The Bond Lab

Bond Lab research

Dr Mark Bond did his PhD at the University of Bristol, under the supervision of Prof. Andrew Newby. His PhD research focussed on the transcriptional regulation of matrix metalloproteinase (MMPs) by mitogens and inflammatory cytokines and highlighted a major role of the NF-kB transcription factor in the upregulation of MMP-1, -3 and -9.

After completing his PhD, Dr Bond joined Prof. Andrew Baker's group and worked on the mechanisms underlying the pro-apoptotic properties of the MMP inhibitor TIMP-3. TIMP-3 is a secreted ECM-binding protein that is able to induce death of vascular smooth muscle cells. These properties are currently being developed by Prof. Baker's group as a novel gene therapy approach to treat late vein graft failure. Dr Bond characterised how the TIMP-3 protein induced apoptotic cell death of smooth muscle cells and established that this is dependent on the protease inhibitory function of TIMP-3. TIMP-3 was found to induce cell death via a FADD-dependent type II pathway.

After completing his post-doctoral research post in Prof Baker's group, he turned his attention to the mechanisms regulating the proliferation of vascular smooth muscle cells. These cells are normally quiescent in healthy blood vessels, but their proliferation rate can be dramatically increased in response to vessel injury or insult, where it promotes neointima formation after angioplasty and contributes toward late vein graft failure. Dr Bond focused on the second messenger, 3′, 5′-cyclic adenosine monophosphate (cAMP). At this time, cAMP had been recognised to have numerous vascular protective properties and had been shown to inhibit VSMC proliferation, although the underlying mechanisms were not known. His research established that the growth inhibitory properties of cAMP signalling in VSMC are mediated via two central cAMP-sensitive proteins, namely Protein Kinase-A (PKA) and Exchange Protein Activated by cAMP (EPAC). The two pathways act together to inhibit the activity of members of the Rho GTPases, which control actin cytoskeleton polymerisation and organisation. Dr Bond's research demonstrated that this disruption of actin polymerisation was a key step in cAMP-mediated growth arrest. He went on to link these changes in the actin cytoskeleton to transcription of genes needed for cell proliferation, showing that two key transcription factors, MKL and TEAD, play a central role in this.

Dr Bond's work on cAMP highlighted the central role of the actin cytoskeleton in integrating multiple upstream signals and regulating appropriate cellular responses. His current research is focussing on how these mechanisms are involved in regulating cell behaviour during a number of pathological processes that underly cardiovascular disease. These include sensing changes in cardiac and arterial tissue stiffness and regulating cardiac fibrosis and VSMC phenotypic modulation. How actin monomers can translocate into the nucleus and control expression of genes that regulate these processes remains an important focus of our research. Investigating the mechanosensitive and cAMP sensitive transcription factors led to identification of a key role for YAP-TEAD and NFY transcription factors in driving cell hyperplasia and fibrosis. Using molecular docking, the group have identified small molecule inhibitors of these transcription factors and shown that they work to selectively block gene expression driven by these factors.

Dr Bond has 30 years of post-doc research experience in the field of cardiovascular molecular cell biology. The research group now focuses on uncovering the molecular mechanisms that drive cardiovascular disease and related conditions. Combining computational modelling, molecular cell biology, and experimental approaches, the team works to identify and characterise novel therapeutic targets, with a particular emphasis on transcriptional regulation and cell signalling pathways.

A key interest of the group lies in its integration of in silico drug discovery with laboratory validation, enabling the rapid development of innovative small molecules with potential clinical applications. Through interdisciplinary collaboration, the Bond Lab aims to translate fundamental scientific insights into tangible advances in treatment, contributing to improved outcomes for patients with cardiovascular and other chronic diseases.

Please visit the publications page for an up to date list of our publications. More background is on the Bond Lab research page.