A5062050317- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Drug-Induced Adverse Reactions
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- Influenza Virus Research Studies
- RNA modifications and cancer
- Vaccine Coverage and Hesitancy
- RNA Research and Splicing
- Pharmaceutical studies and practices
- Viral-associated cancers and disorders
- Colorectal and Anal Carcinomas
- CAR-T cell therapy research
- Genomic variations and chromosomal abnormalities
- Aquaculture disease management and microbiota
- interferon and immune responses
- Viral Infections and Immunology Research
- Hematopoietic Stem Cell Transplantation
National University of Singapore
2012-2024
Singapore Immunology Network
2014-2024
Agency for Science, Technology and Research
2014-2024
A*STAR Graduate Academy
2022
University of Cambridge
2009
Genome Institute of Singapore
2003-2007
Karolinska Institutet
1982
SummaryBackgroundThe cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis various isolates might provide an indication potential strain differences this virus. Moreover, mutation will help to develop effective vaccines.MethodsWe sequenced the entire SARS viral cultured from index case (SIN2500) presenting in Singapore, three primary contacts (SIN2774, SIN2748, and SIN2677), one secondary contact (SIN2679). These sequences...
Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP-ribosylating enzyme essential for initiating various forms of DNA repair. Inhibiting its activity with small molecules thus achieves synthetic lethality by preventing unwanted repair in the treatment cancers. Through enzyme-dependent chromatin remodeling and enzyme-independent motif recognition, PARP1 also plays important roles regulating gene expression. Besides presenting current findings on how each process individually controlled PARP1, we...
The p53 tumour suppressor has an important role in cancer cells. Here we show that regulates expression of major histocompatibility complex I on the cell surface. We line HCT116, which lacks exhibits significantly lower than its wild-type counterpart. Using a combination chromatin immunoprecipitation sequencing and gene analysis, demonstrate upregulates endoplasmic reticulum aminopeptidase 1 by binding to cognate response element ERAP1 gene. Silencing decreases protein levels therefore...
Abstract Understanding the impact of age on vaccinations is essential for design and delivery vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis multiple compartments memory immune response in 312 individuals vaccinated with BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody T cell responses most individuals. However, recognition Spike protein Delta Omicron variants less efficient than that ancestral Wuhan strain. Age-stratified...
The tumor suppressor p53 is a master transcriptional regulator that affects diverse range of cellular events. Surprisingly, even with >100 validated response element (RE) sequences available, the effect binding on behavior seldom predictable and no functional rules have been described. Here, we report systematic study role specific nucleotides within p53RE by using p21, well-known target for activation contrasting it Lasp1, gene recently identified to be repressed p53. Functional assays...
Significance Killer cell immunoglobulin-like receptors (KIRs) function as key recognition elements in innate immunity. Structural information for inhibitory KIRs 2DL2, 2DL1, and 3DL1 complex with their respective HLA ligands is available, but such data activating are lacking. We report here the successful crystallization solved structure of KIR2DS2 HLA-A*11:01. The clearly explains role Tyr45, which has long puzzled KIR researchers because it differentiates from all KIRs, now shown to bind...
Waning antibody levels post-vaccination and the emergence of variants concern (VOCs) capable evading protective immunity have raised need for booster vaccinations. However, which combination coronavirus disease 2019 (COVID-19) vaccines offers strongest immune response against Omicron variant is unknown.
The severity of hepatocellular carcinoma (HCC) and the lack good diagnostic markers treatment strategies have rendered disease a major challenge. Previous microarray analyses HCC were restricted to selected tissue sample sets without validation on an independent series samples. We describe approach identification composite discriminator cassette by intersecting different datasets. studied global transcriptional profiles matched tumor nontumor liver samples from 37 patients using cDNA (cDNA)...
The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron has raised concerns on efficacy COVID-19 vaccines. Here, we examined waning antibody responses against different variants following primary booster vaccination. We found that were low response was almost non-existent. Efficient boosting all including Omicron, observed a third dose. tested significantly higher at one month vaccination, compared with two months for individuals, responders identified...
HLA‐B27 is strongly associated with ankylosing spondylitis (AS) but the role of HLA molecule itself still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 normals found that B*2706 allele has a significant negative association disease (p=0.047). Together recent data indicating existence “protective” alleles, our shows plays crucial in development.
Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related deaths globally. One cellular hallmarks this disease dysregulation apoptosis, and a better understanding process important if progress to be made toward effectively treating HCC. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) RNA-binding protein that implicated in apoptosis upregulated various cancers, including In study, we report new evidence for crucial role hnRNP suppressing HCC cells. We used...
Hepatocyte nuclear factor 4α (HNF4α) is a dimeric transcription that controls as much 60% of all liver genes. However, how it achieves such broad functional diversity unknown. Here, we show inflammation and immune pathway genes are differentially regulated in an isoform-dependent manner, confirming each isoform homodimer preferentially regulates subset HNF4α targets. With 12 human clones, tested combinatorial pairings to determine whether heterodimers functional. Indeed, synergistic potent...
Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial for protection against influenza A virus (IAV) infection. The CD8 cell response the M158-66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) molecule expressed approximately half of human population. Here we report that GILGFVFTL multiple HLA-C*08 alleles as well. We observed was able to elicit cytotoxic lymphocyte (CTL) responses in both...
Influenza A viruses (IAV) are among the most common pathogens to cause human respiratory infections. better understanding on interplay between IAV and host factors may provide clues for disease prevention control. While many known downregulate p53 upon entering cell in order reduce innate antiviral response, infection is unusual that it activates p53. However, has not been clear whether this process pro- or anti- viral effects. In study, using isogenic wildtype p53null A549 cells generated...
Tumour cells of undifferentiated nasopharyngeal carcinoma (NPC) consistently harbour Epstein–Barr virus (EBV) genes. Expression mRNA transcripts associated with EBV latency has been demonstrated in such cells. However, expression lytic genes not well elucidated, although various lines evidence have suggested that there is replication NPC tumour We studied representative by RT–PCR nasopharynx biopsies obtained from and control individuals. In both biopsies, BZLF1, BALF2 BCLF1 were detected...
The control of gene regulation within the major histocompatibility complex (MHC) remains poorly understood, despite several expression quantitative trait loci (eQTL) studies revealing an association MHC with independent tag-single nucleotide polymorphisms (SNPs). haplotype variation may exert a greater effect on phenotype than specific single variants. To explore sequence diversity phenotypes across MHC, we examined transcriptomic landscape at haplotype-specific resolution for three...
Liver specificity of hepatitis B virus (HBV) replication has been attributed to the action its second enhancer (EII). We report here characterization EII and subsequent isolation a novel liver-specific DNA-binding protein which binds activates EII. The cDNA clone protein, designated E2BP, was isolated from lambda gt11 expression library constructed hepatoma cell line HuH-6 screened with binding site probe derived Sequence analysis E2BP revealed 86.6% homology rat heterogeneous nuclear...