For much of modern medicine’s history, the ‘one-size-fits-all’ approach reigned supreme—with drugs and treatments broadly prescribed to large groups of patients. Thanks to advances in genomics and gene editing—along with increasingly sophisticated molecular biology techniques—we now know that a more tailored approach is key to treatment success.
Promising to advance personalized medicine in Singapore and beyond, three researchers from A*STAR—Jianjun Liu, Wei Leong Chew and Si Hui Tan—were recognized at the 2020 President’s Science and Technology Awards (PSTA) and Young Scientist Awards (YSA) for their outstanding achievements in developing more effective treatments for various diseases.
Awarded annually since 2009, the PSTA represents the highest national honors that researchers in Singapore can receive. The awards are meant to recognize individuals or teams who have made invaluable contributions to the country’s vibrant research and development landscape.
Carefully chosen by key representatives from industry, academia and research, this year’s PSTA winners epitomize the best scientific talent Singapore has to offer.
The Young Scientist Awards (YSA), organized by the Singapore National Academy of Science and supported by A*STAR, recognize the accomplishments of researchers under 35, who have shown the potential to be world-class experts in their chosen fields.
Capturing Asia’s genetic diversity
Despite accounting for over half of the world’s inhabitants—a whopping 4.4 billion—Asian populations remain underrepresented in genetic studies. A 2019 analysis published in Cell revealed that of all the individuals included in genetic studies of disease to date, only 10 percent were Asian.
Seeking to address genetic research’s glaring diversity gap, Jianjun Liu—Deputy Executive Director of A*STAR’s Genome Institute of Singapore (GIS)—has made it his life’s mission to place Asian genomes under the spotlight and herald a revolution in precision medicine.
Take the ancient disease leprosy, a disfiguring infection caused by Mycobacterium leprae that causes skin lesions and sensory loss. While no longer an epidemic of biblical proportions, over 200,000 new leprosy cases are still diagnosed each year. One effective treatment for leprosy is the antibiotic, dapsone. However, the drug can provoke a potentially fatal reaction in hypersensitive patients.
Through genome-wide association studies, Liu and his team discovered an Asian-specific biomarker called HLA-B*1301 was associated with the onset of dapsone hypersensitivity syndrome (DHS). According to their analysis, individuals with one copy of the biomarker are 34 times more likely to develop DHS, while those with two copies are 101 times more susceptible to the syndrome than those without. Thanks to Liu’s pioneering work, leprosy patients are now screened for the presence of HLA-B*1301 before receiving dapsone.
Liu also helped identify specific strains of the Epstein-Barr virus (EBV) associated with nasopharyngeal carcinoma (NPC)—a nose cancer so common in South China that it is informally known as the ‘Cantonese cancer.’ By sequencing the genome of EBV isolates from patients and healthy people living in NPC-endemic regions, Liu and his team discovered two EBV variants that account for 83 percent of the risk of developing NPC. Similar to his leprosy research, these findings could be used to screen individuals and identify those who are at high risk for the cancer.
In his most ambitious project to date, Liu and his collaborators from the National University of Singapore, Duke-NUS Medical School and local public hospitals recently sequenced the genome of nearly 5,000 Singaporeans hailing from Chinese, Malay and Indian ethnic groups. Their findings represent the world’s largest genetic databank of Asian populations to date, capturing 80 percent of the region’s genetic diversity in the process.
For his pioneering contributions to the genetic studies of Asian populations, Liu was awarded the 2020 President’s Science Award (PSA). “This award is a recognition of the importance of studying Asian genetics,” he said. “The award also recognizes the great research environment at GIS and A*STAR.”
Even after winning the PSA, Liu has no plans of resting on his laurels. After all, there’s still much work left to do. As of writing, around half of the 10,000 individuals targeted by his team’s genome sequencing initiative have had their genomes sequenced. “Our study is just the beginning for the National Precision Medicine program,” said Liu. “A much bigger study will be launched soon.”
Liu also intends to intensify his efforts to sniff out the genetic roots of nose cancer. “We are working to discover additional EBV risk variants or strains in Southeast Asia, as well as develop biomarkers and diagnostic assays for population screening.” Indeed, by shining a much-needed light on Asia’s unique genetic heritage, Liu has cemented a legacy of his own.
Gearing up for gene editing
Less than a decade after CRISPR burst into the public imagination, the gene-editing technology had already garnered its pioneers Emmanuelle Charpentier and Jennifer Doudna the Nobel Prize. Considering that scientists often wait around 20 years or more for the coveted award, CRISPR’s fast-tracked recognition is a testament to its sheer impact on biological research.
Today, CRISPR has become a mainstay in molecular biology laboratories worldwide. As a Senior Research Scientist at GIS, Wei Leong Chew is rewriting the code of life by enhancing gene editing and gene therapy delivery techniques. For instance, Chew was one of the first to successfully achieve gene editing across multiple organs of live mammals—opening up possibilities for the correction of various genetic diseases. Previously, CRISPR had only been applied in cell culture.
Chew also provided early proof that CRISPR delivery with an adeno-associated virus (AAV) vector triggered an immune response in mice—providing an initial glimpse into the safety of CRISPR-based therapeutics. Accordingly, to safely bring these therapeutics from bench to bedside, his team is now working to predict and minimize the adverse immune reactions to gene editing.
In light of his seminal efforts to advance gene-editing therapy, Chew was recognized with the 2020 Young Scientist Award under the Biological & Biomedical Sciences category. “I am tremendously honored and humbled to be awarded,” he said. “This a strong testament to the excellent science that our team is doing. This also emphasizes the fantastic environment at A*STAR, where we can come together as one team to solve pressing issues in Singapore and globally.”
Much like Liu, Chew has no plans of resting anytime soon. “Our research is moving faster than ever before,” he shared. “We have recently developed a new class of precision gene editing technology, called C-to-G base editors, that changes a single letter within the human genome in unprecedented ways.” His team is also currently working on novel molecular assays, as well as therapeutics for diseases long considered incurable. By reassembling life’s building blocks, Chew is paving the way for better, safer and more effective medicines.
Stamping out cancer stem cells
Since their discovery in mice in 1981, stem cells have been widely touted as a panacea for diseases ranging from leukemia to vision loss. Despite their status as a miracle treatment, stem cells also have a sinister counterpart: cancer stem cells.
As indicated by their name, cancer stem cells possess characteristics associated with regular stem cells. That is, they can self-renew and give rise to the various cell types found in tumors. These cancer stem cells, therefore, act as a reservoir that can result in relapses. Unless these cancer stem cells are unequivocally eliminated, the tumor will continue to grow back—similar to how weeds repeatedly return time and time again.
Si Hui Tan, formerly a Research Scientist at Nick Barker’s laboratory at A*STAR’s Institute of Molecular Biology (IMB), has devoted her career to weeding out these cancer stem cells. “My interest in stem cells came to the fore because of the discovery of cancer stem cells when I was about to embark on my PhD,” she shared.
Focusing on gastric or stomach cancer, which is especially common in Asia, Tan identified aquaporin-5 (AQP5) as a new marker that can be used to isolate human stomach cells. Notably, AQP5 may also be a marker for gastric cancer stem cells—and an intriguing new target for drugs in development.
For her contributions to cancer and stem cell research, Tan received the 2020 Young Scientist Award under the Biological & Biomedical Sciences category. “It is heartening to see that purposeful and rigorous basic science is valued by our society,” said Tan. “Basic science is the key foundation for future translational discoveries.”
After making waves in cancer research at A*STAR, Tan is now leading a research team at local start-up Cargene Therapeutics. “We have a multidisciplinary team working on oligonucleotide therapy for various indications,” she explained. In oligonucleotide therapy, chemically synthesized nucleic acids silence gene expression by binding to a target nucleic acid.
Along with local quantum computing start-up Entropica Labs, Tan is also harnessing artificial intelligence to dole out personalized cancer diagnoses based on signaling pathways. With her innovative approach and drive for excellence, Tan will surely thrive in whatever field she chooses to explore.