Research Projects
Deep Phenotyping of Immune Cell Populations and Transcriptional Profiling in Paediatric Immunodysregulatory Disorders


Programme(s) to which this project applies:

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

Autoimmune and autoinflammatory diseases cause considerable long-term morbidity and mortality, especially in children. There is a need for patient stratification and outcome prediction to tailor immunosuppressive therapy according to deep knowledge of the pathomechanisms underlying immune dysregulation.

 

Objectives

To identify immune cell phenotype and transcriptomic signatures that characterise childhood-onset autoimmune and immunodysregulatory disorders, using deep phenotyping methods such as flow cytometry and transcriptomic analysis

 

Hypothesis to be tested

We hypothesise that paediatric autoimmune and autoinflammatory diseases have distinct immune cell phenotype and gene expression pattern that can predict disease severity and response to specific disease-modifying treatment.

 

Study instruments

Standardised disease activity measurement, immunophenotyping by flow cytometry, transcriptome profiling by RNA-sequencing

 

Interventions

Patients will be evaluated at diagnosis / disease relapse and after drug treatment for detailed phenotyping of clinical manifestations, immune cells and transcriptome

 

Main outcome measures

Cellular subsets and transcriptome signatures that are predictive of disease remission or persistence

 

Data analysis

Proportion of immune cell subpopulations in each disease entity will be compared in patients before and after treatment at specified time-points, using age-matched healthy controls as reference. Differentially expressed genes identified from transcriptome profiling of T-cells, B-cells and neutrophils will be analysed for pathway enrichment and mapping through bioinformatics pipeline. Genes and pathways that characterise each disease, and those modulated by treatment, will be identified.

 

Expected results

Distinct cellular subpopulations and corresponding gene expression can identify pathways that can be targeted by biologic response modifiers, enabling treatment of autoimmune and autoinflammatory disease using a personalised medicine approach.

About the Supervisor

Dr PPW Lee, Department of Paediatrics and Adolescent Medicine

Clinical Expertise

  • Primary immunodeficiency disorders
  • Paediatric rheumatology

Field of Research

  • Inflammasome biology and immunoregulatory mechanisms of type I interferon signalling
  • Primary immunodeficiencies and immunodysregulatory disorders – Gene discoveries and mechanisms of disease
  • Mesenchymal stromal cell biology in the context of immune dysregulation and cancers

Biography
ppwlee@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.