciphering our genes to identify those that are important for health and disease, a feat that will ultimately enable clinicians to more accurately predict a patient’s risk for disease and to tailor treatments for more successful outcomes.

A key name in the effort to bring human genetics research to the clinic in Singapore is Professor Liu Jianjun, Deputy Executive Director of A*STAR’s  Genome Institute of Singapore (GIS). In December 2020, Liu was awarded the President’s Science Award (PSA), one of Singapore’s highest honours given to scientists and engineers. His work on the genetics of Asian populations—currently grossly underrepresented in public research databases —has and continues to contribute to advancing medical research and the field of precision medicine at large.

Here, Liu discusses his interest in genetics, the impact of the research that contributed to his winning the PSA, and his plans going forward.

What drew you to study human genetics and to make it your life’s work?

For my PhD candidature at Duke University, I studied classical genetics, which uses genetics to understand species evolution. I used Drosophila, or the fruit fly, as a model. I remember, at one point, my mum asked me what I was studying. When she heard about the fruit flies, her response was, “Why are you studying that?”. That was when I realised that while fruit fly genetics and species evolution were interesting subjects for a doctorate thesis, it was somewhat removed from the lives of humans. So, for my postdoctoral research at Columbia University, I switched to studying human genetics, to try to have a more direct impact on human health.

One of the accomplishments that contributed to your winning the PSA was the identification of risk strains of Epstein-Barr virus (EBV) and its association with nasopharyngeal carcinoma (NPC). Can you share the story behind this discovery?

EBV has long been linked to NPC: it is one of the few viruses known to cause cancer in men; EBV is always found in patients’ tumour tissues. EBV infection is endemic and it is present in more than 90% of the world’s population, yet only  a small percentage of the world’s population developed NPC, and only in a particular geographical region; NPC has a higher prevalence in southern compared to northern China. We now know that the answer came down to genetics: like other viruses, EBV has different strains.

To draw better connections between EBV and how it causes NPC, we performed large-scale whole genome sequencing of many EBV strains and examined samples from different regions to determine whether a specific strain of EBV could be responsible for NPC. We found two strains in southern China that were so strong that a person carrying both strains is ten times more likely to develop NPC than the normal population. Our modelling analysis showed that these strains explained 80% of the risk of developing NPC in southern China.

This understanding has opened many clinical opportunities for applications to healthcare that may impact the lay person. For example, we are working on developing a screening programme to identify individuals carrying these EBV strains. Once identified, these affected individuals can be referred to specialists and followed up regularly at the clinics. This in turn allows for early diagnosis of NPC. Early stage NPC has a good survival rate of up to 95%, whereas the survival rate for late stage NPC (e.g. at stage three or four ) is dismal, at less than 50%. Therefore, early diagnosis is critical for NPC, but unfortunately, most NPC patients are currently diagnosed with late stage cancer. By enabling early diagnosis, our discovery can really transform the clinical management of NPC.

Your work on dapsone sensitivity has also had enormous impact. Can you tell us about this study?

This study forms a line of research called pharmacogenomics. For a long time, we have known that people respond differently to drug treatments, yet current clinical practice treats everyone the same. In the case of dapsone—a very effective treatment for leprosy—about 10–15% of patients develop fatal adverse drug reactions, known as dapsone hypersensitivity syndrome, or DHS. And doctors could not tell who would or would not develop DHS.

I performed a genetics study and identified a factor called HLA-B*13:01, which increases an individual’s risk of developing DHS by 30-fold. My students and I have now founded Nalagenetics, a startup, to take this finding related to dapsone from an academic setting into the commercial space. Through Nalagenetics, we are also working with the Indonesian Ministry of Health to establish a national screening programme, as Indonesia ranks among the top three countries with the highest rates of leprosy in the world. I think genetics and genomics can play a large role in the future of precision medicine. I hope that Nalagenetics will continue to develop more diagnostic tests and contribute to the precision medicine effort in Singapore.

What does winning the PSA mean to you and what do you hope to do next?

I see it as recognition of the impact of genetics on biomedical research. I think my work truly demonstrates how genetics can help advance our understanding of disease and also our response to treatment.

Moving forward, there are two main areas where I want to specifically focus my efforts on. The first is the National Precision Medicine program, where I will contribute through my role as the Deputy Executive Director of GIS. The second is related to my academic research. There are still questions I would like to pursue in my NPC/EBV research, particularly related to how recent strains of EBV have evolved in the population. I also want to further my work in cancer genetics.