Being a previous Cardiologist, my research interest is on the study of cerebral small vessel diseases (cSVDs) and vascular dementia (VaD). We employ induced pluripotent stem cell (iPSC) as a human model system, in conjunction with the CRISPR/Cas9 gene editing, organ-on-chip and organoids technologies, to explores how SVDs result in failure of neurovascular interaction, neurodegeneration, and inflammation, aiming to understand disease mechanisms, identifies biomarkers and therapeutic targets, and translates the research into patient benefits. I am particularly interested in genetic cSVDs, and in the meantime explore how common genetic variants increase the susceptibility of cSVD leading to vascular cognitive defect and dementia. In collaboration with industry (AstraZeneca), we also use iPSC model to study neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) for drug development. My other research interests are on stem cell related vascular tissue engineering and nano-medicine/nano-targeting. 

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:

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

iPSC model of genetic cerebral vascular and neurodegenerative conditions

Small vessel diseases (SVD) 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 not fully understood, thus, there are no specific and effective treatments available. The aetiologies of SVD are heterogeneous including hypertension, atherosclerosis, diabetes mellitus and aging, but a group of genetic SVD provides simple and valuable models to explore the pathogenesis for understanding vascular dementia in general. We are currently working on iPSC models of the most common genetic stroke and dementia syndrome CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) caused by NOTCH3 gene variants, and SVDs caused by variants in genes such as COL4A1/A2, TREX1. The brain brain-specific clinical manifestations in SVD suggest a defect in the communications between vascular cells and neuronal cells within the neurovascular unit (NVU) in the brain through direct or indirect mechanisms. My group has extensive expertise in reprogramming iPSC, CRISPR/Cas9 genome editing, and differentiating iPSCs into a range of neurovascular cell types. We use 2D and 3D models to study neurovascular interactions, blood-brain barrier (BBB) function and cerebral flow regulation, aiming to identify therapeutic targets and conduct drug screen for future treatment of vascular dementia. Our iPSC model has now extended to neurodegenerative conditions like ALS as an in vitro human model system for drug development.

Media coverage: https://www.youtube.com/watch?v=BWKCV32-92k  

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 tissue 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 drug delivery and therapy. 

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
• AstraZeneca
• 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

• Programme Director: Clinical Genetics and Genetic Counselling (International) (2016-22)
• Course Director: Fundamentals of Human Genetics and Genomics (BIOL67561). For MSc and STP programmes in Genomic Medicine and Genetic Counselling.
• Teaching: Disease Modelling (BIOL67672). For MSc and STP students
• Academic Tutor and Advisor, Programme of Biomedical Science (BIOL10000)
• PBL Tutor, Medicine MBChB
• Biosciences International Summer School. Topic: IPSC and CRISPR/Cas9 Gene Editing

 Current laboratory members:

• Xiangjun Zhao
  Postdoctoral Research Associate. ALS iPSC model
  (PhD work: iPSC CADASIL)
• Dr Jessical Wiseman
  Postdoctoral Research Associate. ALS iPSC model 
• Justin Engelbert
  Research Techanician. ALS iPSC model
• Katie Newman
  MRC DTP PhD Student. iPSCs RVCL-S
• Xuwei Qi
  PhD Student. COL4A1/A2 SVD 
• Min Fang
  PhD student. Exosomes in NVU interaction
• Dr Rosanne Reitsema
  EFIS-IL Fellow. iPSC VSMCs
• Dr Chengrong Bao
  Academic Visiting Scholar
• William Hart
  MB PhD. Microglia and inflammation in SVD
• Huishuang Chen
  CSC-UoM PhD student. iPSC CADASIL and NOTCH3 variants
• Charllotte Gill
  MSc Student in Genomic Medicine. NOTCH3 and CADASIL 
• Meghna Singh
  MSc Student in Genomic Medicine. NOTCH3 and CADASIL 
• Peiqing Li
  MSc Student in Clinical Chemistry. Notch3 signalling 

Collaborators:

• Professor Sue Kimber
  FBMH, The University of Manchester
• Professor Nigel Hooper 
  FBMH, The University of Manchester
• Professor Karen Horsburgh 
  University of Edinburgh
• Professor Stuart Allan
  FBMS, The University of Manchester
• Professor Rhian M. Touyz 
  University of Glasgow 
• Dr Tim Felton
  FBMH, The University of Manchester
• Prof Anna Blocki
  The Chinese University of Hong Kong
• 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

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 
• Tsz Ching Kong
  MSc in Genomic Medicine
• Ola Al Dulaimi
  MSc in Genomic Medicine
• Mia Hanlon
  MSc in Genomic 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
• Santhiya Rajan
  MSc in Genomic Medicine
• Charllotte Towch
  MSc in Genomic 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 

• 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

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

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)