Faculty of Biological Sciences

Dr Andrew Smith

MBChB 2001, Aberdeen; PhD 2008, Glasgow
Lecturer in Cardiovascular Science
School of Biomedical Sciences

Background: Completed medical degree (MBChB, 2001) at the University of Aberdeen then worked clinically for some years. Carried out research PhD in Neuroscience and Biomedical Systems at the University of Glasgow (2008), then worked as a post-doctoral researcher at Liverpool John Moores University (2009-2013) and at King's College London (2013-2015).

Contact:  Garstang 7.52b, +44(0) 113 343 9804, email address for  

Research Interests

Stem and progenitor cells in cardiovascular tissue: myocardial tissue maintenance

Cardiac tissue maintenance and repair

My interest is in the role played by endogenous cardiac stem cells (eCSCs) within the myocardium and their contribution to tissue in both normal myocardial function and in disease. It has been shown that these cells exhibit defining characteristics of stem cells and can develop into the main cell lineages found within the myocardium: cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts (Smith et al., 2014, Nature Protocols 9(7): 1662-1681) and can repair lost myocardial tissue following injury. 

In my previous work in the laboratory of Dr. Georgina Ellison at King's College London, we investigated the role of these cells in the post-injury setting, in particular their response to diffuse cardiac injury, showing that they play a critical role in myocardial tissue maintenance in this setting (Ellison et al., 2013, Cell 154(4): 827-42). In addition to this, we demonstrated that the application of growth factors via the cornoary blood supply can increase eCSCs' activity, in association with an improved tissue and functional recovery following myocardial infarction (Ellison et al., 2011, Journal of the American College of Cardiology 58: 977-86). 

An additional important aspect of eCSC biology is that these cells can be activated by physiological stimulus, specifically high-intensity exercise (Waring et al., 2012, European Heart Journal 35(39): 2722-2731). The mechanisms underlying this are of interest in my group, with funding applications in place to pursue this further, considering the roles of both cardiac and endothelial stem/progenitor cell populations. 

Cardiac Stem Cells' role in cardiotoxicity

My particular focus at present is on the anti-cancer drugs and known cardiotoxins tyrosine kinase inhibitors (Trk-Is), specifically their effects on eCSCs. I am interested in the Trk-Is’ effects regarding both their impact on the viability and numbers of the eCSC population as a whole and their effects on eCSCs’ characteristics and their role in myocardial tissue maintenance. From this I intend to determine whether Trk-I toxicity is due to their effects on eCSCs and to use this information to identify the role played by different Trk receptors in eCSC biology, in terms of how different second messenger systems associated with Trk receptors affect eCSCs’ characteristics and regenerative potential. This may allow the identification of new avenues for treatment in the specific case of Trk-I-induced cardiotoxicity or potentially a means to manipulate eCSC biology with a view to using these cells’ regenerative potential to treat heart failure more broadly. 

In addition to this main focus of research, I am carrying out collaborative work with colleagues at the University to examine the function of other similar populations of cells in other tissues, with a view to determining the role played by these cells in their respective tissues. 

Collaborations

Dr. Georgina M. Ellison, King's College London

 

Current Projects

Cell death mechanisms in endogenous cardiac stem cells from tyrosine kinase inhibitors.

This study is currently on-going, using human eCSCs that have been isolated from tissue and grown in culture, to examine the mechanisms involved in the toxicity induced by tyrosine kinase inhibitors. Study will focus on the cell death pathways involved and will also examine associated alterations in intracellular calcium and levels of reactive oxygen species (ROS). This project involves isolation of human cells from tissue samples, cell culture, live staining and imaging in multi-well plates and confocal analysis, immunological labelling and molecular biology techniques; with considerable confocal microscope work to examine calcium and ROS labelling. This project is being supervised by Dr. Smith in collaboration with Prof. Derek Steele, and is funded by the School of Biomedical Sciences and the Leeds Anniversary Research Scholarship. 

Novel chemical methods to sample cell surface proteins.

This study is currently on-going, using human cardiovascular cells, which have been isolated from clinical myocardial or vascular tissue samples and placed in culture. We are applying a novel chemical tool to effectively 'biopsy' the cell surface and obtain identifiable proteins, with the intention of being able to characterise the cells without affecting cell survival by this process. This project is currently on-going, in collaboration with Prof. John Colyer (Faculty of Biological Sciences) and Dr. Karen Porter (Faculty of Medicine and Health). 

 

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Current undergraduate projects under my supervision are examining: the alterations in ion channel expression in response to stem cell differentiation in culture; the comparative roles played by endogenous stem cells and pre-existing cardiomyocytes to new cardiomyocyte formation in the adult heart.
  • Further projects will examine the impact of receptor tyrosine kinase inhibitors (RTKIs) on different cell populations within cardiac tissue. The RTKIs are anti-cancer drugs with known cardiotoxic effects, these studies will examine their actions on cardiac fibroblasts and stem/progenitor cells.

See also:

Modules taught

BMSC1103 - Basic Laboratory and Scientific Skills
BMSC1110 - Foundations of Biomedical Sciences
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC2235 - Molecular Neuroscience
BMSC3301 - Research Project in Biomedical Sciences
BMSC3399 - Extended Research Project Preparation

Centre membership: The Multidisciplinary Cardiovascular Research Centre (MCRC)

Dr Kathleen Wright  (Senior Scientific Officer in Cardiovascular Science)

Supporting laboratory research development, training and management in the department of Cardiovascular Sciences 

Postgraduates

Robert Walmsley (Primary supervisor) 50% FTE
Hanan El-Kuwaila (Co-supervisor) 20% FTE
Thomas Sheard (Co-supervisor) 33% FTE