About
Dr Liku Bekele Tezera is a Senior Research Fellow and Anniversary Fellow within the Faculty of Medicine at the University of Southampton.
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Research
Research interests
- Physiologically relevant in vitro models for chronic bacterial infections that capture host mechanics and microenvironments.TB granuloma mechanobiology.Mechanotransduction pathways, including YAP/TAZ, SRF/MRTF, integrins and TRP channels.Host-directed therapy screening across defined stiffness states.Validating 3D models against patient samples to reduce animal use
Current research
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Liku’s research interest is the development of a physiologically relevant in vitro environment model that mimics the in vivo environment in chronic bacterial infections, including the mechanical pressure experienced by the host and the bacteria. As a model, he has worked on granuloma formation in Tuberculosis (TB), which is recognised as evidence of established infection. Development of a 3D-model system for M.tuberculosis (Mtb) is critical in the TB field as research relies heavily on animal models, which do not entirely reflect the pathology that occurs in human TB. One of the central models he is working on utilises cellular bioelectrospray technology to encapsulate human cells, extracellular matrix components and live Mtb. Using specially designed encapsulation techniques, many microspheres can be rapidly generated and utilised for studying host-pathogen interactions (Advanced Functional Materials 2014; 24: 2648-2657). Results demonstrate that cells have excellent viability, aggregate in a collagen-alginate matrix, and secrete cytokines and proteases when stimulated with Mtb (eLife, 6(e21283), 1-19). There is also comparable growth of Mtb in the microsphere matrix as in liquid media, making this in vitro model a viable alternative to reduce the requirement for TB animal modelling for antimycobacterial drug activity (mBio,2017 8(1), 1-14) and host-directed therapy (Clinical Infectious Diseases, 2017.10(1093)). In collaboration with colleagues, they have demonstrated that using this engineering/biological strategy, events in 3D reflect events in patients more accurately than in 2D (JCI. 2021 131: 15.), and they have dissected the differential effect of cytokines (JCI. 2021;131(10): e142014.). This 3D-model system for Mtb not only provides novel insights into tuberculosis disease pathogenesis but also provides a platform which can be used to replace animal experimentation in both infectious and non-infectious inflammatory diseases. The model will serve as a springboard into other fields for non-infectious diseases characterised by inflammatory cell infiltrate and matrix destruction, such as other granulomatous diseases of the lung, rheumatoid arthritis, atherosclerosis and cancer cell invasion. In his latest endeavour, he is examining the role of matrix stiffness in host-pathogen signalling, using funding from the Academy of Medical Sciences Springboard award. Early findings reveal exciting results. |
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Supervision
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Teaching
- Communicable Disease Control in Master of Public Health (Co-Module Leader)
- Immunity and Infection module for iPhD-DTP (Deputy Module Leader)
- Graduate Group Facilitator BM4 programme
- MMedSc project Supervision and Assessment
- Personal Academic Tutor
- NATS3006-Drugs of the Future: Designing a Magic Bullet (Lecturer)
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Biography
He did his medical and postgraduate training in medical microbiology at Addis Ababa University, Ethiopia and his PhD in from the University of the West of England, Bristol, UK in Cellular Microbiology through an international student’s research scholarship award. His thesis was about the role of PPAR-γ in innate immunity to pathogenic and commensal Neisseria in the nasopharyngeal mucosa. He joined Jon Friedland’s and Paul Elkington’s group at Imperial College as a postdoctoral research fellow in 2011, where he began developing in vitro granuloma models of tuberculosis to investigate the pathology of M. tuberculosis (Mtb) infection. He moved to the University of Southampton in 2012 with Paul Elkington’s research group, where he established a novel 3-dimensional model system for Mtb using a bioelectrospraying technique. This technique involves an engineering approach to incorporate extracellular matrix (ECM), mycobacteria, and different human cells to form an in vitro granuloma system. Using this engineered in vitro granuloma model, he studies the host-pathogen interaction, particularly the role of various ECM components in regulating the well-being of host cells and the growth of Mtb in the granuloma. He has received funding from the National Centre for Replacement, Refinement and Reduction (NC3Rs) of animals in research, the National Institutes of Health (NIH), USA, Medical Research Council, UK and local charities, including Wessex Medical Research and Asthma, Allergy and Inflammation Charity. His latest award is from the Academy of Medical Sciences to investigate mechanotransduction in Tuberculosis in search of therapeutic targets, and he has a plan to extend this approach to chronic bacterial infections.
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