A5083974241- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- interferon and immune responses
- Cancer-related molecular mechanisms research
- 14-3-3 protein interactions
- Genomics and Phylogenetic Studies
- T-cell and Retrovirus Studies
- Neuroblastoma Research and Treatments
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Wildlife Ecology and Conservation
- Vector-Borne Animal Diseases
- Cancer-related gene regulation
- Biochemical and Molecular Research
- T-cell and B-cell Immunology
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Genomics and Chromatin Dynamics
- Viral-associated cancers and disorders
- Aquaculture disease management and microbiota
National University Cancer Institute, Singapore
2018-2024
National University of Singapore
2018-2024
University of Malaya
2014-2020
Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology evolution, we developed genome assemblies Malayan ( Manis javanica ) Chinese M. pentadactyla pangolins. Strikingly, found that interferon epsilon IFNE ), exclusively expressed in epithelial cells important skin mucosal immunity, is pseudogenized all African Asian species...
A heritable polymorphism within regulatory sequences of the LMO1 gene is associated with its elevated expression and increased susceptibility to develop neuroblastoma, but oncogenic pathways downstream transcriptional co-regulatory protein are unknown. Our ChIP-seq RNA-seq analyses reveal that a key directly regulated by MYCN ASCL1, which encodes basic helix-loop-helix transcription factor. Regulatory elements controlling ASCL1 bound LMO1, factors GATA3, HAND2, PHOX2B, TBX2 ISL1-all members...
Abstract Background Extranodal natural killer/T-cell lymphoma (NKTL) is an aggressive type of non-Hodgkin with dismal outcome. A better understanding disease biology and key oncogenic process necessary for the development targeted therapy. Super-enhancers (SEs) have been shown to drive pivotal oncogenes in various malignancies. However, landscape SEs SE-associated remain elusive NKTL. Methods We used Nano-ChIP-seq active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) profile...
The oral streptococci are spherical Gram-positive bacteria categorized under the phylum Firmicutes which among most common causative agents of bacterial infective endocarditis (IE) and also important in septicaemia neutropenic patients. Streptococcus mitis group is comprised 13 species including some human colonizers such as S. mitis, oralis, sanguinis gordonii well tigurinus, oligofermentans australis that have only recently been classified poorly understood at present. We present...
Abstract Multiple myeloma is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in multiple myeloma. Recently, essential oncogenic drivers a wide range of cancers have been shown to be controlled by super-enhancers (SE). We used chromatin immunoprecipitation sequencing the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) profile unique SEs t(4;14)-translocated chaperone HJURP...
Abstract Multiple myeloma (MM) is an aggressive plasma cell neoplasm characterized by genomic heterogeneity. Superenhancers (SEs) are defined as large clusters of enhancers in close proximity, which regulate genes for maintaining cellular identity and promote oncogenic transcription to cancer cells highly addicted. Here, we analyzed cis -regulatory elements MM samples with H3K27ac ChIP-seq, identify novel SE-associated involved the pathogenesis. SEs their associated cancerous tissue were...
Abstract Pangolins are scale-covered mammals, containing eight endangered species. Maintaining pangolins in captivity is a significant challenge, part because little known about their genetics. Here we provide the first large-scale sequencing of critically Manis javanica transcriptomes from different organs using Illumina HiSeq technology, yielding ~75 Giga bases and 89,754 unigenes. We found some unigenes involved insect hormone biosynthesis pathway also 747 lipids metabolism-related that...
Abstract The transcription factor MYB is a crucial regulator of hematopoietic stem and progenitor cells. However, the nature lineage-specific enhancer usage Myb gene largely unknown. We identify −68 enhancer, regulatory element which marks basophils mast Using activity, we show population granulocyte-macrophage progenitors with higher potential to differentiate into Single cell RNA-seq demonstrates differentiation trajectory continuous from mature in vivo, characterizes bone marrow cells...
IRF4 is a master regulator of immunity and also frequently overexpressed in mature lymphoid neoplasms. Here, we demonstrate the oncogenicity vivo, its potential effects on T-cell development clonal evolution using zebrafish model. IRF4-transgenic develop aggressive tumors with massive infiltration abnormal lymphocytes that spread to distal organs. Many late-stage are mono- or oligoclonal, tumor cells can expand recipient animals after transplantation, demonstrating their malignancy. Mutation...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy derived from thymic precursors. Approximately 40-60% of T-ALL cases exhibit aberrant overexpression the TAL1 oncogenic transcription factor. Here, we provide a comprehensive view TAL1-induced transcriptional program in human cells using rapid protein degradation system coupled with integrative approaches. Our study demonstrates that targets can be classified into several groups, each which exhibits unique gene expression...
Neuroblastoma originates from developing neural crest and can interconvert between the mesenchymal (MES) adrenergic (ADRN) states, each of which are controlled by different sets transcription factors forming core regulatory circuit (CRC). However, roles CRC in induction maintenance specific state poorly understood. Here, we demonstrate that overexpression ASCL1, an ADRN factor, MES neuroblastoma cells opens closed chromatin at promoters key genes, accompanied epigenetic activation...
Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate high-resolution contact map myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq HiChIP cell lines, patient-derived cells normal Our comprehensive transcriptomic phenomic analyses prioritize candidate genes with biological...
Synthetic glucocorticoids (GCs), such as dexamethasone and prednisone, remain key components of therapy for patients with lymphoid malignancies. For pediatric acute lymphoblastic leukemia (ALL), response to GCs remains the most reliable prognostic indicator; failure respond GC correlates poor event-free survival. To uncover resistance mechanisms, we performed a genome-wide, survival-based short hairpin RNA screen identified orphan nuclear receptor estrogen-related receptor-β (ESRRB) critical...
Aldehyde dehydrogenases (ALDHs) are overexpressed in various types of cancers. One the ALDH family genes, ALDH1A2, is aberrantly expressed more than 50% T-cell acute lymphoblastic leukemia (T-ALL) cases. However, its molecular function and role T-ALL pathogenesis largely unknown. ChIP-seq RNA-seq analyses showed that oncogenic transcription factor TAL1 regulatory partners bind to intronic element ALDH1A2 gene, directly inducing a T-ALL-specific isoform with enzymatic activity. was...
Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed genomes of two critically endangered Asian pangolin species, namely Malayan ( Manis javanica ) Chinese pentadactyla ). These complete genome sequences will serve as reference for future research to address issues species conservation advance knowledge in mammalian biology evolution. To further facilitate global effort biology, we developed Pangolin Genome Database (PGD), a hub hosting...
Mycobacterium brisbanense is a member of fortuitum third biovariant complex, which includes rapidly growing spp. that normally inhabit soil, dust and water, can sometimes cause respiratory tract infections in humans. We present the first whole-genome analysis M. UM_WWY was isolated from 70-year-old Malaysian patient. Molecular phylogenetic analyses confirmed identification this strain as showed it has an unusually large genome compared with related mycobacteria. The size (~7.7Mbp) consistent...
Paraburkholderia fungorum (P. fungorum) is a Gram-negative environmental species that has been commonly used as beneficial microorganism in agriculture an agent for biocontrol and bioremediation. Its use controversial many people believe it could harm human health; however, there no clear evidence to support.The pangolin P. (pangolin Pf) genome genomic size of approximately 7.7 Mbps with N50 69,666 bps. Our study showed Pf supported by from the core SNP-based phylogenetic analysis ANI...