Microcirculation Research Group

Neena banner for microcirculation group v1

Group leader: Dr Neena Kalia

Overview

Dysfunctional microcirculation is a hallmark of many diseases.  Our research focuses on using specialist intravital microscopy (IVM) to assess the central role the microcirculation plays in experimental models of injury.  We are able to directly image and quantitate a range of microvascular perturbations which include thromboinflammatory derangements as well as changes in tissue perfusion, functional capillary density and microvascular tone. 

Our research group

We specialise in real-time intravital imaging of microcirculatory disturbances that accompany ischaemia-reperfusion injury (IRI). We have applied IRI to various vascular beds (e.g. gut, mesentery, kidney, liver, cremaster muscle) to understand the mechanisms governing site specific microcirculatory perturbations.  We have also recently developed a novel method to intravitally image the impact of myocardial IRI on the coronary microcirculation in a beating heart environment.  We can directly observe thromboinflammatory events within myocardial microvessels, particularly the trafficking, adhesion kinetics (rolling / adhesion / transmigration) and cross-talk between fluorescently labelled neutrophils, platelets, lymphocytes and monocytes.  We are combining this method with laser speckle contrast imaging of the beating heart (LSCI) to quantitate overall organ perfusion and correlate with events taking place at the microvascular level. 

Using these powerful tools, we aim to identify novel mechanisms of IRI-induced coronary microcirculatory dysfunction that can be therapeutically  manipulated for clinical benefit.  We are currently focused on the critical pro-inflammatory role for the IL-36/IL-36R pathway, a novel member of the IL-1 superfamily, in the heart.  We are also assessing the vasculoprotective benefits of adult bone marrow-derived stem cells in IR injured organs, specifically, haematopoietic (HSC) and mesenchymal stem cells (MSC).  We are developing strategies to enhance stem cell recruitment and their vasculoprotective efficacy and have ongoing studies investigating the benefits of biochemical pre-treatment, 3D culture methods and separation using microfluidic devices.  Since cardiovascular disease commonly occurs in the presence of co-morbidities, we are also investigating the impact of ageing and diabetes on the coronary microcirculation and how these risk factors increase the susceptibility of the heart to IRI.

Key Resources

The main technique we utilise is state-of-the-art fluorescent IVM  which can directly image tissue/organ microcirculation in real-time at a cellular level.  We are one of the most fully equipped IVM facilities, housing a number of different sophisticated microscopes.  These include spinning Nipkow disk confocal-based IVM, multiphoton-based IVM and laser speckle contrast imaging (LSCI). 

Key Resources for microcirculation group

 

 

Current Projects

  • Enhancing the vasculoprotective effects of stem cells (HSCs and MSCs) in IR injured organs
  • Identification of vasculoprotective stem cell sub-types
  • Role of the IL-36/IL-36R pathway in myocardial ischemia-reperfusion injury
  • Role of the IL-36/IL-36R pathway in liver disease
  • Impact of ageing on the coronary microcirculation
  • Impact of diabetes on the coronary microcirculation
  • Identifying anti-platelets drugs that are effective in IR injured coronary microcirculation

Recent Publications

For full publication lists see:

Staff

Principal Investigator
Dr Neena Kalia                 

Postdoctoral Researchers
Dean Kavanagh

PhD Students
Adam Boulton
Joseph Robinson
Rebecca White
Adrian Yemm

Internal Collaborators
Prof David Adams
Prof Chris Buckley
Dr Trish Lalor
Prof Gerard Nash
Dr Phil Newsome
Prof Ed Rainger
Prof Steve Watson

NHS Collaborators
Dr Lorraine Harper - University Hospitals Birmingham NHS Trust, UK
Dr Stuart Smith - University Hospitals Birmingham NHS Trust, UK

External Collaborators
Prof Stuart Egginton - University of Leeds
Prof Jim Middleton - University of Bristol
Prof Caroline Savage – Vice-President and Head Experimental Medicine Unit, GlaxoSmithKline