Lui Chi Hang Vincent 呂志恒

  • Scholarship in 1989 at University of Hong Kong

Vincent Lui is a developmental molecular biologist.

 Research Interests:

  1. Stem cells / Organoids
  2. Molecular mechanisms controlling neural crest cells and enteric nervous system (ENS) development
  3. Genetics of neural crest cell associated developmental anomalies in human such as Hirschsprung's disease
  4. Hepatobiliary development and associated anomalies such as biliary atresia

Currently

Ongoing Projects:

My research focusses on the translation of basic science and advanced technology for a better understanding of disease mechanisms and clinical applications in the field of paediatric surgery, covering debilitating birth defects including Hirschsprung’s Disease, Anorectal Malformations and congenital pulmonary airway malformation affecting newborn babies.

Concurrently, I study another devastating condition, biliary atresia (BA), which causes obstruction of bile flow, resulting in persistent jaundice and eventual liver failure in babies. I have pioneered the use of liver organoids and RNA sequencing technology in the pathomechanism study of BA. Furthermore, I have also identified a novel BA diagnostic marker.

Using transgenic and knockout approaches, mouse mutants of developmental disorders have been generated. Impact of various signaling pathways in the normal and abnormal development of the enteric nervous system and in urorectal development have been investigated in these mutants.

Using human liver organoid culture and transgenic/knockout zebrafish models, we investigate the genes / signaling pathways in the developmental regulation of the bile duct development and in the pathogenesis of Biliary Atresia


Selected Publications:

  1. Fu M, Lui VCH, Sham MH, Pachnis V, Tam PKH. Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut. J Cell Biol 2004; 166(5): 673-684. 
  2. Lui VCH, Cheng WWC, Leon TYY, Lau DKC, Garcia-Barcelo MM, Miao XP, Kam MKM, So MT, Chen Y, Wall NA, Sham MH, Tam PKH. Perturbation of Hoxb5 signaling in vagal neural crest cells down-regulates Ret leading to intestinal hypoganglionosis in mice. Gastroenterology 2008 Apr; 134: 1104-1115.
  3. Garcia-Barcelo MM, Tang CS, Ngan ESW, Lui VCH, Chen Y, So MT, Leon TY, Miao XP, Shum CK, Liu FQ, Yeung MY, Yuan ZW, Guo WH, Liu L, Sun XB, Huang LM, Tou JF, Song YQ, Chan D, Cheung KM, Wong KK, Cherny SS, Sham PC, Tam PKH. Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease. Proc Natl Acad Sci U S A 2009 Feb 24; 106(8): 2694-2699. 
  4. Ngan, E.S.W., Garcia-Barcelo, M.M., Yip, B.H.K., Poon, P.C., Lau, C.S.T., Kwok, K.M., Sat, E.W.Y., Sham, M.H., Wong, K.K.Y., Wainwright, B.J., Cherny, S.S., Hui, C.C., Sham, P.C., Lui, V.C.H., Tam, P.K.H. (2011) Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung’s disease in mice and humans.  J Clin Invest. 2011 Sep 1;121(9):3467-78.
  5. Tang, C.S., Cheng, G., So, M.T., Yip, B.H.K., Miao, X.P., Wong, E.H.M., Ngan, E.S., Lui, V.C.H., Song, Y.Q., Chan, D., Cheung, K., Yuan, Z.W., Lei, L., Chung, H.Y., Liu, X.L., Wong, K.K.Y., Marshall, C.R., Scherer, S., Cherny, S.S., Sham, P.C., Tam, P.K.H., Garcia-Barceló, M.M. (2012) Genome-wide copy number analysis uncovers a new HSCR gene: NRG3. PLoS Genetics 2012;8(5):e1002687
  6. Cheng, G., Tang, C.S., Wong, E.H., Cheng, W.W., So, M.T., Miao, X., Zhang, R., Cui, L., Liu, X., Ngan, E.S., Lui, V.C., Chung, P.H., Chan, I.H., Liu, J., Zhong, W., Xia, H., Yu, J., Qiu, X., Wu, X.Z., Wang, B., Dong, X., Tou, J., Huang, L., Yi, B., Ren, H., Chan, E.K., Ye, K., O Reilly, P.F., Wong, K.K., Sham, P.C., Cherny, S.S., Tam, P.K., Garcia-Barceló, M.M. (2013) Common genetic variants regulating ADD3 gene expression alter biliary atresia risk. J Hepatol. 2013 Dec;59(6):1285-91. doi:pii: S0168-8278(13)00532-1. 10.1016/j.jhep.2013.07.021.

  7. Kam, M.K.M., Cheung, M.C.H., Zhu, J.J., Cheung, W.W.C., Sat, E.W.Y., Tam, P.K.H., Lui, V.C.H. (2014) Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice. Cell Death Differ. Feb;21(2):278-89. doi: 10.1038/cdd.2013.142.

  8. Ng, R.C.L., Matsumaru, D., Ho, A.S.H., Garcia-Barceló, M.M., Yuan, Z.W., Smith, D., Kodjabachian, L., Tam, P.K.H., Yamada, G., Lui, V.C.H. (2014) Dysregulation of Wnt Inhibitory Factor 1 (Wif1) expression resulted in aberrant Wnt-β-catenin signaling and cell death of the cloaca endoderm, and anorectal malformations. Cell Death Differ. Jun;21(6):978-89. doi: 10.1038/cdd.2014.20.

  9. Miyagawa, S., Harada, M., Matsumaru, D., Tanaka, K., Inoue, C., Nakahara, C., Haraguchi, R., Matsushita, S., Suzuki, S., Nakagata, N., Ng, R.C.L., Akita, K., Lui, V.C.H., Yamada G. (2014) Disruption of the Temporally Regulated Cloaca Endoderm β-catenin Signaling Causes Anorectal Malformations. Cell Death Differ. Jun;21(6):990-7. doi: 10.1038/cdd.2014.21.

  10. Zhang, R.Z., Lee, P.Y., Lui, V.C.H., Liu, X.L., To, M., Yeung, K.W.K., Wong, K.K.Y. (2015) Silver nanoparticles promote osteogenesis of mesenchymal stem cells and improve bone fracture healing in osteogenesis mechanism mouse model. Nanomedicine: Nanotechology, Biology and Medicine. Nov;11(8):1949-59. doi: 10.1016/j.nano.2015.07.016.

  11. Gui H, Schriemer D, Cheng WW, Chauhan RK, Antiňolo G, Berrios C, Bleda M, Brooks AS, Brouwer RW, Burns AJ, Cherny SS, Dopazo J, Eggen BJ, Griseri P, Jalloh B, Le TL, Lui VC, Luzón-Toro B, Matera I, Ngan ES, Pelet A, Ruiz-Ferrer M, Sham PC, Shepherd IT, So MT, Sribudiani Y, Tang CS, van den Hout MC, van der Linde HC, van Ham TJ, van IJcken WF, Verheij JB, Amiel J, Borrego S, Ceccherini I, Chakravarti A, Lyonnet S, Tam PK, Garcia-Barceló MM, Hofstra RM. (2017) Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes. Genome Biol. Mar 8;18(1):48. doi: 10.1186/s13059-017-1174-6.

  12. Hsu JSJ, So M, Tang CSM, Karim A, Porsch RM, Wong C, Yu M, Yeung F, Xia H, Zhang R, Cherny SS, Chung PHY, Wong KKY, Sham PC, Ngo ND, Li M, Tam PKH, Lui VCH, Garcia-Barcelo MM. (2018) De novo mutations in Caudal Type Homeo Box transcription Factor 2 (CDX2) in patients with persistent cloaca. Hum Mol Genet. Jan 15;27(2):351-358. doi: 10.1093/hmg/ddx406.

  13. Zhang R, Lin Z, Fu M, Guan X, Yu J, Zhong W, Zeng J, Lui VCH, Tam PKH, Lamb JR, Xia H, Chen Y. (2018) The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus-Induced Biliary Atresia. Am J Pathol. Nov;188(11):2617-2628. doi: 10.1016/j.ajpath.2018.07.024.

  14. Qian C, Wu ZL, Ng RCL, Garcia-Barceló MM, Yuan ZW, Wong KKY, Tam PKH, Lui VCH. (2019) Conditional deletion of platelet derived growth factor receptor alpha (Pdgfra) in urorectal mesenchyme causes mesenchyme apoptosis and urorectal developmental anomalies in mice. Cell Death Differ. Oct 15. doi: 10.1038/s41418-018-0216-2.

  15. Babu RO*, Lui VCH*, Chen Y*, Yiu RS, Ye Y, Niu B, Wu Z, Zhang R, Yu MON, Chung PHY, Wong KKY, Xia H, Zhang MQ, Wang B, Lendahl U, Tam PKH. (2020) Beta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia. J Hepatol. 73:1391–1403 (DOI: https://doi.org/10.1016/j.jhep.2020.06.012) (*, Co-first author)

  16. Lam WY, Tang CSM, So MT, Hsu JS, Chung PHY, Nicholls JM, Yeung F, Lee CWD, Ngo DN, Nguyen PAH, Mitchison HM, Jenkins D, O’Callaghan C, Garcia-Barceló MM, Lee SL, Sham PC, Lui VCH*, Tam PKH*. (2021) Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism. EBioMedicine Sep; 71:103530 (*, Co-corresponding authors)

  17. Lendahl U, Lui VCH, Chung PHY, Tam PKH. Biliary Atresia – emerging diagnostic and therapy opportunities. EBioMedicine. 2021 Dec; 74: 103689. Published online 2021 Nov 12. doi: 10.1016/j.ebiom.2021.103689. PMCID: PMC8604670.

  18.  Lui VCH*, Hui KPY*, Babu RO, Yue H, Chung PHY, Tam PKH, Chan MCW#, Wong KKY#. Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication. Sci Rep. 2022; 12: 5375. Published online 2022 Mar 30. doi: 10.1038/s41598-022-09306-6. PMCID: PMC8965546. (*, Co-first authors; #, Co-corresponding authors)

  19. Lyn H, Ye Y, Lui VCH, Wu W, Chung PHY, Wong KKY, Li H-W, Wong MS, Tam PKH*, Wang B*. Plasma amyloid-beta levels correlated with impaired hepatic functions: an adjuvant biomarker for the diagnosis of Biliary Atresia. Front. Surg., 05 September 2022. Sec. Pediatric Surgery. https://doi.org/10.3389/fsurg.2022.931637 (*, co-corresponding authors)