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


Programme(s) to which this project applies:

☑ MPhil/PhD ☒ MRes[Med] ☑ URIS
About the Project

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.
About the Supervisor

Professor ESW Ngan, Department of Surgery

Prof Ngan has completed her PhD from the University of Hong Kong and received her postdoctoral training in Baylor College of Medicine, Houston, USA. Currently, she is the Professor of the University of Hong Kong. She has published her research findings in various prestigious journals including Gastroenterology, Science Advances, Genome Biology, Journal of Clinical Investigation, Journal of National Cancer Institute and PNAS.  She has been serving as the member of the scientific and organization committees of various international conferences and the editorial board member of various reputed scientific journals.

Biography
Laboratory Homepage
engan@hku.hk

Next Step?

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.