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Prof David Lee
BSc (Hons), MA, PhD

 

Research Overview

Mechanobiology, Tissue engineering, Cell engineering, Regenerative medicine, Mesenchymal stem cell, Circadian biology, Cartilage, Organ-on-a-chip

Interests

My main research interests lie in mechanobiology, a research field that lies at the interface between cell biology and bioengineering, involving studying the mechanisms by which cells and tissues resond to the application of mechanical loading. The response of our tissues to mechanical stimuli is critical to maintain healthy physiology and has been implicated in a range of pathologies, ranging from cancer to osteoarthritis. I have published over 100 refereed papers in chondrocyte and stem cell mechanobiology and my work investigating the effect of dynamic compression on inflammatory mediators was recognised by the prestigious Negma Lerads International Prize for Mechanobiology of Cartilage and Chondrocytes. I have been awarded over £5 million in grant funding as principal investigator in the past 10 years, including from the MRC, BBSRC, ESPRC, Wellcome Trust and an international multi-centre Human Frontier Science Program grant investigating mechanoregulation of nuclear organisation and genome function.

My research has largely focussed on musculoskeletal tissues, particularly cartilage and tendon. I have looked at the process by which mechanical forces become transduced into biochemical pathways, for example those linked to MAP kinases and calcium fluxes across the cell membrane. Recent work has looked at stem cells and whether they can be induced to differentiate through mechanical stimuli. My work on mesenchymal stem cells has shown that the application of mechanical force can induce more rapid and robust differentiation than traditional biochemical differentiation cues such as growth factors. Loading seems to have a particularly profound effect on the cell nucleus, inducing alterations in the packing of DNA within chromatin and stiffening the nuclear membrane through changes in the nucleoskeleton.

Recently research has investigated the interplay between mechanobiology and the circadian clock which generates 24-hour cycles of biological activity. These studies are aimed at developing more physiologically relevant in vitro models, for example organ-on-a-chip systems, that may be used in drug discovery and other applications.