Profile: Up-close with: Professor Lim Kah Leong

LKCMedicine’s new Vice-Dean of Research joins the School’s faculty this month and tells us about his lifelong passion for science, his life’s mission and his plans for the research faculty.

Interview by: Anne Loh, Assistant Director, Communications and Outreach

Q. Have you always been interested in science? 
I have always wanted to be a scientist since I was very young. In those days (i.e. in the 1970s), while my classmates were immersing themselves in their make-believe fairytale world (blame Enid Blyton, the JK Rowling during that era), I was curious about how things work and how diverse life is. My favourite book during my primary school days was one I had received as an award for doing well in science, entitled Bees, Wasps and Beetles.  I have always been fascinated by all creatures big and small. Much to my mum’s chagrin, I was keeping ants in a sandbox as a hobby to observe their behaviour. I knew then that I will probably not be happy doing anything else other than being a scientist.

Q. When did your interest in research begin? (an exploding test tube always helps)

Indeed, an exploding test tube always helps if you live to tell the world how it had exploded. I was once really curious about how a cigarette lighter works (my dad was a heavy smoker), specifically about the nature of the mysterious liquid inside the lighter that produces the flame when it comes into contact with the spark of the tinderbox. I wanted to pour the liquid out to inspect it more closely. You know what I did? I was stupid enough to use a flame-heated wire to pierce through the plastic pocket lighter container. The pressurised flammable liquid immediately gushed out from the container and hit my eyes in a fast and furious manner. Thank goodness the pressurised flammable liquid did not ignite upon contact with the heated wire! Yes, I lived to tell the tale, and I thought after that chilling episode that I had better do my research properly before attempting anything too dangerous out of pure curiosity. I am, after all, not a feline. 

Q. When was the “eureka” moment when you realised you have made the right decision to dedicate your life to research?
Right after graduation, I did a detour on purpose to take up an administrative position just to convince myself that it would not be my cup of tea. To cut a long story short, I became a management executive at the (now defunct) Toa Payoh Hospital in charge of the operations of its Specialist Outpatient Clinics. A phone call from my friend in research led to my resignation from the hospital three months later. It was not at all due to the persuasive power of my friend at the other end of the phone line but what he had done, which was really cunning. He was popping Eppendorf tubes (which we routinely use in the laboratory) to let me hear the sound of what I had dearly missed. I then packed up and left to join the Institute of Molecular and Cell Biology (IMCB) to pursue my PhD studies. And yes, that was my “eureka” moment. Paradoxically, my exposure to hospital patients during my brief stint at Toa Payoh Hospital made me more determined to return to the laboratory to find the best therapy for them.

Q. But you went further post-PhD?  
After graduating from IMCB in 1999, I left for the States to pursue my postdoctoral training firstly at the Department of Pathology in Harvard Medical School (2000-2001), and subsequently at the Department of Neurology in Johns Hopkins University School of Medicine (2001-2002) where I worked on the topic of Parkinson’s disease. I returned to Singapore in 2002 to start my independent career as a scientist at the National Neuroscience Institute. The long-term primary goal of my laboratory is to elucidate the molecular events underlying Parkinson’s and related neurodegenerative diseases, with the view to develop novel therapies aimed at effectively treating these debilitating disorders. We adopt a multi-pronged approach, including the use of different disease models such as Drosophila, mouse and patient-derived human neurons, to achieve our objectives. 

Q. Why did you decide to specialise in Parkinson’s research? 
You could say that part of the reason is related to my pragmatism as a Singaporean. I was in the cancer field during my postgraduate years and every Tom, Dick and Harry was also in the same field. To “future-proof” myself, I thought I should branch into a new field and a topic that Singapore would recognise, with time, to be an important one to focus on. While I was contemplating this, I learnt that the father of a close friend of mine was stricken with Parkinson’s disease (PD). When I found out more about PD, I realised that it is a terrible disease that progressively robs the sufferer’s volition to perform basic movements, likened to being a prisoner trapped in his/her own body. I was (still am) motivated to find a cure. Moreover, I was (still am) fascinated by the insidious and selective degeneration of an exquisite population of neurons in PD. Why do these neurons die in PD while others are spared remains a burning question inside my head after all these years. Nearly two decades later since I first embarked on PD research, a picture of the tapestry of interwoven molecular events underlying the pathogenesis of the disease is now emerging and we are slowly making sense out of the apparent chaos.

Q. You co-led the creation of the first two-photon, small molecule fluorogenic probe in 2014. Is this a turning point for PD (and mental health) research? 
I would not say that the discovery was a turning point for PD research. Rather, it represents a starting point for the development of a diagnostic method to detect the disease. It is well known that drug candidates for neurological disorders have an extremely high failure rate in clinical trials (99.6 per cent compared to 81 per cent for cancer). A major contributor to this is the lack of good detection methods for brain diseases that makes clinical trials difficult and costly. There is no doubt that targeting neurological disorders prior to or immediately after disease onset would significantly improve the much-needed success of pharmacological strategies. The challenge is to develop a reliable method to detect the disease at an early (or better still, preclinical) stage, which remains a critical unmet need. The probe that we have developed provides an important starting point for using small molecule imaging techniques to explore disease further at the organism level, and in fact, opens prospects for non-invasive imaging-based diagnostic applications. We have demonstrated that it works well with blood samples derived from PD patients. Encouraged by this result, we are currently developing a PD diagnostic chip for clinical applications.

Q. Will you continue with research into PD in LKCMedicine? Which other areas of mental health are you interested in?
Yes, most definitely. We are also working with the dementia research team at LKCMedicine led by Professor George Augustine to understand the circuitry defects responsible for Alzheimer’s disease and other memory disorders, with the view to elucidate a common disease-related circuitry signature that underlies various forms of dementias.

Q. Collaboration is the buzzword in research, it seems, riding on multidisciplinary wings. Do you think this is the way to make a great leap forward?
Certainly. Pardon me for sounding clichéd but I do believe in the philosophy that “If you want to go fast, go alone but If you want to go far, go together”. The way scientific research is being done has changed tremendously in the past decades. Very few groups, if at all, can afford to function in silos. The merit of multidisciplinary collaborations is that it allows research performers from different domain expertise to leverage on each other’s strengths to achieve common goals that they otherwise would not be able to achieve alone. Cross-domain collaborations are particularly important for Singapore, which, at the end of the day, is a small country with limited resources. We need to constantly think of ways to help maximise research productivity and minimise duplication of efforts. Science is a collaborative enterprise. Collaboration, not competition, is therefore the way to go.

Q. What do you think of Louis Pasteur’s saying that “Chance favours only the prepared mind” as a scientist and researcher?
Inasmuch as we appreciate that serendipity plays a crucial role in science, the unprepared mind is likely to dismiss accidental observations as blips on the radar. For unexpected findings to have a happy ending, the mind needs to be receptive to phenomenon that at first glance may appear capricious, so that we are always primed to discover the unexpected.

Q. Who have been your influencers or mentors, whether in work or life?
People at all levels and from all walks of life whom I have the privilege to interact with. They are the mirrors that allow me to see myself from different angles and upon which I could reflect on how I could do things better. 

Q. What is your proudest accomplishment so far?
Receiving the President Science Award last September was definitely a highlight of my career. Being a longstanding member of the national Parkinson’s disease research team, I was extremely proud that our efforts over the years have been recognised. It was a great honour and privilege to accept the award on stage, handed personally to me by our country’s President, Madam Halimah Yacob.

Q. How will you wind down from a research high?
I don’t intend to. Although I am cognisant of the heavy administrative demands of my new role, I see my research as a complement and not as an impediment. Indeed, staying connected to laboratory research would allow me to feel the pulse of science better, which would in turn help me to formulate better research strategies for the School. 

Q. What would you tell young researchers who are hitting the wall? 
Never give up. If you hit the wall long enough, it will break, and you will have your breakthrough. Never stop believing in yourself.

Q. What is the best advice you have ever received?
“Our greatest glory is not in never falling, but in rising every time we fall.” A friend gave me a homemade bookmark bearing this quote when I was in high school. It has been my life’s philosophy ever since. 

Q. Was there a life-defining incident that you could tell us about? What has it taught you?
Yes, when my electrocardiogram (ECG) showed an abnormal pattern in a routine medical check-up. Although a series of tests later indicated that there is no cause for major concern, it served as a wake-up call for me to take things in my stride and take time to smell the roses. 

Q. What would you have rather been, if you hadn’t gone into research?  

Q. When you think about the future in terms of the work, does it give you a sense of hope?
It gives me a sense of purpose, especially to generate hope for a better tomorrow for others.

Q. What are you looking forward to in your move to LKCMedicine?
Notwithstanding that LKCMedicine is arguably still at its nascent stage of development, the School is already populated with a significant number of extremely energetic and talented people. I am excitedly looking forward to working together with everyone at LKCMedicine to help sculpt the scientific culture and steer the ship towards becoming a global leader in research. At the same time, I am also looking forward to further strengthening the collaboration with our healthcare partners, with the view to catalyse the transformation of healthcare delivery.

Q. Do you have any passions/hobbies that make you better at what you do? 
I enjoy my weekend swim, which I take as a form of underwater meditation that helps me put things into better perspective.