Imperial College London

ProfessorJamesMoore Jr

Faculty of EngineeringDepartment of Bioengineering

The Bagrit & RAEng Chair in Medical Device Design
 
 
 
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Contact

 

+44 (0)20 7594 9795james.moore.jr CV

 
 
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Location

 

414Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

102 results found

Jafarnejad M, Zawieja DC, Brook BS, Nibbs RJB, Moore JEet al., 2017, A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4., J Immunol, Vol: 199, Pages: 2291-2304

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 distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients. Importantly, the model recapitulates CCL21 gradients observed experimentally in B cell follicles and interfollicular regions, building confidence in its ability to accurately predict intranodal chemokine distribution. Parameter variation analysis indicates that the directionality of these gradients is robust, but their magnitude is sensitive to these key parameters: chemokine production, diffusivity, matrix binding site availability, and CCR7 abundance. The model indicates that lymph flow shapes intranodal CCL21 gradients, and that CCL19 is functionally important at the boundary between B cell follicles and the T cell area. It also predicts that ACKR4 in LNs prevents CCL19/CCL21 accumulation in efferent lymph, but does not control intranodal gradients. Instead, it attributes the disrupted interfollicular CCL21 gradients observed in Ackr4-deficient LNs to ACKR4 loss upstream. Our novel approach has therefore generated new testable hypotheses and alternative interpretations of experimental data. Moreover, it acts as a framework to investigate gradients at other locations, including those that cannot be visualized experimentally or involve other chemokines.

JOURNAL ARTICLE

Jafarnejad M, Zawieja DC, Brook BS, Nibbs RJB, Moore JEet al., 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, Vol: 199, Pages: 2291-2304, ISSN: 0022-1767

JOURNAL ARTICLE

Bertram CD, Macaskill C, Moore JE, 2016, Pump function curve shape for a model lymphatic vessel, Medical Engineering & Physics, Vol: 38, Pages: 656-663, ISSN: 1350-4533

JOURNAL ARTICLE

Jamalian S, Davis MJ, Zawieja DC, Moore JEet al., 2016, Network Scale Modeling of Lymph Transport and Its Effective Pumping Parameters, PLOS ONE, Vol: 11, Pages: e0148384-e0148384

JOURNAL ARTICLE

Jafarnejad M, Cromer WE, Kaunas RR, Zhang SL, Zawieja DC, Moore JEet al., 2015, Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 308, Pages: H697-H706, ISSN: 0363-6135

JOURNAL ARTICLE

Jafarnejad M, Woodruff MC, Zawieja DC, Carroll MC, Moore JEet al., 2015, Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes, LYMPHATIC RESEARCH AND BIOLOGY, Vol: 13, Pages: 234-247, ISSN: 1539-6851

JOURNAL ARTICLE

Wilson JT, van Loon R, Wang W, Zawieja DC, Moore JEet al., 2015, Determining the combined effect of the lymphatic valve leaflets and sinus on resistance to forward flow, JOURNAL OF BIOMECHANICS, Vol: 48, Pages: 3584-3590, ISSN: 0021-9290

JOURNAL ARTICLE

Bazigou E, Wilson JT, Moore JE, 2014, Primary and secondary lymphatic valve development: Molecular, functional and mechanical insights, MICROVASCULAR RESEARCH, Vol: 96, Pages: 38-45, ISSN: 0026-2862

JOURNAL ARTICLE

Bertram CD, Macaskill C, Davis MJ, Moore JEet al., 2014, Development of a model of a multi-lymphangion lymphatic vessel incorporating realistic and measured parameter values, BIOMECHANICS AND MODELING IN MECHANOBIOLOGY, Vol: 13, Pages: 401-416, ISSN: 1617-7959

JOURNAL ARTICLE

Bertram CD, Macaskill C, Moore JE, 2014, Incorporating measured valve properties into a numerical model of a lymphatic vessel, COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING, Vol: 17, Pages: 1519-1534, ISSN: 1025-5842

JOURNAL ARTICLE

Hayman D, Bergerson C, Miller S, Moreno M, Moore JEet al., 2014, The Effect of Static and Dynamic Loading on Degradation of PLLA Stent Fibers, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 136, ISSN: 0148-0731

JOURNAL ARTICLE

Jafarnejad M, Cromer WE, Kaunas RR, Zawieja DC, Moore JEet al., 2014, CALCIUM REGULATION IN LYMPHATIC ENDOTHELIAL CELLS UNDER FLOW, 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013), Publisher: AMER SOC MECHANICAL ENGINEERS

CONFERENCE PAPER

Rahbar E, Akl T, Cote GL, Moore JE, Zawieja DCet al., 2014, Lymph Transport in Rat Mesenteric Lymphatics Experiencing Edemagenic Stress, MICROCIRCULATION, Vol: 21, Pages: 359-367, ISSN: 1073-9688

JOURNAL ARTICLE

Zawieja D, Gashev A, Gasheva O, Davis M, Moore J, Muthuchamy Met al., 2014, Phenotypic characterization of lymphatic contractile activity, 11th International Symposium on Resistance Arteries from Molecular Machinery to Clinical Challenges, Publisher: KARGER, Pages: 61-61, ISSN: 1018-1172

CONFERENCE PAPER

Jamalian S, Bertram CD, Moore JE, 2013, Initial steps toward development of a lumped-parameter model of the lymphatic network

CONFERENCE PAPER

Jamalian S, Bertram CD, Richardson WJ, Moore JEet al., 2013, Parameter sensitivity analysis of a lumped-parameter model of a chain of lymphangions in series., Am J Physiol Heart Circ Physiol, Vol: 305, Pages: H1709-H1717

Any disruption of the lymphatic system due to trauma or injury can lead to edema. There is no effective cure for lymphedema, partly because predictive knowledge of lymphatic system reactions to interventions is lacking. A well-developed model of the system could greatly improve our understanding of its function. Lymphangions, defined as the vessel segment between two valves, are the individual pumping units. Based on our previous lumped-parameter model of a chain of lymphangions, this study aimed to identify the parameters that affect the system output the most using a sensitivity analysis. The system was highly sensitive to minimum valve resistance, such that variations in this parameter caused an order-of-magnitude change in time-average flow rate for certain values of imposed pressure difference. Average flow rate doubled when contraction frequency was increased within its physiological range. Optimum lymphangion length was found to be some 13-14.5 diameters. A peak of time-average flow rate occurred when transmural pressure was such that the pressure-diameter loop for active contractions was centered near maximum passive vessel compliance. Increasing the number of lymphangions in the chain improved the pumping in the presence of larger adverse pressure differences. For a given pressure difference, the optimal number of lymphangions increased with the total vessel length. These results indicate that further experiments to estimate valve resistance more accurately are necessary. The existence of an optimal value of transmural pressure may provide additional guidelines for increasing pumping in areas affected by edema.

JOURNAL ARTICLE

Moore J, Maitland DJ, 2013, Biomedical Technology and Devices, Second Edition, Publisher: CRC PressI Llc, ISBN: 9781439859599

This book explores diverse technological functions and procedures including signal processing, auditory systems, magnetic resonance imaging, ultrasonic and emission imaging, image-guided thermal therapy, medical robotics, shape memory ...

BOOK

Richardson WJ, van der Voort DD, Wilson E, Moore JEet al., 2013, Differential Orientation of 10T1/2 Mesenchymal Cells on Non-Uniform Stretch Environments, MOLECULAR & CELLULAR BIOMECHANICS, Vol: 10, Pages: 245-265, ISSN: 1556-5297

JOURNAL ARTICLE

Wilson JT, Wang W, Hellerstedt AH, Zawieja DC, Moore JEet al., 2013, Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 135, ISSN: 0148-0731

JOURNAL ARTICLE

Davis MJ, Moore JE, Zawieja DC, Gahsev AA, Scallan JPet al., 2012, Lymphatic valve lock in response to modest gravitational loads: a contributing mechanism to peripheral lymphedema?, Experimental Biology Meeting, Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638

CONFERENCE PAPER

Jamalian S, Moore JE, Bertram CD, Richardson Wet al., 2012, PARAMETER SENSITIVITY ANALYSIS OF A LUMPED-PARAMETER MODEL OF LYMPHANGIONS IN SERIES, ASME Summer Bioengineering Conference (SBC), Publisher: AMER SOC MECHANICAL ENGINEERS, Pages: 345-346

CONFERENCE PAPER

Rahbar E, Weimer J, Gibbs H, Yeh AT, Bertram CD, Davis MJ, Hill MA, Zawieja DC, Moore JEet al., 2012, Passive Pressure-Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions, LYMPHATIC RESEARCH AND BIOLOGY, Vol: 10, Pages: 152-163, ISSN: 1539-6851

JOURNAL ARTICLE

Richardson WJ, van der Voort DD, Moore JE, 2012, A DEVICE TO SUBJECT CELLS TO LONGITUDINAL STRETCH GRADIENTS ON A TUBE IN VITRO, ASME Summer Bioengineering Conference (SBC), Publisher: AMER SOC MECHANICAL ENGINEERS, Pages: 1231-1232

CONFERENCE PAPER

Wilson JT, Jafarnejad M, Walsh P, Zawieja DC, Kaunas R, Moore JEet al., 2012, DEVELOPING A MODEL FOR MASS TRANSPORT OF NITRIC OXIDE IN THE LYMPHATIC SYSTEM, ASME Summer Bioengineering Conference (SBC), Publisher: AMER SOC MECHANICAL ENGINEERS, Pages: 343-344

CONFERENCE PAPER

Bertram CD, Macaskill C, Moore JE, 2011, Simulation of a Chain of Collapsible Contracting Lymphangions With Progressive Valve Closure, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 133, ISSN: 0148-0731

JOURNAL ARTICLE

Davis MJ, Rahbar E, Gashev AA, Zawieja DC, Moore JEet al., 2011, Determinants of valve gating in collecting lymphatic vessels from rat mesentery, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 301, Pages: H48-H60, ISSN: 0363-6135

JOURNAL ARTICLE

Rahbar E, Moore JE, 2011, A model of a radially expanding and contracting lymphangion, JOURNAL OF BIOMECHANICS, Vol: 44, Pages: 1001-1007, ISSN: 0021-9290

JOURNAL ARTICLE

Rahbar E, Mori D, Moore JE, 2011, Three-dimensional Analysis of Flow Disturbances Caused by Clots in Inferior Vena Cava Filters, JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY, Vol: 22, Pages: 835-842, ISSN: 1051-0443

JOURNAL ARTICLE

Richardson WJ, Metz RP, Moreno MR, Wilson E, Moore JEet al., 2011, A Device to Study the Effects of Stretch Gradients on Cell Behavior, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 133, ISSN: 0148-0731

JOURNAL ARTICLE

Timmins LH, Miller MW, Clubb FJ, Moore JEet al., 2011, Increased artery wall stress post-stenting leads to greater intimal thickening, LABORATORY INVESTIGATION, Vol: 91, Pages: 955-967, ISSN: 0023-6837

JOURNAL ARTICLE

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