Dr Philip Yeung Man-lung
Associate Professor 
Department of Microbiology

“Hey Philip! Let me tell you a secret of how to become a great scientist.” this was the first topic presented to me by Dr. Kuan-Teh Jeang (“Teh” – a nickname called by his friends and colleagues; 1958 – 2013) in the first week after I started my post-doctoral training in his laboratory at The National Institute of Health (NIH), USA. As more than 20 post-doctoral fellows had successfully established their own laboratories and teams worldwide after graduating from Teh’s laboratory, I paid full attention to every word he said.

Teh was a renowned scientist who made significant contribution to our understanding of the molecular details of human immunodeficiency virus-1 (HIV-1) and human T cell leukemia virus-I (HTLV-I) replication, as well as disease-causing mechanisms of viral pathogenesis. While I was always amazed by the cutting-edge technologies that his team applied to resolve complicated biological problems, I worried that I was not sufficiently technically competent to handle such experiments alone. I honestly revealed to him my perceived strengths and weaknesses in an attempt to minimize the time for me to adapt to the new research environment. Within seconds, Teh assigned me projects that were completely beyond my expectations.

Despite the extreme pressure from adapting to this new environment, new research field, and unfamiliar experimental platforms, I upheld my principle of research integrity by including as many controls as possible. All experiments were independently repeated at least five times to ensure that the outcomes were reproducible. One of the many tasks Teh assigned to me was to repeat all the experiments generated by a preceding post-doctoral fellow who had been working in the field for over 10 years. Given the substantial number of experiments, I spent my time performing hundreds of transfection and luciferase assays daily, for several months. As expected, some deviations were introduced in some of the independent repeats of these experiments, as the sample processing time increased with the number of samples. Whenever I encountered this situation, I discarded the entire data set and repeated the test. After numerous “failures” to achieve a “perfect” set of data, I managed to break down a large-scale experiment into blocks of smaller-scale experiments. The skills I acquired during this exercise have helped me enormously in handling big data throughout my research career.

The environment at NIH allowed me to focus fully on my research. I mastered several cutting-edge technologies, including high-throughput sequencing and genome-wide loss-of-function knockdown screening. These technical platforms are useful tools to understand host-pathogen interactions. As a citizen of Hong Kong, China, I always consider of how I could utilize my knowledge to contribute to my hometown. After my post-doctoral training, I joined the laboratory of Prof. Kwok-Yung Yuen at the Department of Microbiology, The University of Hong Kong, as a Molecular Virologist. I was very excited to join his laboratory as the department had one of the best-equipped Biosafety Level 3 facilities in Asia. The faculty members of this department are a mixture of clinical and non-clinical scientists who facilitate the identification of disease-causing pathogens. In addition, research findings discovered in the laboratory can be seamlessly translated to clinical healthcare settings.

Prof. Yuen, an “Asian hero”, was concerned with emerging infectious diseases during the SARS epidemic in 2003. As the head of Department at the time I joined his laboratory, he suggested that I work on enteroviruses and coronaviruses, which are the most important emerging infectious viruses in the Asia-Pacific region. After confirming the research topics, I quickly identified all essential human factors that are important for enterovirus replication using a genome-wide loss-of-function knockdown approach. Notably, an inducible cellular receptor that can sensitize cells to a broad range of enteroviral infections was identified in this study. However, publishing these research findings was not straightforward. Despite multiple independent pieces of evidence demonstrating the receptor role of the identified human factor, many journals refused to send out this work for review because the human factor had been shown to be involved in other biological functions. After several attempts, I found a journal that agreed to review my work and it received positive comments. A commentary on my work has also been published by experts in the field. In addition, my study on the tissue tropism of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) provided new insights. Our work demonstrated that human kidney cells are highly susceptible to MERS-CoV infection, which could be clinically relevant given the high incidence of kidney failure in MERS-CoV-infected patients. Our study raised important concerns about the possible dissemination of MERS-CoV to the kidneys of patients. Since the publication of our work, post-mortem data have shown that the virus detected in the kidneys of MERS-CoV-infected patients. Our findings laid an important molecular virology foundation for studying emerging infectious viruses.

The emergence of SARS-CoV-2 in 2019 alerted us again to how little we know about virology. I was puzzled by how SARS-CoV-2 could cause such widespread disseminated infection within the body despite the lack of expression of angiotensin-converting enzyme 2 (ACE2) in many of the infected tissues. My research team successfully identified a new infection mechanism by which SARS-CoV-2 could enter cells by interacting with a soluble form of ACE2. As ACE2 normally enters the circulatory system to mediate its function in various organs, our discovery of this novel cell entry mechanism could potentially explain the broad tissue tropism of SARS-CoV-2, including organs that have low or no expression of ACE2.

“Science is not as welcoming of new ideas as it may seem.” Braben commented on the concept of Scientific Freedom. It takes years for people to accept a truly ground-breaking discoveries. A famous example is the Nobel Prize discovery of the Krebs cycle by Hans Krebs, which was once rejected by Nature. Taking a “high-risk” approach to research can be tough. However, I believe that such an approach can lead to truly revolutionary discoveries and will eventually meet with success. Therefore, I always encourage my team members to “work hard in silence, let success make the noise”- Frank Ocean.