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A dynamical model of TGF-β activation in asthmatic airways (2023)
Journal Article
Pybus, H. J., O’dea, R. D., & Brook, B. S. (2023). A dynamical model of TGF-β activation in asthmatic airways. Mathematical Medicine and Biology, 40(3), 238-265. https://doi.org/10.1093/imammb/dqad004

Excessive activation of the regulatory cytokine transforming growth factor β (TGF-β) via contraction of airway smooth muscle (ASM) is associated with the development of asthma. In this study, we develop an ordinary differential equation model that de... Read More about A dynamical model of TGF-β activation in asthmatic airways.

Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis (2023)
Journal Article
Tatler, A. L., Philp, C. J., Hill, M. R., Cox, S., Bullock, A. M., John, A., …Brook, B. S. (2023). Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis. American Journal of Physiology-Lung Cellular and Molecular Physiology, 324(3), L271-L284. https://doi.org/10.1152/ajplung.00034.2022

Airway remodelling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extra-cellular matrix (ECM) deposition. Whilst extensively studied in murine airways, studies report only selected larger airways at one time point m... Read More about Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis.

The role of mathematical models in designing mechanopharmacological therapies for asthma (2022)
Journal Article
Irons, L., & Brook, B. S. (2022). The role of mathematical models in designing mechanopharmacological therapies for asthma. Frontiers in Systems Biology, 2, Article 929426. https://doi.org/10.3389/fsysb.2022.929426

Healthy lung function depends on a complex system of interactions which regulate the mechanical and biochemical environment of individual cells to the whole organ. Perturbations from these regulated processes give rise to significant lung dysfunction... Read More about The role of mathematical models in designing mechanopharmacological therapies for asthma.

Reduced biomechanical models for precision-cut lung-slice stretching experiments (2021)
Journal Article
Pybus, H. J., Tatler, A. L., Edgar, L. T., O’Dea, R. D., & Brook, B. S. (2021). Reduced biomechanical models for precision-cut lung-slice stretching experiments. Journal of Mathematical Biology, 82(5), Article 35. https://doi.org/10.1007/s00285-021-01578-2

Precision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of proremodel... Read More about Reduced biomechanical models for precision-cut lung-slice stretching experiments.

Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading (2020)
Journal Article
Irons, L., Huang, H., Owen, M. R., O'Dea, R. D., Meininger, G. A., & Brook, B. S. (2020). Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading. Journal of Theoretical Biology, 502, Article 110387. https://doi.org/10.1016/j.jtbi.2020.110387

Integrins regulate mechanotransduction between smooth muscle cells (SMCs) and the extracellular matrix (ECM). SMCs resident in the walls of airways or blood vessels are continuously exposed to dynamic mechanical forces due to breathing or pulsatile b... Read More about Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading.

A multiphase multiscale model for nutrient limited tissue growth, Part II: A simplified description (2019)
Journal Article
Holden, E., Chapman, S., Brook, B., & O'Dea, R. (2019). A multiphase multiscale model for nutrient limited tissue growth, Part II: A simplified description. ANZIAM Journal, 61(4), 368-381. https://doi.org/10.1017/S1446181119000130

In this paper, we revisit and extend our recent work (Holden et al. (2018) A multiphase multiscale model for nutrient limited tissue growth, The ANZIAM Journal, 59(4), 499-532), that considers the derivation of an effective macroscale description sui... Read More about A multiphase multiscale model for nutrient limited tissue growth, Part II: A simplified description.

Cellular uptake and efflux of palbociclib in vitro in single cell and spheroid models (2019)
Journal Article
Jove, M., Spencer, J. A., Hubbard, M. E., Holden, E. C., O'Dea, R. D., Brook, B. S., …Twelves, C. J. (2019). Cellular uptake and efflux of palbociclib in vitro in single cell and spheroid models. Journal of Pharmacology and Experimental Therapeutics, 370(2), 242-251. https://doi.org/10.1124/jpet.119.256693

Adequate drug distribution through tumors is essential for treatment to be effective. Palbociclib is a cyclin-dependent kinase 4/6 inhibitor approved for use in patients with hormone receptor positive, human epidermal growth factor receptor 2 negativ... Read More about Cellular uptake and efflux of palbociclib in vitro in single cell and spheroid models.

Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices (2019)
Journal Article
Maarsingh, H., Bidan, C. M., Brook, B. S., Zuidhof, A. B., Elzinga, C. R., Smit, M., …Meurs, H. (2019). Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices. AJP - Lung Cellular and Molecular Physiology, 316(3), L537-L546. https://doi.org/10.1152/ajplung.00325.2018

The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear. We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig... Read More about Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices.

Effect of loading history on airway smooth muscle cell-matrix adhesions (2018)
Journal Article
Irons, L., Owen, M. R., O'Dea, R. D., & Brook, B. S. (2018). Effect of loading history on airway smooth muscle cell-matrix adhesions. Biophysical Journal, 114(11), 2679-2690. https://doi.org/10.1016/j.bpj.2018.04.026

Integrin-mediated adhesions between airway smooth muscle (ASM) cells and the extracellular matrix (ECM) regulate how contractile forces generated within the cell are transmitted to its external environment. Environmental cues are known to influence t... Read More about Effect of loading history on airway smooth muscle cell-matrix adhesions.

A multiphase multiscale model for nutrient limited tissue growth (2018)
Journal Article
Holden, E., Collis, J., Brook, B. S., & O'Dea, R. D. (2018). A multiphase multiscale model for nutrient limited tissue growth. ANZIAM Journal, 59(4), https://doi.org/10.1017/S1446181118000044

In this work, an effective macroscale description is derived for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effect... Read More about A multiphase multiscale model for nutrient limited tissue growth.

In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss (2018)
Journal Article
Chernyavsky, I. L., Russell, R. J., Saunders, R. M., Morris, G. E., Berair, R., Singapuri, A., Chachi, L., Mansur, A. H., Howarth, P. H., Dennison, P., Chaudhuri, R., Bicknell, S., Rose, F. R. A., Siddiqui, S., Brook, B. S., & Brightling, C. E. (2018). In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss. European Respiratory Journal, 51(5), Article 1701680. https://doi.org/10.1183/13993003.01680-2017

Bronchial thermoplasty is a treatment for asthma. Whether during thermoplasty the airway wall fraction exposed to temperatures necessary to affect cells is sufficient to explain its histopathological impact is unclear.
Airway smooth muscle and bronc... Read More about In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss.

A multiphase multiscale model for nutrient limited tissue growth (2017)
Journal Article
Holden, E. C., Collis, J., Brook, B. S., & O'Dea, R. D. (2017). A multiphase multiscale model for nutrient limited tissue growth. ANZIAM Journal, 59, 499-532. https://doi.org/10.21914/anziamj.v59i0.12240

We derive an effective macroscale description for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effective macroscale... Read More about A multiphase multiscale model for nutrient limited tissue growth.

A novel computational model predicts key regulators of chemokine gradient formation in lymph nodes and site-specific roles for CCL19 and ACKR4 (2017)
Journal Article
Jafarnejad, M., Zawieja, D. C., Brook, B. S., Nibbs, R. J., & Moore, J. E. (2017). A novel computational model predicts key regulators of chemokine gradient formation in lymph nodes and site-specific roles for CCL19 and ACKR4. Journal of Immunology, 199(7), 2291-2304. https://doi.org/10.4049/jimmunol.1700377

The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the dist... Read More about A novel computational model predicts key regulators of chemokine gradient formation in lymph nodes and site-specific roles for CCL19 and ACKR4.

Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage (2017)
Journal Article
Baker, M., Brook, B. S., & Owen, M. R. (2017). Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage. Journal of Mathematical Biology, 75(4), 985-1024. https://doi.org/10.1007/s00285-017-1104-y

Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of... Read More about Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage.

Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice (2016)
Journal Article
Hiorns, J. E., Bidan, C. M., Jensen, O. E., Gosens, R., Kistemaker, L. E., Fredberg, J. J., …Brook, B. S. (2016). Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice. Frontiers in Physiology, 7(JUL), Article 309. https://doi.org/10.3389/fphys.2016.00309

The precision-cut lung slice (PCLS) is a powerful tool for studying airway reactivity, but biomechanical measurements to date have largely focused on changes in airway caliber. Here we describe an image processing tool that reveals the associated spa... Read More about Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice.

Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall (2016)
Journal Article
Hiorns, J. E., Jensen, O. E., & Brook, B. S. (2016). Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall. Journal of Applied Physiology, 121(1), 233-247. https://doi.org/10.1152/japplphysiol.00715.2015

Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctua... Read More about Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall.

The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model (2014)
Journal Article

Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM) mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynam... Read More about The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model.