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.