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Deciphering protective factors for intervertebral disc degeneration for mechanistic insights and intervention potentials

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Intervertebral disc degeneration (IDD) can lead to a diversity of problems including low back pain and sciatica as two very painful symptomatic outcomes. It is a leading burden in community heath for quality of life in an ageing population globally. Currently, there are no biological treatments for IDD, and surgical interventions are salvage procedures when function of the disc has failed, and the defective disc is removed, and the vertebral segments are either fused, or an artificial disc is implanted. While there are many environment factors such as life style and ageing will contribute to an accelerated outcome, studies have shown that genetic has a major effect with a hereditary index up to 70% from familial and twin studies. While a goal in genetic studies is to identify risk factors that will provide vital clues to the cause of the disease, finding protective factors are equally, if not more important, from a therapeutic perspective. There are indeed “super normal” individuals in our population who are protected against the strong effect of aging from IDD. However, to study the genetics of these individuals is limited from small size cohort of the super normal individuals. Here, we will take advantage of a mouse model that we have generated, expressing a known human genetic risk factor, ASPN, in the mouse disc, causing cellular and extracellular matrix changes consistent with degeneration. Importantly, when breed into the genetic background of a super healer mouse strain, LG/J, the degenerative process is minimized or prevented, and the underlying reason must be related to the genetic variants in key genes/pathways the LG/J mice conferring such a protection. Together, these mouse models provide an ideal opportunity to map/decipher the genes providing the protective effect, and aim to perform a linkage study using these mice to decipher the protective factors for a human risk factor for IDD, ASPN. We will use state-of-the-art next generation sequencing for genetic mapping, combining with single cell RNA sequencing to understand the impact on cellular outcomes; thus providing mechanistic insights, correlating protective genetic variations to IDD outcomes for discovering potential new therapeutic strategies.

You can find more information here: https://www.sbms.hku.hk/staff/danny-chan

Supervisor

Graduated from the University of Melbourne, with a Bachelor of Science (degree with honours), Master of Science and PhD, Prof Chan continued research at his alma mater on heritable skeletal disorders with a focus on extracellular matrix proteins. He joined the University of Hong Kong in 1998, maintaining his research in skeletal biology using mouse as a model to address disease mechanisms in vivo, as well as human genetic studies to define genetic risk factors for common degenerative skeletal conditions such as intervertebral disc degeneration. His research contributed to the molecular understanding of many forms of the human osteochondrodysplasias. In recognition, he was presented with “The Premier’s Award for Health & Medical Research in Victoria, Australia; and more recently, he received the Croucher Senior Fellowship from the Croucher Foundation as recognition of his contribution to skeletal research in Hong Kong.

You can find more information here: http://hub.hku.hk/cris/rp/rp00540

You can also see more details about the Faculty here: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

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