Mr Yu Chinn Joshua Chey

PhD Research

A CRISPR cure for Duchenne Muscular Dystrophy

CRISPR/Cas9's therapeutic potential is, without a doubt, incredibly powerful. This cutting-edge gene-editing technology enables fast, precise, and straightforward modification of DNA. It has quickly become the mainstay technique of many research laboratories to manipulate the genome of cells and laboratory animals. There is currently significant research interest in transitioning the use of CRISPR/Cas9 to the clinic and further developing it as therapy for the permanent correction of many different genetic diseases.

Joshua's PhD project involves developing CRISPR/Cas9 editing strategies to permanently correct Duchenne Muscular Dystrophy (DMD). DMD is a severe muscle-wasting disease associated with mutations to the DMD gene located on the X-chromosome. Due to loss-of-function mutations to the DMD gene, patients do not express functional dystrophin protein- an essential membrane stabiliser in striated muscles. Muscle contractions cause damage to the unstable muscle cell membrane, leading to necroptosis and subsequent replacement of muscle with fibrous and fat tissue, manifesting in the progressive loss of muscle strength observed in patients. This disease is ultimately fatal as patients succumb to complications arising from heart and respiratory weakness.

Our CRISPR therapy team is focused on developing CRISPR/Cas9 editing strategies that are safe, effective, and applicable for human DMD patients. Joshua is involved in identifying, testing and tuning strategies that apply to a broad range of DMD mutations, with hopes of identifying the best candidates for further testing in a clinical setting. These strategies intend to permanently change and correct the sequence of patients' DMD gene to restore dystrophin protein expression and halt disease progression.

Joshua is also actively involved in side projects relating to the advancement of CRISPR/Cas9 technology and novel PRIME editing technology.

MPhil Research

Sn'HIF'fing out roles for HIFs in Multiple Myeloma

Joshua's MPhil project is in the areas of hypoxia (state of low oxygen levels) and blood cancer biology. Cellular responses to hypoxia are primarily mediated by the HIFs, which play important roles in both normal physiology and in disease, such as in cancer, infarction and inflammation. While hypoxia is widely recognised as a hallmark of solid tumours, its role in the pathology of liquid tumours is less well understood.

MM is the second most common blood cancer, an incurable haematological malignancy of bone marrow plasma cells that manifests as combination of clinical symptoms known mnemonically as CRAB: hyperCalcaemia, Renal failure, Anaemia, and Bone lesions. As the bone marrow microenvironment is physiologically hypoxic, HIF activation is likely to to contribute to the unfavourable biology of MM through the induction of angiogenesis, metastasis, osteolysis and cell survival.

Using cutting-edge CRIPSR/Cas9 technology, Joshua aims to elucidate HIF's roles in MM pathology to strengthen the rationale for the development of MM therapies that target the hypoxic bone marrow niche and for the repurposing of HIF-inhibitors.

Side projects

In addition to his interests in MM hypoxia, Joshua is also interested in the study of HIF pathway components in both normal and disease biology. He is actively involved in side projects pertinent to the study of Factor Inhibiting HIF (FIH) as a novel regulator of metabolism and the study of HIFs in retinal metabolism.