Vincent Chi-Hang Lui

The University of Hong Kong | HKU · Department of Surgery

Background: Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients. Methods: Liver organoids (n = 51) were generated from liver...

Introduction: Laparoscopic inguinal hernia repair is a commonly performed procedure in children. Currently, monofilament polypropylene and braided silk are the two most frequently used materials. Studies have suggested more tissue inflammatory reactions with the use of multifilament non-absorbable sutures. However, little is known about the effect...

Organoids as three-dimension (3D) cellular organizations partially mimic the physiological functions and micro-architecture of native tissues and organs, holding great potential for clinical applications. Advances in the identification of essential factors including physical cues and biochemical signals for controlling organoid development have con...

Background Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with h...

The sequential occurrence of three layers of smooth muscle layers (SML) in human embryos and fetus is not known. Here, we investigated the process of gut SML development in human embryos and fetuses and compared the morphology of SML in fetuses and neonates. The H&E, Masson trichrome staining, and Immunohistochemistry were conducted on 6–12 gestati...

Biliary atresia (BA) is a disease in which the intra- and extrahepatic bile ducts are blocked, leading to cholestatic liver cirrhosis and liver failure. Kasai portoenterostomy (KPE) and liver transplantation are the gold treatment methods since effective medical interventions are lacking. Limited by the availability of early screening methods, chil...

Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, “pancreaticobiliary maljunction” and “congenital stenosis of bile ducts” proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is st...

Biliary atresia is a severe obliterative cholangiopathy in early infancy that is by far the most common cause of surgical jaundice and the most common indicator for liver transplantation in children. With the advanced knowledge gained from different clinical trials and the development of research models, a more precise clinical classification of BA...

Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism b...

Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured wit...

Genome engineering assumes an urgent part in quality guidelines. The utilization of high-throughput techniques for chromatin profiling and 3-D association planning gives rich exploratory informational collections depicting genome association and elements. This information challenge improvement of new models and calculations associating genome desig...

Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of liver development with a focus on cholangiocyte differentiation and how use of technical platforms, including rodent, zebrafish and organoid models, advances our understanding of Biliar...

Background Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic contribution, especially for nonsyndromic BA (common form: > 85%) remains poorly defined. Methods We conducted whole exome sequencing on 89 nonsyndrom...

Because of creative example planning and sequencing advances, quality articulation in singular cells would now be able to be estimated for a huge number of cells in a solitary trial. Since its presentation, single-cell RNA sequencing (scRNA-seq) approaches have reformed the genomics field as they set out exceptional open doors for settling cell het...

Hirschsprung is a birth defect of Enteric Nervous System (ENS) which is characterized by the absence of enteric neurons along the length of intestine. Hirschsprung is one of the complex diseases which has become a important topic of human genetics. In this article we have focused on RET gene mutation that is most common cause of HSCR disease. Out o...

The rapid development of next generation sequencing (NGS) tool and technologies over the past few years, valuable insights have been gained into the complex and diverse biological systems with diverse range from microbial communities to cancerous genome. The NGS base technologies based of genomics, epigenomics and transcriptomics, are preoperationa...

The relationship of epigenetic processes and the intestinal microbiota may serve as an essential role in elevating the bisulfite sequencing potentials in discovering host-microbiota interactions in germfree (GF) and conventional mice. The previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial...

To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and qual...

Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6–10 gestat...

Biliary atresia (BA) is an immune related disorder and STAT3 is a key signalling molecule in inflammation. This study was designed to clarify the function of STAT3 in BA. STAT3 expression was examined in patients and a mouse BA model in which STAT3 levels were further altered with a specific inhibitor or activator. Neutrophil accumulation and the l...

Objectives To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). Methods We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literatures reporting BA biomarkers published before August, 2020. Biomarkers sel...

Background: Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, patients with severe liver disease have been shown to have higher mortality. Overall, the me...

Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during ear...

Background and Aims Biliary atresia (BA) is a poorly understood deadly liver disease, often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aim to investigate the underlying pathomechanisms and molecular signatures associated with BA. Methods We combine organoid and transcriptomic analysis to gain new...

Purpose Biliary atresia (BA) is a devastating obstructive bile duct disease of newborns. BA has the highest incidence in Asians (1/5000), and its pathogenesis is unclear. We identified BA-private rare copy number variants (CNVs; 22 duplications and 6 deletions). ILF2 gene locates in the chromosome region (Chr1:153410347–153,634,058) which was delet...

Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic contribution remains poorly defined. We conducted exome sequencing on 89 nonsyndromic BA trios. In 31.5% of the patients, rare and deleterious de novo, homozygous...

Burn injury is common, and antimicrobial agents are often applied immediately to prevent wound infection and excessive inflammatory response. Although inflammation is essential for clearing bacteria and creating an environment conducive to the healing process, it is unclear what time-frame inflammation should be present for optimal wound healing. T...

In mammals, urorectal development starts at early embryonic stage, defective urorectal development results in anorectal malformations, which are common congenital developmental defects of the anus and the urethra in newborns. The etiology and embryology of the defects are still largely unknown. Platelet-derived growth factor receptor alpha (Pdgfra)...

Activation of innate immunity together with cholangiocyte damage occurs in biliary atresia (BA). However, detailed information on the inflammatory cells involved is lacking. This study investigates both the pathophysiology of CD11b+Gr-1+ cells in a mouse model of BA and their presence in BA patients. CD11b+Gr-1+ cells were targeted by an anti-Ly6G...

AIM To analyze the expression and function of the Notch signaling target gene Hes1 in a rhesus rotavirus-induced mouse biliary atresia model. METHODS The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathw...

The cloaca is an embryonic cavity that is divided into the urogenital sinus and rectum upon differentiation of the cloacal epithelium triggered by tissue-specific transcription factors including CDX2. Defective differentiation leads to persistent cloaca in humans (PC), a phenotype recapitulated in Cdx2 mutant mice. PC is linked to hypo/hyper-vitami...

Background Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a co...

Conditional deletion of Pdgfra at E7.5 resulted in phenotypic abnormalities and embryonic lethality in mutant embryos. E14.5 mutant embryos (CKO, PdgfraCre/ERT;Pdgfrafl/fl) were generally smaller, and displayed cleft face, bleeding, subepidermal bleb (arrowhead). Control littermate (Ctrl, Pdgfrafl/fl) was shown for comparison. (TIF)

Immuno-histochemistry for PDGFRA in CKO mutants. Conditional knockout (CKO, PdgfraCre/ERT;Pdgfrafl/fl) and control (Ctrl, Pdgfrafl/fl) embryos were collected at E12.5 of E9.5 Tm group for immunostaining for PDGFRA. Upper panel, immuno-reactivity for PDGFRA (brown) were localized in the mesenchyme tissues at the fourth ventricle (A), the developing...

PCR genotyping of mice for Cre, wild-type and floxed Pdgfra and Sry. (A) The wild-type Pdgfra, the floxed Pdgfra locus and the PdgfraCre/ERT locus were shown. Black boxes represent exons; ATG indicates the start of translation. The floxed allele contains the Neo cassette (gray box) and the two loxP sites (black arrowheads). Primers for PCR amplific...

Deletion of Pdgfra induced apoptosis. Sagittal sections of CKO (A, PdgfraCre/ERT;Pdgfrafl/fl) and control (B, Ctrl, Pdgfrafl/fl) E14.5 embryos of E11.5 Tm group were examined by TUNEL assay (Red). Highlighted regions were magnified and shown on the right. Number of embryos analyzed for each group was indicated as “n”, and representative photo of ea...

Rib cage anomalies of conditional Pdgfra knockout embryos. Skeletal staining of the rib cages of conditional Pdgfra knockout (CKO, PdgfraCre/ERT;Pdgfrafl/fl) (A-B) and control (Ctrl, Pdgfrafl/fl) (C) embryos of E10.5 Tm group were shown for comparison. The ribs were numbered and arrows indicated the respective location of the manubrium. Abbreviatio...

Primers and PCR conditions for the detection of the Cre, wild-type and floxed Pdgfra and Sry. (DOCX)

Background Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitt...

Biliary atresia (BA) is a neonatal biliary system disease closely associated with viral infection and bile duct inflammation. Silver nanoparticles (AgNps) have previously revealed antiviral and anti-inflammatory properties. In this study, we have investigated the effects of AgNps in the treatment of the Rhesus rotavirus inoculation induced BA in mi...

Unlabelled: The potential use of osteo-conducive biomaterials in the promotion of bone fracture healing has attracted wide attention. This study investigated if silver nanoparticles (AgNps) could promote the proliferation and osteogenesis of mesenchymal stem cells (MSCs), and improve bone fracture healing. We showed that AgNps promoted MSCs' proli...

To investigate the role of IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) in the development of enteric nervous system (ENS) and Hirschsprung disease (HSCR). In this study, we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos. The phenoty...

The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor-associated macrophages (TAMs) may promote disease progression with tumor specific manner. Here we report that in pediatric malignant soft-tissue tumors, the presence of TAMs and expression of adiponectin (APN) are heter...

Neural crest cells (NC) are a group of multipotent stem cells uniquely present in vertebrates. They are destined to form various organs according to their anterior-posterior (A-P) levels of origin in the neural tube (NT). They develop into a wide spectrum of cell lineages under the influence of signaling cascades, neural plate border genes and NC s...

By using NGS technologies, rapid advances in cancer genomics to uncover diverse microbial communities have been uncovered. NGS-based technologies for genomics, transcriptomics, and epigenetics are increasingly used to identify individual cells. Researchers will be able to uncover new and potentially unexpected biological discoveries by analyzing si...

Patterning of neural crest (NC) for the formation of specific structures along the anterio-posterior (A-P) body axis is governed by a combinatorial action of Hox genes, which are expressed in the neuroepithelium at the time of NC induction. Hoxb5 was expressed in NC at both induction and migratory stages, and our previous data suggested that Hoxb5...

RET gene is crucial for the development of enteric nervous system, and dys-regulation of RET expression causes Hirschsprung disease. HOXB5 regulates RET transcription, and perturbations in transcriptional regulation by HOXB5 caused reduced RET expression and defective enteric nervous system development in mice. The mechanisms by which HOXB5 regulat...

Neural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This stud...

Anorectal malformations (ARMs) are birth defects that require surgery and carry significant chronic morbidity. Our earlier genome-wide copy number variation (CNV) study had provided a wealth of candidate loci. To find out whether these candidate loci are related to important developmental pathways, we have performed an extensive literature search c...

Biliary atresia (BA) is a rare and most severe cholestatic disease in neonates, but the pathogenic mechanisms are unknown. Through a previous genome-wide-association-study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 gene, which was replicated in Chinese and Thai populations. This study aims t...

Inadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-β has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, whic...

Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined. Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6) and the graft rejection was monitored. In adiponectin-null mice we observ...

Immunohistochemical analysis of cardiac transplantation grafts. Sections were stained with Hematoxylin and Eosin (HE), rat anti-mouse CD4 and CD8 antibodies and bm12 to B6 grafts are compared to bm12 to APM−/− grafts. The samples were obtained from the grafts which the heart beating was stopped. (TIF)

Expression of AdipoR1 and AdipoR2 on T cells isolated from spleen of B6 and Apn−/− mice. The T cells were isolated with Dynal® CD4 Negative Isolation Kit and total RNA was extracted. The mRNA expression levels were determined by quantitative Q-PCR. (TIF)

The primers used in Quantitative real-time PCR (Q-PCR). The primers were synthesized by Invitrogen Hong Kong Ltd. (DOC)

Serum levels of IFN-γ and IL-2 at 7 days post-operatively in mice following skin grafting. n = 6 in each group (†p<0.01 compared to B6 to B6; ††p<0.001 compared to Apn−/− to Apn−/−; ‡‡p<0.01 compared to B6 to B6 and ‡p<0.05 compared to Apn−/− to Apn−/−). (DOC)

Mixed lymphocytes reaction (MLR). A Bone marrow derived dendritic cells from bm12 as the stimulator cells and T cells isolated from spleen of B6 or Apn−/− mice as the responder cells. The cells were mixed at different ratios and proliferation was measured with 3H-thymidine incorporation. B and C The maturation of dendritic cells from bm12 or B/c. B...

Immunohistochemical analysis of cellular infiltration. The tissue sections were stained with rat anti-mouse F4/80, rat anti-mouse CD4 and CD8 antibodies to illustrate the containing of macrophages, CD4+ and CD8+ cells in skin transplantation with bm12 as the donor to B6 or Apn−/− as the recipients. (TIF)

A Determination of serum FBS concentration used in MLRs containing splenocytes. B and C Effect of Compound C and SB203580 treatment on splenocyte apoptosis using Annexin V staining. (TIF)

(DOC)

Expression the cytokines mRNA in grafts. Th1, Th17, co-stimulatory molecule PD-L1, APN and its receptors in grafts of bm12 as donor and B6 or Apn−/− as recipient by Q-PCR were analyzed. One sample was used in each B6 and Apn−/− group. (TIF)

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10,000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology...

Haplotypes harbouring NRG3 deletion for the 5 carriers of the discovery phase. (DOCX)

Box plot of intensity variation parameters for Birdsuite. (A) copy number (CN) estimate and (B) variation in intensity per chromosome. (TIF)

Schematic diagram defining the consensus CNV segments. Green and red boxes denote the segments called by Birdseye and PennCNV respectively while consensus CNV was represented by grey shaded box. (TIF)

Violin plot of CNV rate and gene count for HSCR cases and controls. Shaded regions of the violin plots represent the frequency distribution of CNV rate (upper panel) and gene count (lower panel) for (A,D) all CNVs, (B,E) rare and (C,F) common CNVs. The box in the middle resembles the standard box plot, depicting the lower quartile, median and upper...

Summary of sample origin for the discovery and replication phase (DOCX)

Genome-wide copy number analysis uncovers a new HSCR gene: NRG3. (DOCX)

Functional characteristics at NRG3 deletion. Enhancer regions implicated by strong signals of chromatin modification H3K4me1 and DNaseI hypersensitivity were shown using corresponding ENCODE tracks in the UCSC genome browser (hg18). (TIF)

Detection of the NRG3 deletion breakpoints. Semi-quantitative PCR reactions (Pr1 to Pr8) designed across a 27 kb region spanning the predicted NRG3 deletion (red vertical stripes on white background) and boundary regions (upstream: green background; downstream: purple background). Pr 4 primer pair was specifically designed within the deletion and u...

List of rare, HSCR-specific genic CNVs. (XLS)

SNP information of IBS segment shared by 5 HSCR patients with NRG3 deletions corresponding to Table S7. (DOCX)

Primers and PCR conditions used in the detection of the deletion breakpoint. (DOCX)

Box plot of intensity variation parameters for PennCNV. (A) log R ratio variation (LRR SD); (B) BAF drift; (C) median absolute deviation (MAD) and (D) wave factor. Statistical significance between cases and controls was assessed by rank sum test. (TIF)

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recomb...

Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 12...