Personal profile

Overview

Being a previous Cardiologist, my research interest is in the molecular basis of cardiovascular diseases, focusing on genetic small vessel diseases (SVD) and the functions of the causative genes such as NOTCH3, COL4A1/A2, TREX1, in cardiovascular system. We utilise patient-specific induced pluripotent stem cells (iPSCs) as model system to study a range of genetic SVD in order to understand molecular mechanisms of the conditions, and identify biomarkers and therapeutic targets that could be generalised to the more common and sporadic form of SVD. We are particularly interested in understanding how cerebral vascular pathologies lead to the neurodegeneration and vascular dementia by interrogating interactions between different iPSC-derived vascular and neuronal cell types that form the neurovascular unit (NVU) in the brain. My group is also interested in stem cell related vascular tissue engineering and nano-medicine/nano-targeting. 

Biography

2018 - Now       Professor of Molecular Medicine

2014 – 2018      Senior Lecturer, The University of Manchester

2003 – 2013      Lecturer/Research Fellow, The University of Manchester

2001 – 2003      Postdoc, Department of Medical Genetics, University of Cambridge

1992 - 2001       Postdoc, Department of Medicine, University of Cambridge

1986 – 1992      Physician Cardiologist, the 3rd Hospital of Peking University

1988 – 2001      PhD, the 3rd Hospital of Peking University Health Science Centre

1981 – 1986      Medical student, China Medical University    

   

Research interests

Research Interests:

  • Molecular mechanisms of genetic cardiovascular diseases
  • iPSC modelling of genetic vascular and neurovascular conditions
  • Neurovascular interactions and vascular dementia
  • Notch signalling in human cardiovascular system
  • Vascular engineering and Nano-medicine 

iPSC model of genetic cardiovascular and cerebral vascular conditions

Small vessel diseases are among the key risk factors contributing to cognitive defects of the brain, leading to vascular dementia that has been recognised as the second leading form of dementia after Alzheimer’s disease. However, the underlying molecular mechanisms for such conditions are largely under investigated. The most common type of genetic stroke syndrome CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), caused by NOTCH3 gene mutation, is a typical small vassal disease and provides a valuable model to explore the pathogenesis of vascular dementia. CADASIL is a systemic vascular condition, but has a brain-specific clinical manifestation, suggesting a defect in neurovascular coupling. The communications between vascular cells and neuronal cells happen within the neurovascular unit (NVU) in the brain through either physical contacts or releasing trophic factors. We use the patient-specific iPSC model in conjuction with genome editing (CRISPR/Cas9) to explore functional interactions between neurovascular cells, identify therapeutic targets and conduct drug screen for future treatment of vascular dementia.  

Notch signalling in cardiovascular function and diseases

Notch signalling is an evolutionarily conserved pathway that transduces signals between adjacent cells. Notch signalling determines cell fate during embryonic development and are also important in the maintenance of cellular homeostasis in the adult life. Dysregulation of Notch signalling leads to a diverse range of human diseases from cancer to cardiovascular disorders. We are using molecular biology and cell biology tools including high throughput screening to study the role of Notch signalling in cardiovascular and cerebral vascular cells including their differentiation from stem cells, and explore small molecules that could manipulate the signalling in order to achieve targeted treatment for related diseases.

Vascular engineering

In conjunction with the iPSC research and utilising state-of-art material technologies, we are producing functionalised vascular scaffold that could accommodate patient-specific iPSC-derived vascular cells, in order to create personalised vascular grafts to be used for future regenerative therapy, or as a tissue model for the study of molecular mechanisms of genetic vascular diseases and drug targets.

Nanomedicine

Nanotechnologies are transforming the capabilities of medical diagnosis and treatments. We are currently producing and functionalising biodegradable nanoparticles to explore their potential for targeted therapy. We also study the molecular mechanisms of the antimicrobial functions of the laser produced novel metal nanoparticles.   

 

Source of funding:

  • British Heart Foundation (BHF)
  • Medical Research Council (MRC)
  • The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
  • Animal Free Research UK
  • Manchester Institute for Collaborative Research on Ageing
  • Stroke Association
  • Alzheimer’s Research UK
  • Alzheimer’s Society Manchester and Northwest Network Centre
  • The University of Manchester Intellectual Property Limited (UMIP)
  • Johnson & Johnson
  • Central Manchester and Manchester Children's University Hospitals NHS Trust
  • BBSRC

 

Teaching

  • Programme Director: Clinical Genetics and Genetic Counselling (International)

  • Course Director: Fundamentals of Human Genetics. For MSc and STP programmes in Genomic Medicine and Genetic Counselling.

  • Teaching: Human Genetics and Evolution (BIOL 31402). For the 3rd year undergraduate students in Faculty of Life Sciences.

My collaborations

 Current laboratory members:

  • Dr Adam Mitchel
    Postdoctoral Research Associate. iPSCs COL4A1/A2 SVD 
  • Luis Larrea
    CDT PhD Student. Vascular tissue engineering 
  • Katie Newman
    MRC DTP PhD Student. iPSCs RVCL study
  • Xiangjun Zhao
    PhD Student. iPSCs VSMC study 
  • Chaowen Yu
    Visiting Research Fellow. iPSC/CRISPR/lung organoid
  • Srishti Silvano
    MRes Student in Tissue Engineering and Regenerative Medicine  

 

 

Collaborators:

 

  • Professor Sue Kimber
    FBMH, The University of Manchester
  • Professor Nigel Hooper 
    FBMH, The University of Manchester
  • Professor Karen Horsburgh 
    University of Edinburgh
  • Professor Rhian M. Touyz 
    University of Glasgow 
  • Dr Tim Felton
    FBMH, The University of Manchester
  • Prof Anna Blocki
    The Chinese University of Hong Kong
  • Dr Martin Baron
    FBMS, The University of Manchester
  • Professor Pankaj Sharma
    Royal Holloway, University of London and Imperial College London
  • Professor Henry Yi Li
    School of Materials, University of Manchester
  • Dr Jiashen Li
    School of Materials, University of Manchester
  • Professor Lin Li
    School of Mechanical Aerospace and Civil Engineering, University of Manchester
  • Dr Zhu Liu
    School of Materials, University of Manchester
  • Dr Marco Domingos 
    School of Mechanical Aerospace and Civil Engineering, University of Manchester
  • Professor Qingbo Xu
    King’s College London

 

 

Alumni:

 

  • Dr Adam Dickinson 
    Postdoctoral Research Associate
  • Joseph Kelleher 
    NC3Rs PhD Student
  • Wenjun Zhang
    CSC-UoM PhD Student
  • Sumia Ali
    Postdoctoral Research Associate
  • Dr Nazanin Mirhosseini
    Postdoctoral Research Associate
  • Peri Korshed
    PhD Student
  • Sumia Ali
    Postdoctoral Research Associate
  • Samira Hosseini
    PhD Student
  • Dr Jianzhen Ren 
    Visiting Scholar
  • Graeme Elliott
    PhD student. 
  • Adem Sadli
    PhD student
  • Junhong Gui
    PhD student 
  • Yanwen Wang
    PhD student
  • Rebekah Leong 
    MSc student in Bioinformatics
  • Victor Hu 
    Final Year UG project
  • Amerikos Argyriou
    MRes Student in Tissue engineering and regenerative medicine 
  • Jenny Quang
    MRes student in Tissue engineering and regenerative medicine
  • Megan Kelly
    MSci Genetics 
  • Mohammad Hussain 
    MRes student in Tissue engineering and regenerative medicine
  • Ramla Omar
    MRes in Medical Genetics
  • Hector Garcia Romeu
    MRes student in Tissue engineering and regenerative medicine
  • Paul Humphreys
    MRes student in Tissue engineering and regenerative medicine
  • Charles Wade
    MRes in Translational Medicine
  • Madalaine Kay
    MRes student in Tissue engineering and regenerative medicine
  • Lauren Faulkner
    MSc in Medical Genetics
  • Georgi Delchev
    MSc Bioinformatics
  • Qi Li
    MSc Bioinformatics 
  • Arjun Subramanian
    MRes student in Tissue engineering and regenerative medicine
  • Stephanie Frost
    MRes in Medical Genetics
  • George Braileanu 
    MRes in Translational Medicine
  • Zoe Sawitzki
    MRes in Medical Genetics
  • Shiraz Ziya
    MRes in Translational Medicine
  • Kumarini Akurugoda
    MRes in Translational Medicine 
  • Leyla Zilic
    MRes in Translational Medicine
  • Sundas Chohan 
    MRes student in Tissue engineering and regenerative medicine
  • Sabrina Caiazzo
    ERASMURS MSc student, Italy 
  • Andrew Robinson
    MRes in Translational Medicine
  • Chris Breen
    MRes in Translational medicine
  • Nadim Lukas
    Final year UG project student
  • Zhi Zheng
    Final year UG project student
  • Xuting Ye
    Finak year UG project student
  • Chiheng Xu
    Final year UG project
  • Anqi Zhang
    MSc Cell Biology regenerative medicine
  • Chiheng Xu
    Final year UG project 

 

 

 

Memberships of committees and professional bodies

  • Member of British Society for Cardiovascular Research
  • Member of British Atherosclerosis Society
  • Member of the International Society for Stem Cell Research
  • Guest Editor: Cardiovascular Disease and Vascular Tissue Engineering (Cells, special issue)
  • Managing Editor: Signalling Pathways in Cardiovascular Function and Diseases (FBS special issue)
  • Member of Editorial Board: American Journal of Clinical and Experimental Medicine
  • Member of Editorial Board: Annals of Stroke and Vascular Neurology
  • Editorial Board member: Bioscience Research Institute (BRI)
  • Editorial Board member: Frontiers in Bioscience Scholar
  • Editorial Board member: Frontiers in Bioscience-Elite
  • Topic Editor: Pharmaceutics 
  • Member of Editorial Board, Signal Transduction Insights (an online journal)
  • Member of Editorial Board (previous), Recent Patents on CNS Drug Discovery
  • Overseas Editor for Chinese Journal of Biochemistry and Molecular Biology (CJBMB)
  • Overseas Editor for Chinese Journal of Cardiovascular Review

Methodological knowledge

  • Molecular biology
  • Cell biology including iPSCs
  • Protein chemistry
  • Functional enzymology
  • In vitro pharmacology
  • Molecular genetics

Qualifications

1986 MBChB, China Medical University

1991 PhD, Peking University Health Science Centre

2017 SFHEA (Senior Fellow of Higher Education Academy, UK)

2021 FRSB (Fellow of Royal Society of Biology) 

2022 FRSM (Fellow of Royal Society of Medicine)

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 14 - Life Below Water

External positions

Guest Professor, Peking University

Jan 2018 → …

Research Beacons, Institutes and Platforms

  • Dementia@Manchester
  • Manchester Regenerative Medicine Network
  • Christabel Pankhurst Institute
  • Manchester Institute for Collaborative Research on Ageing

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