Doctors today have more options in their medical toolkit to treat diseases, with advances in healthcare adding living cells to their arsenal. In cell-based immunotherapy, human immune cells are grown, modified and infused into patients, harnessing our body’s natural defenders to target cancer and other difficult-to-treat diseases.
However, an effective cell-based therapy doesn’t only depend on the type of cells used, but also on the nutrients the cells consume and how those nutrients are used. Known as metabolism, this vast network of chemical reactions occurs in every living cell and changes dynamically to modulate cellular function. The small molecules involved in these reactions are known as metabolites.
To design potent cell-based immunotherapies, A*STAR Bioprocessing Technology Institute (A*STAR BTI) Scientist Yu Hui Kang aims to understand both the biology of immune cells and the chemical reactions involving their metabolites. By building bridges between immunology and metabolomics, Kang and colleagues are optimising the metabolic networks of immune cells so that they can carry out the best cellular processes to combat disease.
In this interview with A*STAR Research, Kang discusses his interdisciplinary academic journey, how his experiences influence his work, and the role of metabolomics in advancing healthcare research.
1. Tell us about your journey in science.
I first pursued a traditional path in immunology as I wanted to work on a topic that was relevant to multiple diseases. Doing my PhD degree at a paediatric hospital allowed me to stay connected to that goal and gradually led me to value patient impact over journal publications—though we always strived for a balance between the two. I’m grateful to A*STAR for both its scholarship support and its strong emphasis on applying research for the benefit of Singapore.
Later, inspired by an A*STAR colleague, I decided to pivot towards analytical chemistry—metabolomics in particular. I’d been interested in how metabolism can shape immune cell function during my PhD studies, but found it difficult to understand metabolomics, a field that is critical to generating that insight. With my supervisor’s help, I joined the lab of a metabolic expert with in-house metabolomics capabilities. This marked the beginning of my interdisciplinary training; beyond metabolomics itself, I acquired a better understanding of the analytical, precision-focused approach to science— the skills of which I continue to apply today.
2. Why do you think metabolomics is an exciting field to be in?
Far from the static pathways you might have learned about in school, metabolism is a highly dynamic network, constantly changing to meet the body’s needs and functions. You can compare this network to road traffic, which shifts as traffic marshals direct different junctions. We are still discovering new ways in which metabolic traffic moves; metabolomics allows us to not only study these movement patterns, but to also reveal potential targets (junctions) for new therapeutics.
We now know that metabolism is a critical driver of many diseases, rather than a passive bystander. Obesity, diabetes and other common diseases in Singapore are linked to metabolic defects—the same ones that medicines such as metformin and GLP-1 agonists are designed to help restore. Further research is underway to test if these metabolic drugs also work for immune-based diseases.
3. What is the most memorable aspect of your interdisciplinary journey?
The most memorable part of my experience is cultivating a core trait of interdisciplinary researchers: the ability to integrate different fields to tackle key problems.
We conducted the metabolomics research alongside biological experiments on immune cells, which allowed me to refine the analytical or biological aspects as needed. Sometimes, this meant formulating new methods to detect specific metabolites; at other times, it involved utilising different approaches—such as bioinformatics and perturbation experiments—to validate the metabolomics. This constant crosstalk between disciplines helped us better understand each field and generate useful insights into the metabolic pathways immune cells use in diseases such as cancer.
4. Tell us about your current work at A*STAR BTI.
I work in A*STAR BTI’s Analytical Science & Technology (Metabolomics) group, where my main focus area is cell-based immunotherapy. These therapies remain complex and costly to manufacture, as cells are labour-intensive to generate and can vary significantly across processes and donors.
As cellular metabolism is an important source of this variability, a key part of my work involves monitoring and optimising metabolites during the biomanufacturing process to ensure product quality and reduce costs. We look for early indicators of successful metabolic states so that unsuccessful cultures can be terminated early, thereby minimising resource wastage. We also rationally fine-tune their diet (the media they grow in) to improve the odds of generating cells with ideal metabolic states.
This role is a great fit for my interdisciplinary skills as it allows me to apply immunology to understand the biological context behind processes, and analytical chemistry to improve precision and consistency in biomanufacturing.
5. What are your big goals in health research?
One of my goals is to foster a greater adoption of metabolism as an area of therapy. A common approach to disease treatment today is to alter biological pathways by modulating genes and proteins. While exciting and important, these modalities can be expensive. In contrast, metabolic pathways can be modified affordably through dietary changes or small molecules that target key enzymes. It would be great to see metabolism play a more prominent role in disease treatment, perhaps as a cost-effective addition to conventional approaches.
My second goal is to encourage greater consideration of the metabolite environment—culture media, for example—in immunology research and the development of immune-based medicines. When I was solely focused on immunology, I tended to prioritise cells and proteins, while metabolites were often an afterthought. Now, knowing that metabolites play an active role in immune function, I believe it’s essential for researchers to consider and optimise the environments in which our cells reside, to develop medicines that work potently within the body.
6. What advice would you give to other researchers interested in multiple fields?
First, find out more about the interdisciplinary path you’re interested in. This path can offer opportunities for innovation by breaking silos and revealing gaps that exist across fields. However, it’s important to find an environment that values boundary-spanning breadth. Research systems are typically organised around disciplines with emphasis on depth within a specific field, thus interdisciplinary researchers—who often don’t fit neatly into conventional lanes—may need to actively articulate the value of their integrative contributions. I’m grateful to have found a place at A*STAR BTI that values multidisciplinary collaboration.
Next, have a purposeful narrative when choosing your areas of focus. This will help you and others make better use of your skills, which is especially important when navigating less conventional paths.
Finally, try to connect with like-minded individuals. Interdisciplinary researchers are relatively uncommon in discipline-organised systems, so finding a community of people who share your interests can be incredibly helpful. I’m always happy to connect and continue these conversations.
