Dr Lui, Vincent Chi Hang 呂志恒
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.
After obtaining PhD degree from the University of Hong Kong, I joined the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands as postdoctoral fellow and started my research on developmental anomalies. I returned to Hong Kong and joined the Division of Paediatric Surgery, Department of Surgery, the University of Hong Kong at the end of 1998 as a Research Assistant professor, promoted to Assistant professor in 2001, and Associate Professor in 2009.
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
After obtaining PhD degree from the University of Hong Kong, I joined the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands as postdoctoral fellow and started my research on neural crest cells (NCCs) and its associated developmental anomalies. I returned to Hong Kong and joined the Division of Paediatric Surgery, Department of Surgery, the University of Hong Kong at the end of 1998 as a Research Assistant professor, promoted to Assistant professor in 2001, and Associate Professor in 2009. Main research focuses 1. Molecular mechanisms controlling neural crest cells (NCCs) and enteric nervous system (ENS) development 2. Genetics of NCC associated developmental anomalies in human such as Hirschsprung's disease (HSCR) 3. Neural Crest Stem cells biology The enteric nervous system (ENS), a part of the autonomic nervous system, directly controls the peristaltic and endocrine functions of the gut in vertebrates, and normal functioning ENS is required for life. Hirschsprung disease (HSCR, MIM142623) is a major neurodevelopmental disorder of the ENS, which is characterized by the absence/reduction of ganglion cells in the lower digestive tract in newborns. Patients develop constipation, diarrhea, and vomiting and sometimes lead to life-threatening colon complications, like enterocolitis and toxic megacolon. HSCR causes considerable mortality and morbidity. HSCR is a complex multifactorial disease, which most commonly presents sporadically although it can be familial (5-20% of cases). The disease displays high heritability, large sex bias (male:female; 4:1), high sibling recurrence risk, and non-Mendelian inheritance in families. HSCR is most often found among Asians (28 per 100,000 live births). My research focuses in several important signaling pathways in the ENS development including the RET-HOXB5-TTF-1; Prokinecticin-1-GDNF; and Hedgehog pathways. We investigate the role of a number of homeobox containing genes in the ENS development, in particular, the HOXB5. Multiple approaches are taken in my laboratory including (i) gene knockout in mice; (ii) transgenic mouse; (iii) ex vivo embryonic gut explant culture; and (iv) NCC stem cell culture. My group provides the first evidence that a patterning gene HOXB5 regulates trunk and vagal enteric NCC development and survival. Disruption of HOXB5 regulation leads to NCC disorders that resembles HSCR in human. To investigate HOXB5 in mature neurons, a neuron specific-cre mouse strain has been generated by our group, and this mouse strain (NSE-MerCreMer) will be very useful in the investigation of HOXB5 (or other gene) function in the specification and functional maintenance of subtypes of neurons in the digestive tract as well as in the central nervous system. We also developed a culture system for the isolation and culturing of enteric NCCs. We have employed this NCC culture successfully in the investigation of sonic hedgehog, GDNF and Prokinecticin-1 signalings in the development of NCC, and their implications in the pathogenesis of HSCR. I hope to develop and be able to apply NCCs as a stem cell replacement therapy for the treatment of HSCR and/or other NCC associated developmental anomalies.
|Awardees||Award Date||Honours / Awards / Prizes||Category|
|2007-10-01||The Outstanding Award - "Prokineticin signaling in normal growth and tumorigenesis": International Journal of Molecular Medicine||Research Achievement|
|2007-10-01||The Best Presentation: 12th World Congress on Advances in Oncology and 10th International Symposium on Molecular Medicine, Greece||Research Achievement|
|2007-03-01||Best Poster Award: Aberrant KLF4 expression and BMP signaling cause proliferation defect in PTC1-/- neural crest cells.: MGH-HKU-Nature China Forum||Research Achievement|
|2010-11-01||Beverly McKinnell Award: The 16th International Conference of the International Society of Differentiation||Research Achievement|
|2017-07-01||Peter Paul Rickham Prize (The Best Paper for Basic Science) - Birth of the first "human BA organoids" hinting on the aetiology and disease progression of isolated biliary atresia: 64th Annual British Association of Paediatric Surgeons Congress, London, U.K., 18-22 July 2017||Research Achievement|
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