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We are extremely proud to present four of our SIgN-tists who have been named as Highly Cited Researchers in 2020 by Clarivate.

Congratulations to Dr. Subhra K. Biswas (3rd consecutive award since 2019), Dr. Chen Jinmiao (2nd consecutive award since 2020), Dr. Florent Ginhoux (6th consecutive award since 2016), and Dr. Ng Lai Guan (2nd consecutive award since 2020) for their outstanding contributions to the field of immunology!

We are especially heartened to see more of our researchers being recognised for their excellent work, and for continued recognition of the work of our established PIs among the global community of immunology researchers We look forward to a growing number of impactful scientific works from their labs and our SIgN-tists which will continue to push scientific frontiers!

Check out their profiles among A*STAR list of highly cited researchers: https://www.a-star.edu.sg/Research/our-people/hcr

Singaporean researchers from Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR)’s Genome Institute of Singapore (GIS) have developed the world's largest and highest-resolution atlas of gastric cancer. Additional collaborators include the Singapore Immunology Network and the Cancer Science Institute of Singapore.

This world’s largest analysis of gastric tumour cells would provide a launchpad for scientists to plan more effective therapies for this type of cancer. Findings from the study have shown new insights into how gastric cancers progress and how tumours from separate patients differ from one another.

Reported in: Biospace

Scientists in Singapore have assembled the world’s largest and highest-resolution atlas of gastric cancer. The research was led by Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR)’s Genome Institute of Singapore (GIS), involving collaborators from the National University Health System (NUHS), A*STAR’s Singapore Immunology Network (SIgN) and Institute of Molecular and Cell Biology (IMCB), the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), and Kumamoto University, Japan.

The atlas provides, at the level of single cells, new insights into how gastric cancers progress and how tumours from separate patients differ from one another.

Gastric cancer remains a significant cause of cancer death in Singapore, particularly in males. Researchers found more than 30 different cell types, some of which had not been detected in gastric tumours before. This information may yield pathways that can be exploited for early cancer detection and drug development.

Reported in: BioSpectrum Asia

A team of international scientists and clinical experts have unraveled a new cell type in human skin that contributes to inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO). The team hails from A*STAR's Singapore Immunology Network (SIgN), in collaboration with the Skin Research Institute of Singapore (SRIS), Singapore's National Skin Centre, Department of Dermatology, Kyoto University Graduate School of Medicine, Japan, and industry partner Galderma.

Dr. Florent Ginhoux, senior principal investigator, SIgN, and last author of the study said, "The findings from this study are significant as it will allow the design of new strategies to target or modulate myeloid cell populations for better health outcomes for patients of atopic dermatitis and psoriasis."

"The roles of antigen-presenting cells in the development of inflammatory skin diseases remain unclear. This study clearly revealed the functions of each antigen-presenting cell subset, which is very informative and valuable to understand the pathogenesis of atopic dermatitis and psoriasis. We expect that this study will lead to the design of new treatment for refractory inflammatory skin diseases." said Prof Kenji Kabashima, Adjunct Principal Investigator from SIgN and SRIS.

Reported in: Phys.org, EurekAlert! Science News

The number of deaths surged in Singapore, even as vaccination rates have gone up. A new strain of the Delta virus has caused "a very rapid exponential growth of cases and in large numbers", as it spreads more easily both in people who have been vaccinated and those who are not vaccinated, though those who have been fully vaccinated are less likely to suffer from severe illness.

Associate Professor Ren Ee Chee, principal investigator at the Singapore Immunology Network at the Agency for Science, Technology and Research (A*STAR), explained that a vaccine trains the body's immune system, specifically the B and T cells, to eliminate a virus. "Memory B cells will be triggered by an infection to produce large amounts of antibodies rapidly, while T cells directly destroy virus-infected tissues. This dampens the impact of infection, hampering the virus from overwhelming the lungs and other vital organs. Thus, a fully vaccinated individual who becomes seriously ill would have a better chance of full recovery as compared with an unvaccinated person."

Reported in: The Straits Times Online, AsiaOne

A*STAR’s Infectious Disease Laboratory (ID Labs) and Singapore Immunology Network (SIgN), together with National University of Singapore and Duke-National University School of Medicine, is supporting the first long-term study titled "Singapore COVID-19 Vaccine Immune Response and Protection Study" (SCOPE), conducted by the National Center for Infectious Diseases (NCID). The NCID has launched two follow-up surveys of people who received Pfizer vaccines and found that most of them had a fairly good immune response after vaccination. Researchers hope to understand their risk of infection and determine how vaccines can protect high-risk groups when COVID-19 becomes endemic.

Reported in: Lianhe Zaobao Online

Blood clots can turn fatal, and risk factors for developing these clots include obesity and severe infection. In a study by A*STAR Singapore Immunology Network (SIgN), Nanyang Technological University (NTU), and the National Centre for Infectious Diseases (NCID), researchers found that COVID-19 patients also have a higher risk for developing blood clots.

Blood samples from 30 patients who had recovered from mild, moderate and severe Covid-19 were collected one month after they had been discharged from the hospital. All of them were found to have blood vessel damage, which could trigger the formation of blood clots.

Reported in: The Straits Times Online

Dr. Florent Ginhoux from A*STAR's Singapore Immunology Network (SIgN), Professor Jerry Chan from KK Women's and Children's Hospital (KKH), Professor Salvatore Albani from the SingHealth Duke-NUS Translational Immunology Institute, and collaborators from Cambridge University identified live microbes across fetal organs that stimulate the activation of fetal T-cells during the second trimester of gestation. Their study published in the scientific journal, Cell, on 24 June 2021. Dr. Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said that these findings have wider implications in understanding the key factors involved in fetal immune system development and priming in utero, which may set the basis for life-long human health and immunity of the organism.

Reported in: Phys.org

Certain types of Covid-19-neutralising antibodies - which prevent the Sars-CoV-2 virus from infecting a person's cells - may end up worsening the disease. A team of researchers from the Agency for Science, Technology and Research (A*STAR), in collaboration with the QBI Coronavirus Research Group at the University of California, San Francisco, University of Lyon and DSO National Laboratories, discovered that some neutralising antibodies inhibit syncytia, while others drastically enhance it. This entails using a viral spike protein as a "bait" to fish out the relevant antibodies that bind to it, said Dr Wang Cheng-I, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN) and one of the authors of the study. Dr Wang said that his team is now actively developing the antibody into a Covid-19 therapeutic. While a lot more work has to be done to understand what is involved, the fact that the two types of antibodies - one that inhibits syncytia and one that enhances it - can be found in both infected and vaccinated individuals has "profound implications" on how Covid-19 treatments should be designed. This is especially important, given the "ever-mutating nature" of the Sars-CoV-2 virus, said Dr Wang.

Reported in: The Straits Times

Macrophages arise early during embryonic development and play important in tissue development and functions. Here, scientists from Harvard Medical School, in collaboration with Dr Florent Ginhoux and Dr Peter See from SIgN/A*STAR, discovered an additional function of embryonic colon macrophages, showing they control invariant natural killer T (iNKT) cell seeding in the gut. This study uncovers a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota, and reveals an important postnatal function of macrophages that emerge in fetal life.

The Singapore Food Agency (SFA) will fund 12 research projects on sustainable urban food production, one of which aims to develop a vaccine against the scale drop disease virus in Asian sea bass, which has been touted to be the "salmon of the tropics". The research proposal is an initiative of the Agency for Science, Technology and Research (A*STAR) and UVaxx, a firm that develops vaccines for use in aquaculture. Associate Professor Ren Ee Chee, a principal investigator at A*STAR's Singapore Immunology Network who is involved in the project, said scale drop disease is one of the most common diseases among sea bass. Infected fish show symptoms such as lethargy and severe scale loss, and the disease frequently results in the loss of 50 to 100 per cent of an infected batch. He added: "Vaccinated fish can be healthier, grow to a larger size, and can be harvested without significant loss."

Reported in: The Straits Times Online

People who have recovered from COVID-19 may be at risk of developing blood clots due to a lingering and overactive immune response, according to a study led by NTU scientists. The team, comprising researchers from NTU, Agency for Science, Technology and Research’s (A*STAR) Singapore Immunology Network (SIgN), and the National Centre of Infectious Diseases, Singapore (NCID), collected and analysed blood samples from 30 COVID-19 patients a month after they had recovered from the infection and were discharged from hospital. Researchers hypothesise that the body's immune system, which was activated to fight the virus, remains overactive and activated even after recovery. This persistently activated immune responses may attack blood vessels, causing more damage and increasing the risk of blood clot formation further.

Reported in: BioSpectrum Asia, AsiaOne

People who have recovered from COVID-19, especially those with pre-existing cardiovascular conditions, may be at risk of developing blood clots due to a lingering and overactive immune response, a Singapore study has found. The study, led by Nanyang Technological University (NTU) scientists, investigated the possible link between COVID-19 and an increased risk of blood clot formation, shedding light on the medium- and long-term consequences of infection, or “long-haul COVID". Researchers found signs of blood vessel damage in all 30 patients, possibly from a lingering immune response. "Leakage from these damaged vessels triggers the formation of blood clots that may result in the sort of complications seen in the patients during hospitalisation," NTU said.
 
One of the co-authors Professor Lisa Ng, executive director of A*STAR Infectious Diseases Labs, said: "We found that COVID-19 patients with vascular complications have a higher frequency of T cells, which may in turn attack the blood vessels. Preventive therapy may be needed for these patients.” The team comprised researchers from NTU, A*STAR’s Singapore Immunology Network, and the National Centre of Infectious Diseases. The team is now investigating the longer-term effects of COVID-19 in patients who have recovered from the infection for at least six months or longer.

Reported in: ChannelNewsAsia Online, EurekAlert! Science News, The Straits Times Online, TODAY Online, Berita Harian, The New Paper

A recent local study found that pregnant women may pass their allergies to their foetuses. This research could help the medical profession to formulate preventive measures in the future to reduce the incidence of allergies in newborns during pregnancy. A local medical study published in the Science academic journal last year found that the immunoglobulin E antibody (referred to as IgE) that triggers allergic reactions can pass through the placenta and enter the foetus. This is the result of a survey jointly published by the Singapore Science and Technology Research Council, KK Women's and Children's Hospital and Duke-National University of Singapore School of Medicine.

Dr Florent Ginhoux, senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN), pointed out that at present, people have very limited understanding of the mast cells that exist in the early stages of the developing foetus. This study found that the foetal mast cells will mature phenotypically during the mother's pregnancy, and the maternal IgE can pass through the placenta and cause foetal allergies.

Reported in: Lianhe Zaobao Online

Clinicians and scientists from Singapore shared exciting new data on lung cancer treatment in the Asian population at the World Conference on Lung Cancer Singapore, last week. The Lung Cancer OF-LCG Programme is led and championed by leading clinicians and scientists from major healthcare institutions and research institutes from the Agency for Science, Technology and Research (A*STAR) including the Singapore Immunology Network (SIgN) and the Genome Institute of Singapore (GIS).

The creation of THOR, a multi-omics genomics platform that hosts thousands of lung cancer samples was presented at the Conference by Dr Anders Skanderup. Dr Skanderup, a scientist from GIS, who is the Big Data Theme lead on the Lung Cancer OF-LCG Programme and a member of the Conference's scientific committee, said, "Our work highlights the importance of integrated databases for use by local clinicians and scientists to facilitate collaborations and make new discoveries, as well as helping advance precision medicine.

Researchers from the Agency for Science, Technology and Research (A*STAR), DSO National Laboratories, the University of California, San Francisco, and the University of Lyon in France found that a series of neutralising antibodies against SARS-CoV-2 that potently block binding to the host receptor ACE2 are found to either enhance or inhibit virus spike-mediated membrane fusion and the formation of syncytia, a sign of tissue damage in COVID-19 patients.

Dr. Wang Cheng I, senior principal investigator of Singapore Immunology Network, said, “The degree of cell fusion is related to the severity of the patient's coronary symptoms. The more cells fuse, the more serious the disease. We found that some antibodies can block the combination of viruses and cells and avoid cell fusion at the same time, but some antibodies enhance cell fusion while avoiding the combination of viruses and cells. The research will provide guidelines for developers of antibody therapy programs to understand the differences in antibodies in vivo. When designing therapeutic programs, antibodies that can avoid both cell binding and cell fusion should be selected.”

Scientific Media Alert

9 March 2021, Singapore – Dr Florent Ginhoux, Dr Ng Lai Guan, and Dr Melissa Ng from A*STAR’s Singapore Immunology Network (SIgN), together with collaborators from Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China have found a new subset of gut cells that organise the intestinal stem cell niche, which is important for tissue repair. The study was published in the scientific journal, Nature on 3 March 2021.

These gut cells protect the colon from acute injury via the ROS–MAP3K2–KLF2–RSPO1 axis and hence are termed MAP3K2-regulated intestinal stromal cells (MRISC). Future investigation of MRISCs for their potential roles in restraining intestinal inflammation and pathology as well as their identification in human tissues and how to mobilise them could offer new therapeutic strategies to treat inflammatory bowel disease and colitis-associated colorectal cancer.

Colorectal cancer is cancer of the colon (the main part of the large intestine) and the rectum (the passageway connecting the colon to the anus). It is the top killer in Singapore, affecting more than 1,200 cases each year¹. Inflammatory bowel disease (IBD) can strike at any age, although most sufferers are diagnosed between the ages of 20 and 40 years².

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. A subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs) show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. Their results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.

Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, “The identification of such population of cells that can modulate the gut stem cell niche offers new therapeutical perspectives for gut disorders and we are going to investigate their presence and functions in human tissues.”

Professor Bing Su, Director, Shanghai Institute of Immunology and co-last author of the study added, “Our study also opens new avenues for studying the roles of these stromal cell subsets not only in gastrointestinal system, but also in many other systems for example immune or neuron systems, both in animal models and in human disease settings.”

More information on the study, “MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche” can be found via the team’s published paper in Nature: https://doi.org/10.1038/s41586-021-03283-y

Singapore kicked off its COVID-19 vaccinations for seniors aged 70 and above last week. Professor Lam Kong Peng, executive director of the Singapore Immunology Network (SIgN) under the Agency for Science, Technology and Research (A*STAR), and Dr Zhang Biyan, SIgN immunology research fellow, answered questions on whether there are benefits in receiving the vaccine early, and how important is it for the elderly to get their shots.

Scientists are studying the similarities between long COVID and ongoing symptoms experienced by survivors of Ebola and Chikungunya virus in the hope of devising new treatments to improve their health. Like patients with long COVID, survivors of those other, relatively new human viruses, often experience lingering symptoms which can make it difficult to work or function in everyday life.

Lisa Ng, senior principal investigator at the Singapore Immunology Network (SIgN), has done some studies in people who’ve recovered from Chikungunya virus. She stresses that Chikungunya is very different to COVID-19; although debilitating, it rarely causes severe disease or respiratory syndromes. Ng’s studies suggest T helper cells may be contributing to ongoing inflammation in the joints of people who’ve recovered from Chikungunya. Such insights could lead to potential treatments, such as the repurposing of existing anti-inflammatory drugs, or the development of new immunotherapies for such post-viral syndromes.

About 5 per cent of available vaccine stocks at any point in time should be set aside for people working in areas critical to Singapore's functioning, said the expert committee on COVID-19 vaccination. This was among the key recommendations made by the expert committee, and the Ministry of Health (MOH) said that the government has accepted the committee’s recommendations in full. The expert committee was tasked by MOH in October to devise a vaccine strategy for Singapore. Professor Laurent Renia, executive director and senior principal investigator at the Agency for Science, Technology and Research (A*STAR) Infectious Diseases Laboratories, and Associate Professor Ren Ee Chee, principal investigator at A*STAR’s Singapore Immunology Network (SIgN), are among the members of the committee.

Bacteria and viruses have got smarter, and some diseases seem to be threatening a comeback. With tried and tested defences losing the race against infections, the series Disease Hunters uncovers the novel treatments coming up. 
 
One disease that genetic engineering has shown promise against is dengue. One of the challenges to vaccinate against dengue is that the virus changes shape under different conditions, resulting in four serotypes. 
 
The Agency for Science, Technology and Research’s (A*STAR) Singapore Immunology Network (SIgN) is in the advanced stages of developing an antibody that is effective against all four serotypes of dengue. The antibody attaches to structures on the virus like a “key entering the lock”, said Laurent Renia, the former executive director of SIgN and current executive director of the A*STAR Infectious Diseases Laboratories. This, in turn, triggers the immune system to destroy the virus.

With more than 200 potential Covid-19 vaccines being developed globally, we are inundated each day with news on the latest developments. Covid-19 fuelled the development of an unprecedented number of vaccine platforms, some of which have never before been approved for use in humans. From the outset, it was important to address multiple concerns. In an opinion editorial article, Professors Benjamin Seet and Ren Ee Chee, who are both members of the Ministry of Health's expert committee on Covid-19 vaccination, shared the process and challenges of reviewing more than 40 vaccine candidates over the past seven months.

Professor Ren Ee Chee is an immunologist, and principal investigator at the Singapore Immunology Network (SIgN), under the Agency for Science, Technology and Research (A*STAR), and adjunct associate professor with the Yong Loo Lin School of Medicine at the National University of Singapore.

This ScienceTalk piece about COVID-19 treatments and their role in the war against the pandemic was co-authored by the Experimental Drug Development Centre’s (EDDC) Chief Executive Officer Professor Damian O’Connell, and the National Centre for Infectious Diseases’ (NCID) Associate Professor David Lye.

The article highlights different therapeutic approaches to treating COVID-19, plus global and local efforts to develop therapeutics against COVID-19. In Singapore, A*STAR is collaborating with Chugai Pharmabody Research, a research centre of Japan's Chugai Group in Singapore, on joint research on a therapeutic antibody to fight COVID-19. The project focuses on a potential therapeutic antibody discovered by a research team at A*STAR's Singapore Immunology Network (SIgN), which worked in close collaboration with DSO National Laboratories at their high-containment Biosafety Level-3 facilities. 

Meanwhile, EDDC is supporting several local programmes to address the immediate situation at hand with a mid-to-long term view in mind. Apart from active in-house drug discovery, its programmes include sharing technical know-how on drug development with local players, participating in the national discourse on COVID-19 in several forums, supporting the development of diagnostic assays (particularly the Fortitude Kit for detecting SARS-CoV-2) as well as the clinical translation of novel monocloncal antibodies (mAbs) against SARS-CoV-2 from bench to bedside. 

EDDC’s discovery programme on small molecules focuses on developing a broad-spectrum antiviral drug to counter future novel infectious disease outbreaks, under an accelerated timeframe. EDDC is also supporting local biotech companies – ASLAN pharmaceuticals, AUM Biosciences, and Rhea Pharmaceutical Sciences – to test their compounds as possible treatments for COVID-19.

In addition, EDDC is working with DSO in the pre-clinical and clinical development of a potential COVID-19 therapeutic called AOD01, which is a SARS-CoV-2 neutralising mAb. The safety and pharmacokinetics of AOD01 will be evaluated in healthy subjects during clinical studies in Singapore, followed by looking at the drug's antiviral activity in COVID-19 patients. 

The Ministry of Health (MOH) has appointed a 14-member committee to make recommendations to the Government on its Covid-19 vaccination strategy, and ensure the safe and effective use of vaccines against the coronavirus. The committee's role is to consider the most up-to-date information and assessment of Covid-19 vaccines, including closely monitoring the global vaccine development landscape and stance of agencies such as the World Health Organisation. 
 
Professor Laurent Renia, executive director and senior principal investigator at Infectious Diseases Laboratories, and senior principal investigator at Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), together with Associate Professor Ren Ee Chee, principal investigator at the Singapore Immunology Network, are named as part of the 14-member committee. 

Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women's and Children's Hospital (KKH) and Duke-NUS Medical School in Singapore reported in the journal Science on 30 October. 

Currently, there is a significant lack of knowledge on mast cells that are present early on in the developing fetus, notes Florent Ginhoux, study co-author and senior principal investigator at A*STAR's Singapore Immunology Network.

The research, in laboratory studies, also demonstrated that maternal IgE can bind to human fetal mast cells, suggesting that a similar crossover takes place in humans.

The findings open up the possibility of new intervention strategies to prevent allergies being passed from mother to child. "We could identify highly allergic mothers and try to reduce their IgE levels during pregnancy by removing them from blood circulation," Ginhoux tells SciDev.Net.

Scientists from A*STAR’s Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), National Cancer Centre Singapore (NCCS) and KK Women’s and Children’s Hospital (KKH) uncover interactions involved in foetal-like reprogramming of liver cancer cells. By conducting a comparative study that involved mapping 200,000 single human liver cells from foetal development to terminal liver cancer, the researchers discovered two new foetal-associated cell types that were present in the tumour ecosystem of HCC. “Our research underscores a fundamental understanding of how early developmental processes can be hijacked by cancers in order to facilitate their own growth, and escape immune surveillance,” said Dr. Ramanuj DasGupta, the Senior Group Leader at GIS and the lead corresponding author of the study.

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB), in collaboration with doctors from KK Women’s and Children’s Hospital (KKH), have discovered a new immune pathway based on an investigation of severe immunodeficiency caused by a novel mutation in the NFKBIA gene. The findings were published in The Journal of Clinical Investigation. 

Scientists at A*STAR identified a new genetic variant in NFKBIA that changed the levels of soluble proteins called cytokines. Abnormally high production of one cytokine, IL-1β, was identified as the key derangement. In addition, the research team, along with Singapore Immunology Network (SIgN) discovered a previously unknown pathway, which controls IL-1β production. These findings have implications for the development of treatments against liver disease and cancer that target this novel pathway. 

Dr John Connolly, a Research Director at IMCB, said that the mutation found in the study is the only mutation in which hyper-production of IL-1β, severe liver cholestasis and systemic inflammation were documented. He added that the mutation limits immune responses via the suppression of many pro-inflammatory cytokines and causes over-production of IL-1β, leading to liver damage and inflammation. Hence, the use of this bedside-to-bench approach to identify the underlying genetic causes of immunodeficiency diseases, previously unknown pathways which control immune responses can be revealed. These then serve as targets for personalised treatment strategies.

Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women's and Children's Hospital (KKH) and Duke-NUS Medical School in Singapore reported this week in the journal Science. The study shows that the key antibody responsible for triggering allergic reactions, immunoglobulin E (IgE), can cross the placenta and enter the fetus. The study findings can potentially open new intervention strategies to limit such transfer to minimize the occurrence of neonatal allergies.

Dr. Florent Ginhoux, senior principal investigator at A*STAR's Singapore Immunology Network (SIgN), said, "There is currently a significant lack of knowledge on mast cells that are present early on in the developing fetus. Here, we discovered that fetal mast cells phenotypically mature through the course of pregnancy, and can be sensitized by IgE of maternal origin that cross the placental barrier. The study suggests that a highly allergic pregnant mother may potentially transfer her IgE to her baby that consequently develop allergic reactions when exposed to the first time to the allergen." 

Researchers from A*STAR’s Singapore Immunology Network (SIgN), together with international collaborators have discovered blood markers that could predict COVID-19 severity and/or risk in patients. The study was published in the scientific journal, Cell on 17 September 2020. The study identified biomarkers (calprotectin) and cellular markers (monocyte and neutrophil subsets) in the blood of COVID-19 patients that could potentially be used as predictors or risk factors of progression from mild to severe forms of the disease. Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, "Our study integrates frequencies of non-classical monocytes and immature neutrophils with calprotectin plasma levels as robust biomarkers of COVID-19 severity and suggests potential therapeutic strategies targeting calprotectin to alleviate severe COVID-19.”

The coronavirus pandemic may have taken much of the world by surprise, but such outbreaks are nothing new. At the frontlines of the age-old battle against disease-causing pathogens are scientists like Professor Lisa Ng, who is a senior principal investigator at the Agency for Science, Technology and Research’s (A*STAR) Singapore Immunology Network (SIgN). Since her days as young biochemistry undergraduate at the University of Manchester Institute of Science and Technology, Ng already had a keen interest in infectious diseases. This led her to pursue a PhD in molecular virology at the National University of Singapore, followed by a postdoctoral stint at A*STAR’s Genome Institute of Singapore. 

Over the next two decades, Ng has grown to play a pivotal role in Singapore’s scientific response to infectious diseases. She was recruited to be part of the A*STAR diagnostic research team during the 2003 SARS epidemic. Along with her colleagues, Ng developed a test that could detect SARS-CoV in patient blood samples. In the following years, she also helped create diagnostic assays for bird flu and Zika, on top of establishing biomarkers for chikungunya.

A team of researchers and clinician-scientists from A*STAR’s Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), National Cancer Centre Singapore (NCCS), and KK Women’s and Children’s Hospital (KKH), have identified a pivotal “fetal-like” reprogramming of the tumour ecosystem in human hepatocellular carcinoma (HCC). The study leveraged the platform established by the National Medical Research Council (NMRC) Translational and Clinical Research (TCR) Flagship Programme in Liver Cancer and was recently published in Cell on 24 September 2020. The team identified the reappearance of fetal-like endothelial cells that are responsible for blood supply, and fetal-like macrophages, an immune cell type that serves as the body’s first line of defence against pathogens, but are also associated with tissue homeostasis.

Researchers from A*STAR’s Singapore Immunology Network (SIgN), together with international collaborators have discovered blood markers that could predict COVID-19 severity and/or risk in patients. The study was published in the scientific journal, Cell on 17 September 2020. The study identified biomarkers (calprotectin) and cellular markers (monocyte and neutrophil subsets) in the blood of COVID-19 patients that could potentially be used as predictors or risk factors of progression from mild to severe forms of the disease. 
 
Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, "Our study integrates frequencies of non-classical monocytes and immature neutrophils with calprotectin plasma levels as robust biomarkers of COVID-19 severity and suggests potential therapeutic strategies targeting calprotectin to alleviate severe COVID-19.”

These 7 SIgN researchers are recognized for their scientific excellence, contributions and influence in their fields through the publication of multiple highly cited papers during the last decade. Heartiest congratulations them!

Dr Chen Jinmiao
Dr Florent Ginhoux (5th consecutive time since 2016)
Dr Ng Lai Guan
Dr Subhra Biswas (2nd consecutive time since 2019)
Dr Anis Larbi (alumni)
Dr Andreas Schlitzer (alumni and 2nd consecutive time since 2019)
Dr Peter See (alumni)

11 September 2020

A team of researchers at A*STAR’s Singapore Immunology Network (SIgN), led by Senior Principal Investigator Wang Cheng-I, has made a tremendous breakthrough in identifying antibodies that block the SARS-CoV-2 virus from entering human cells, thus thwarting the symptoms of COVID-19. The team recently established a partnership with Japanese pharmaceutical company Chugai Pharmabody Research and is currently working at full tilt to bring these antibody candidate drugs to the clinic.

Reported in: Medical Xpress

8 September 2020

A collaborative study among medical professionals and scientists from the National Centre for Infectious Diseases (NCID) and A*STAR’s Singapore Immunology Network (SIgN) unveiled four crucial epitopes on the crown of the SARS-CoV-2 virus to which patient-derived antibodies can bind. Discoveries from two cooperative studies by scientists and medical professionals have been published in Nature Communications and EBioMedicine. The researchers found that patient-derived antibodies can accurately detect these four epitopes – S14P5, S21P2, S20P2 and N4P5 – located on spike proteins of the SARS-CoV-2 virus’ characteristic crown. N4P5 in particular, demonstrated the greatest specificity and sensitivity (100% and >96% respectively) against the SARS-CoV-2 virus.

Reported in: Asia Biotech

24 August 2020

Singapore scientists from A*STAR’s Singapore Immunology Network (SIgN), the National Centre for Infectious Diseases (NCID) and Duke-NUS Medical School have discovered a new variant of the COVID-19 virus that causes milder infections. The study was published in The Lancet medical journal and showed that COVID-19 patients infected with this new variant of SARS-CoV-2 had better clinical outcomes.

The variant, which likely came from Wuhan, China, was detected in a cluster of infections that occurred from January to March 2020. The variant has a large deletion that removes the ORF8 gene. In Singapore, the virus was transmitted from person-to-person across several clusters before being contained. The findings could have implications on the development of treatments and vaccines.

Reported in: Medical Xpress

21 August 2020

Singapore scientists from A*STAR’s Singapore Immunology Network (SIgN), the National Centre for Infectious Diseases (NCID) and Duke-NUS Medical School have discovered a new variant of the COVID-19 virus that causes milder infections. The study was published in The Lancet medical journal and showed that COVID-19 patients infected with this new variant of SARS-CoV-2 had better clinical outcomes.

The variant, which likely came from Wuhan, China, was detected in a cluster of infections that occurred from January to March 2020. The variant has a large deletion that removes the ORF8 gene. In Singapore, the virus was transmitted from person-to-person across several clusters before being contained. The findings could have implications on the development of treatments and vaccines.

Reported in: Reuters

19 August 2020

AUM Biosciences (AUM), a Singapore-headquartered clinical-stage biopharmaceutical company aiming to democratise R&D with a focus on discovering, acquiring, and developing novel therapeutics in oncology, has announced that together with A*STAR’s Singapore Immunology Network (SIgN), a new joint lab will be established in Singapore, centered on drug development and immuno-monitoring of novel oncology drugs. Housed in SIgN’s premises at Biopolis, Singapore’s biomedical research hub, the joint lab will focus on the discovery of novel and proprietary immune biomarkers and underlying drug mechanisms of action that will be used to better inform clinical trial design and study endpoint analysis. Combining SIgN’s scientific expertise in translational immunology, preclinical, and computational research with AUM’s extensive capabilities in clinical trial design and management will lead to better targeted development programmes for AUM’s cancer therapies.

Reported in: Bio Spectrum

18 July 2020

Researchers in Singapore have discovered the specific sites on the novel coronavirus that trigger the body to produce antibodies that can prevent further COVID-19 infection. These findings by scientists from the National Centre for Infectious Diseases (NCID) and the Agency for Science, Technology and Research (A*STAR) demonstrated that antibodies produced during infection attach to many parts of the virus, but only some antibodies are capable of eliminating the virus or offering protection against infection. Whether the antibodies produced are able to counteract the virus after attaching to its surface depends on where exactly they attach, the agencies said. The specific sites are called epitopes.

Professor Lisa Ng, Senior Principal Investigator at A*STAR’s Singapore Immunology Network, said that “the identification of these specific targets on the virus is a crucial advance in the development of better diagnostics and treatments for COVID-19. There is also potential to use these targets against similar coronaviruses to address other viral outbreaks.”

Reported in: Channel News Asia

6 June 2020

An op-ed by Dr Benjamin Seet, group chief research officer for the National Healthcare Group, and Professor Laurent Renia, executive director of A*STAR’s Singapore Immunology Network (SIgN), points out that the race for the Covid-19 vaccine has been elevated to the global stage. We are now witnesses to an interplay between science, biotechnology, public health, markets, governments and civil society. It remains to be seen how the pandemic will evolve, and what role a vaccine will eventually play in bringing it to an end.

Reported in: The Straits Times

28 May 2020

A team of scientists and researchers from A*STAR's Singapore A team of scientists and researchers from A*STAR's Singapore Immunology Network (SIgN) and Jinan University, Guangzhou, have deciphered human embryonic immune cell development and discovered how the earliest macrophages in humans stem from a distinct embryonic source and not the bone marrow. The study was co-led by Senior Principal Investigator Dr Florent Ginhoux from SIgN, as well as Prof Lan Yu and Prof Bing Liu from Jinan University.

Reported in: Asia Research News

23 May 2020

A number of Singapore groups have joined the international race to develop monoclonal antibodies against COVID-19. Monoclonal antibodies are immune system proteins that are created in the laboratory. Those include local biotech company Tychan, as well as a partnership between A*STAR’s Singapore Immunology Network (SIgN) and pharmaceutical company Chugai. Monoclonal antibodies can be specially designed and engineered to target the SARS-CoV-2 virus.

Reported in: The Straits Times

19 May 2020

Researchers at Singapore's Agency for Science, Technology and Research (A*STAR) have discovered an antibody that targets a specific part of the coronavirus, preventing it from infecting human cells, and are moving to develop it to defend against the COVID-19 disease. Dr Wang Cheng-I, senior principal investigator at A*STAR's Singapore Immunology Network (SIgN), said that his team discovered the antibody in mid-March, finding it in a collection of 30 billion human antibodies made by recombinant DNA technology. They confirmed its ability to prevent infection early last month. A*STAR is working on optimising the therapeutic antibody together with Japanese pharmaceutical company Chugai Pharmabody Research, with the aim of engineering it for clinical use. Dr Wang said the two organisations have a history of collaborating on antibody research, including on projects related to dengue.

Reported in: The Straits Times

15 May 2020

A*STAR is collaborating with Chugai Pharmabody Research, a research centre of the Chugai Group in Singapore, on joint research on a therapeutic antibody to fight COVID-19. The project focuses on a potential therapeutic antibody that was discovered by a research team at A*STAR’s Singapore Immunology Network (SIgN), led by Senior Principal Investigator Dr Wang Cheng-I. Professor Sir David Lane, Chief Scientist of A*STAR and Chairman of Chugai Pharmabody Research, explained more about antibodies and their role in treating COVID-19. He shared how the team hopes to develop the antibody that can neutralise the virus, into a medicine that can be given to people. It would potentially be able to treat COVID-19 patients, and even protect those without the disease.

14 May 2020

Dr Lisa Ng, senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN), and a leading infectious disease expert on infection and immunity, shares how her team’s prior experience has helped them quickly understand the nature of SARS-CoV-2, the virus that causes COVID-19. To provide the global scientific community with a roadmap to plan its next steps, she and her team has published their research findings in Nature Reviews Immunology.

Reported in: Medical Xpress

14 May 2020

The article shares how scientists - the detectives of the microbial world - are still learning more about the virus which causes COVID-19, so that tests, drugs and vaccines can be developed to identify and treat those who are infected, and inoculate those who are not.

Viruses are prone to mutations, so Dr Sebastian Maurer-Stroh, deputy executive director for research at A*STAR’s Bioinformatics Institute (BII) is involved in surveillance of the viral genome. He said that the mutations in the coronavirus so far have made little difference in its ability to infect humans.

Scientists are also discovering how the virus can cause disease in the human body and invade human cells. Dr Poh Chek Meng, research fellow at A*STAR's Singapore Immunology Network (SIgN), shared how the SARS-CoV-2 virus could invade lung cells and cause great damage in people who have compromised immune systems, and how the immune system itself could sometimes cause damage too.  Dr Matthew Tay, also a research fellow at A*STAR's SIgN added that an immune system element called cytokines instruct the body's immune 'soldiers' to come to the area and search for pathogens to eliminate.

One of the tools that humanity can use to fight the virus is antibody therapy. Chugai Pharmabody Research Pte. Ltd. (CPR), a research center of the Chugai Group in Singapore, joint research with A*STAR on a therapeutic antibody to fight COVID-19. This antibody targets the S-protein of the virus, preventing it from attaching onto a human host cell.

Reported in: The Straits Times

8 May 2020

Chugai Pharmabody Research Pte. Ltd. (CPR), a research center of the Chugai Group in Singapore, has begun joint research on a therapeutic antibody to fight COVID-19, with the Agency for Science, Technology and Research (A*STAR) in Singapore. This joint research project focuses on a potential therapeutic antibody for COVID-19 that was discovered by a research team led by Senior Principal Investigator Dr Cheng-I Wang at A*STAR’s Singapore Immunology Network (SIgN). Lead candidates were isolated from a high diversity synthetic human antibody library and showed high potency in neutralising live coronavirus which causes COVID-19.

Reported in: Bio Spectrum, Chugai Pharm

4 May 2020

Professor Lisa Ng, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN), outlines different detection methods for viruses such as SARS-CoV-2, including PCR and immunoassays that detect antibodies from individuals. She shares about considerations in the development of such detection methods, and how the results will help to shed light on the epidemiology of novel diseases like COVID-19.

Watch from: Frontiers, Youtube

30 April 2020

The COVID-19 research workgroup, chaired by National Centre for Infectious Diseases (NCID) executive director Leo Yee Sin, commissioned three studies that were released yesterday. The Health Ministry's chief health scientist, Professor Tan Chorh Chuan, is its adviser. The workgroup comprises 18 members from the ministry, public healthcare institutions, the Agency for Science, Technology and Research (A*STAR), and DSO National Laboratories. Among the workgroup are Professors Laurent Renia and Lisa Ng from SIgN, and Dr Sebastian Maurer-Stroh from BII.

Reported in: The Straits Times

6 April 2020

A team of Singapore scientists have found that patients with Covid-19 could have a dynamic and fluctuating immune response to the virus, particularly in the early stages of the disease. The finding is important as it could pave the way for research into existing or new drugs that could help prevent harmful immune reactions that may worsen the disease, said Dr Eugenia Ong, a member of the team and senior research fellow at Duke-NUS’ Emerging Infectious Diseases programme. "The study of very early stages of infection is interesting, and could lead to opportunities for early interventions. Potentially, some clinically approved drugs could be used to target certain inflammatory pathways to control virus-induced inflammation," said Professor Lisa Ng, senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN).

Reported in: The Straits Times, Asia One Online

11 March 2020

Fluidigm Corporation today announced the establishment of a new Center of Excellence (CoE) for Imaging Mass Cytometry™ (IMC™) in Singapore together with A*STAR’s Singapore Immunology Network (SIgN). The center will focus on single-cell deep spatial immunoprofiling to demonstrate the utility of highly multiplexed imaging across a range of disease areas such as cancer immunology. IMC, based on CyTOF® technology, is revolutionizing translational and clinical research by providing unprecedented visualization of complex cellular phenotypes and their relationships in the context of cancer, immuno-oncology, and immune-mediated diseases.

Reported in: Yahoo Online, Bio World, Market Screener, Globe Newswire

25 February 2020

Professor Lisa Ng, senior principal investigator of A*STAR’s Singapore Immunology Network (SIgN), said Sars had served as a “wake-up call” for the Lion City. “For Singapore, the Sars experience was a wake-up call about how diseases know no borders...” But from there, government agencies learned that maintaining a strong working relationship between scientists and the public health community was key, Ng said, adding that this dynamic has been “instrumental” in containing the current outbreak. Dr Sebastian Maurer-Stroh, deputy executive director of A*STAR’s Bioinformatics Institute (BII), said, “There is a good interplay between agencies, as the complementary puzzle pieces create the big picture needed to deal with complexities of an outbreak,” he added. “Coordination is also key and Singapore has just the critical size – not too big and not too small – where this can be done efficiently.”

Reported in: South China Morning Post

18 February 2020

Scientists from A*STAR’s Singapore Immunology Network (SIgN) have discovered that malaria parasites can sense a molecule produced by approaching immune cells and then use it to protect themselves from destruction. The new findings were published in eLife. The study reveals a previously unknown reversible mechanism that malaria uses to evade the immune system, paving the way towards new antimalarial drugs.

Reported in: Science Daily, Medical Xpress, Eureka Alert, Asia Research News

16 February 2020

Scientists around the world are looking to develop a cure for Covid-19. Experts from the Agency for Science, Technology and Research (A*STAR) and Tan Tock Seng Hospital have developed a diagnostic test kit that has been rolled out at a number of public hospitals in Singapore and also delivered to China. Professor Lisa Ng, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN) studies how the virus works and how the human body reacts to it, by analysing samples from patients in Singapore, and by working closely with clinicians and healthcare workers who interact directly with patients.

Reported in: The Straits Times

5 February 2020

Scientists are trying understand the genome of the coronavirus which originated in Wuhan, China. For patients infected with the coronavirus, additional proteins could lead to an inflammation of the lung tissue and cause pneumonia-like symptoms. Professor Lisa Ng, a senior principal investigator at A*STAR’s Singapore Immunology Network (SIgN) said that the infection with viruses sometimes cause exuberant immune responses known as 'cytokine storms'. This means excessive levels of pro-inflammatory cytokines will be produced.

Reported in: The Straits Times