Research Projects
Understanding Human Congenital Diseases: From Capturing the Molecular Dynamics Underlying Cell-State Transition to Delineating the Disease Mechanism Using Mouse and Human Pluripotent Stem Cell (PSC)-Based Models

Neural crest (NC) is a transient population of multipotent progenitor cells in vertebrates, contributing to the formation of various organ systems. Aberrant NC development results in a myriad of birth defects and diseases, such as Hirschsprung (HSCR) disease and congenital septal defects which are attributed to the developmental defects of enteric and cardiac NC, respectively. We utilise an integrated approach with various mouse and pluripotent stem cells (hPSCs)-cell and -organoid based models, single-cell transcriptomic and epigenetic analyses, to identify the key regulators controlling cell-state transition and for a better understanding of the molecular control underlying various congenital diseases.  

Followings are the key research areas:

1. Metabolic programmes in NC cell-fate transition and HSCR disease
   Metabolic rewiring represents an important mechanism during development for balancing the intrinsic needs of a cellular state and the constraints imposed by extrinsic conditions.  It is of a particular interest to delineate how the change of metabolic program may alter the complex landscape of regulatory mechanisms underlying cell differentiation and disease.
2. Selective vulnerability of human neurons in our brain and gut
   Recent advances in stem cell research allow the generation of human CNS and ENS neurons from human pluripotent stem cell (hPSC) to recapitulate disease conditions in vitro with organotypic cell phenotype diversity and tissue structure, representing a powerful model to delineate the genetic links underlying the syndromic conditions of various congenital diseases.
3. Cell-cell communications underlying the valvulogenesis
   Cardiac NCs interact the cardiac endothelial cells to coordinately modulate the cardiac valve development. To develop an effect treatment, we aim to address (1) what are the molecular signalling pathway mediating the cross-talk between the two progenitor populations and (2) how the focal adhesion and cell junction molecules are involved.

Professor ESW Ngan, Department of Surgery

Professor Elly Sau-wai Ngan is a professor in the department of Surgery, LKS Faculty of Medicine. Her main research interest is to translate the genetic data obtained from patients into biology to understand the molecular mechanisms underlying pathogenesis of neural crest associated diseases, with a particular focus on neuroblastoma and Hirschsprung disease (HSCR). Her laboratory has established various disease models using human pluripotent stem cell (hPSC)-derived cell- and organoid models and transgenic/knock-out mice to decode the functional impacts of HSCR associated mutations in enteric nervous system development. The recent focus of her group is to develop methods for generation of functional neurons for cell-based therapy.

Biography
HKU Scholars Hub
Laboratory Homepage
ORCID
engan@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.