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Mothership interviewed Professor Ren Ee Chee, Principal Investigator at A*STAR’s �����Immunology Network (SIgN), about taking the vaccine booster jab for COVID-19.

Prof Ren explained that the booster shot will strengthen immunity even further, better protecting the person against infection and severe illness. He noted that there is a possibility of requiring regular shots, similar to how we manage the seasonal flu, adding that while watching how the Covid-19 virus mutates and evolves, it is important to continue observing the Safe Management Measures and exercise social responsibility. These good practices, coupled with vaccination and the availability of anti-viral drugs, can help reduce the spread, he said.

Regarding the safety and efficacy of mixing vaccines, Prof Ren said that there is a range of vaccines available that appear to have no adverse effects and were recommended by an MOH expert committee.

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have developed new, more accurate preclinical models of advanced human gastric cancer development and spread. Using these models, they have identified Lgr5-expressing tumour cells as the cancer stem cells responsible for driving gastric cancer growth and spread.

The research was led by IMCB in collaboration with researchers from A*STAR’s �����Immunology Network and Genome Institute of Singapore, as well as the Cancer Research Institute of Kanazawa University, Duke-NUS Medical School, National University Health System, and Cancer Science Institute of �����at NUS.

“It's a breakthrough for us to apply our new models of advanced human gastric cancer to identify the specific cells – Lgr5-expressing tumour cells – involved in cancer progression. The discovery of these cells is invaluable for understanding the spread and development of gastric cancers, as well as informing the development of more effective treatments in future,” said Professor Nick Barker, Research Director at A*STAR’s IMCB and lead researcher of the study.

Labcorp, an American life sciences company, has launched a new laboratory in �����and is planning to expand its headcount by 25 per cent. The company recently inked research collaborations with the �����Immunology Network and the Diagnostics Development Hub under the Agency of Science, Technology and Research (A*STAR).
 
Labcorp’s new bioanalytical lab facility is an expansion of its central laboratory services here and will help to expand the capabilities of Singapore’s biomedical ecosystem, particularly providing bioanalytical testing services that are critical to early-stage development of biologics and vaccines in Singapore.

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: /Research/our-people/hcr

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

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

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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 �����Immunology Network (SIgN), in collaboration with the Skin Research Institute of �����(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.

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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 �����Immunology Network at the �����, 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."

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A*STAR’s Infectious Disease Laboratory (ID Labs) and �����Immunology Network (SIgN), together with National University of �����and Duke-National University School of Medicine, is supporting the first long-term study titled "�����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 �����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.

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Dr. Florent Ginhoux from A*STAR's �����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.

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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 �����, 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 �����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.

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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 �����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 �����, 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 �����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."

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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, �����, Technology and Research’s (A*STAR) �����Immunology Network (SIgN), and the National Centre of Infectious Diseases, �����(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.

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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 �����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 �����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: , , Berita Harian,

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 �����Science and Technology Research Council, KK Women's and Children's Hospital and Duke-National University of �����School of Medicine.

Dr Florent Ginhoux, senior principal investigator at A*STAR’s �����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.

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Clinicians and scientists from �����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 �����, Technology and Research (A*STAR) including the �����Immunology Network (SIgN) and the Genome Institute of �����(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 �����, 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 �����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, �����– Dr Florent Ginhoux, Dr Ng Lai Guan, and Dr Melissa Ng from A*STAR’s �����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:

�����kicked off its COVID-19 vaccinations for seniors aged 70 and above last week. Professor Lam Kong Peng, executive director of the �����Immunology Network (SIgN) under the �����, 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 �����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.