Programme(s) to which this project applies: |
☒ MPhil/PhD | ☑ MRes[Med] | ☒ URIS |
Objective and Significance:
Background:
Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality with an incidence of 1 in 10000 live births and a carrier frequency of 1 in 40. This autosomal recessive disorder is inherited and caused by deletion or mutation of the SMN1 (survival motor neuron) gene and retention of its homologue SMN2, which predominantly encodes a truncated and unstable SMN2 protein. This results in overall deficiency of the ubiquitously expressed full-length SMN protein that causes selective degeneration of spinal motor neurons (MNs) and denervation of skeletal muscle, eventually leading to muscular atrophy and death. Thus, the copy number of SMN2 gene is inversely correlated with the severity of SMA symptoms ranging from type I (most severe) to IV (less severe). However, it remains unclear why the loss of SMN, a ubiquitously expressed protein, results in the selective MN death.
Our pilot studies demonstrated that DLC1 isoform 1, which is specially expressed in human embryonic stem cells-derived motor neurons, is crucial for its survival, and DLC1 isoform 1 expression levels are determined by the amount of SMN proteins. In this project, we aim to further consolidate our findings using SMA patient-derived motor neurons that DLC1 isoform 1 expression levels correlate with the amount of SMN protein.
Objectives:
Significance:
Successful implementation of this study will advance our understanding in SMA pathogenesis and therapy:
Knowledge gained in this study will be exploited in future clinical trial design for patients with SMA.
Research Plan and Methodology:
Dr MCH Cheung, School of Biomedical Sciences
I obtained my bachelor's degree in the Department of Biochemistry at the Chinese University of Hong Kong with a first-class honour and then PhD in the University of Nottingham in UK Following postdoctoral training in the National Institute for Medical Research in UK, I returned to Hong Kong in 2007 to join the former Department of Biochemistry in HKU as a Research Assistant Professor and became Assistant Professor in the Department of Anatomy in Nov 2013. I was promoted to Associate Professor with tenure in School of Biomedical Sciences since Nov 2019. My long-term research interest is to dissect the molecular mechanisms underlying the complex cell migration events using neural crest cells in chick embryo as a model system and determine whether similar regulatory control conferring neural crest migratory capacity also governs cancer metastasis.
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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.
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