Microcirculation Research Group

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 (I/R) injury. We have applied I/R injury to various vascular beds, including the gut, mesentery, kidney, liver and cremaster muscle, to understand site specific mechanisms governing microcirculatory perturbations.  We recently developed a novel method to intravitally image the impact of myocardial I/R injury on the coronary microcirculation in a beating heart environment.  We use this model to directly observe thromboinflammatory events within myocardial microvessels, particularly the trafficking, adhesion kinetics (rolling / adhesion / transmigration) and cross-talk between leukocytes and platelets with each other and vascular endothelium.  We are combining this method with laser speckle contrast imaging of the beating heart to quantitate overall organ perfusion and correlate these events with those taking place at the microvascular level. 

Using these powerful tools, we aim to identify novel cellular and molecular mechanisms contributing to coronary microcirculatory dysfunction that can be therapeutically manipulated for clinical benefit.  We are currently focused on the critical proinflammatory role of the IL-36/IL-36R pathway, a novel member of the IL-1 superfamily, in the heart.  Whether contemporary and novel cardiovascular drugs, such as anti-platelets, can be repurposed for treating coronary microcirculatory disturbances post-reperfusion injury is also being investigated.  We are also assessing the vasculoprotective benefits of adult bone marrow-derived stem cells in I/R injured organs, specifically, haematopoietic (HSC) and mesenchymal (MSC) stem cells.  We are developing strategies to enhance stem cell recruitment and their vasculoprotective efficacy using biochemical pre-treatment, 3D culture methods and microfluidic devices.  Determining whether cardiovascular co-morbidities such as ageing and diabetes increase the susceptibility of coronary microcirculation to I/R injury is a central component of the Dr Kalia’s programme of research.

Follow the research activities of the Microcirculation Research Group on Twitter @MRG_UoB

Key Resources

The University recently invested significantly in developing a world-class intravital microscopy facility at the Medical School through the award of a strategic equipment grant.  Dr Kalia is the Director this facility which is the first of its kind in the UK and leads the Imaging and Technology research theme for the Institute.  This facility is fully equipped with multiphoton and spinning disk confocal intravital microscopes, as well as laser Doppler and laser speckle imaging systems.  

The intravital imaging facility will consider collaborations from external parties on any aspects of vascular research - please contact Dr Kalia for further information.

Imaging microvessels in their natural habitat

• Cell-cell interactions
• Real-time thrombosis
• Vascular integrity
• Vascular permeability / leakage
• Functional capillary density
• Blood flow / perfusion
• Blood (cell) / perfusion
• Vessel diameter
• Oxidative stress