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Your search keyword '"Griffith, Linda G."' showing total 23 results
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23 results on '"Griffith, Linda G."'

1. An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii

Author

Zhang, Jianbo, Huang, Yu-Ja, Trapecar, Martin, Wright, Charles, Schneider, Kirsten, Kemmitt, John, Hernandez-Gordillo, Victor, Yoon, Jun Young, Poyet, Mathilde, Alm, Eric J., Breault, David T., Trumper, David L., Griffith, Linda G., Zhang, Jianbo, Huang, Yu-Ja, Trapecar, Martin, Wright, Charles, Schneider, Kirsten, Kemmitt, John, Hernandez-Gordillo, Victor, Yoon, Jun Young, Poyet, Mathilde, Alm, Eric J., Breault, David T., Trumper, David L., and Griffith, Linda G.

Abstract

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined p

Published
2024

2. An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii

Author

Zhang, Jianbo, primary, Huang, Yu-Ja, additional, Trapecar, Martin, additional, Wright, Charles, additional, Schneider, Kirsten, additional, Kemmitt, John, additional, Hernandez-Gordillo, Victor, additional, Yoon, Jun Young, additional, Poyet, Mathilde, additional, Alm, Eric J., additional, Breault, David T., additional, Trumper, David L., additional, and Griffith, Linda G., additional

Published
2024
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4. The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance

Author

Dall’Agnese, Alessandra, primary, Platt, Jesse M., additional, Zheng, Ming M., additional, Friesen, Max, additional, Dall’Agnese, Giuseppe, additional, Blaise, Alyssa M., additional, Spinelli, Jessica B., additional, Henninger, Jonathan E., additional, Tevonian, Erin N., additional, Hannett, Nancy M., additional, Lazaris, Charalampos, additional, Drescher, Hannah K., additional, Bartsch, Lea M., additional, Kilgore, Henry R., additional, Jaenisch, Rudolf, additional, Griffith, Linda G., additional, Cisse, Ibrahim I., additional, Jeppesen, Jacob F., additional, Lee, Tong I., additional, and Young, Richard A., additional

Published
2022
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5. The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance

Author

Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Physics, Dall’Agnese, Alessandra, Platt, Jesse M, Zheng, Ming M, Friesen, Max, Dall’Agnese, Giuseppe, Blaise, Alyssa M, Spinelli, Jessica B, Henninger, Jonathan E, Tevonian, Erin N, Hannett, Nancy M, Lazaris, Charalampos, Drescher, Hannah K, Bartsch, Lea M, Kilgore, Henry R, Jaenisch, Rudolf, Griffith, Linda G, Cisse, Ibrahim I, Jeppesen, Jacob F, Lee, Tong I, Young, Richard A, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Physics, Dall’Agnese, Alessandra, Platt, Jesse M, Zheng, Ming M, Friesen, Max, Dall’Agnese, Giuseppe, Blaise, Alyssa M, Spinelli, Jessica B, Henninger, Jonathan E, Tevonian, Erin N, Hannett, Nancy M, Lazaris, Charalampos, Drescher, Hannah K, Bartsch, Lea M, Kilgore, Henry R, Jaenisch, Rudolf, Griffith, Linda G, Cisse, Ibrahim I, Jeppesen, Jacob F, Lee, Tong I, and Young, Richard A

Abstract

AbstractInsulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches.

Published
2022

6. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids

Author

Below, Christopher R., primary, Kelly, Joanna, additional, Brown, Alexander, additional, Humphries, Jonathan D., additional, Hutton, Colin, additional, Xu, Jingshu, additional, Lee, Brian Y., additional, Cintas, Celia, additional, Zhang, Xiaohong, additional, Hernandez-Gordillo, Victor, additional, Stockdale, Linda, additional, Goldsworthy, Matthew A., additional, Geraghty, Joe, additional, Foster, Lucy, additional, O’Reilly, Derek A., additional, Schedding, Barbara, additional, Askari, Janet, additional, Burns, Jessica, additional, Hodson, Nigel, additional, Smith, Duncan L., additional, Lally, Catherine, additional, Ashton, Garry, additional, Knight, David, additional, Mironov, Aleksandr, additional, Banyard, Antonia, additional, Eble, Johannes A., additional, Morton, Jennifer P., additional, Humphries, Martin J., additional, Griffith, Linda G., additional, and Jørgensen, Claus, additional

Published
2021
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7. Coculture of primary human colon monolayer with human gut bacteria

Author

Zhang, Jianbo, primary, Hernandez-Gordillo, Victor, additional, Trapecar, Martin, additional, Wright, Charles, additional, Taketani, Mao, additional, Schneider, Kirsten, additional, Chen, Wen Li Kelly, additional, Stas, Eric, additional, Breault, David T., additional, Carrier, Rebecca L., additional, Voigt, Christopher A., additional, and Griffith, Linda G., additional

Published
2021
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13. Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

Author

Edington, Collin D., primary, Chen, Wen Li Kelly, additional, Geishecker, Emily, additional, Kassis, Timothy, additional, Soenksen, Luis R., additional, Bhushan, Brij M., additional, Freake, Duncan, additional, Kirschner, Jared, additional, Maass, Christian, additional, Tsamandouras, Nikolaos, additional, Valdez, Jorge, additional, Cook, Christi D., additional, Parent, Tom, additional, Snyder, Stephen, additional, Yu, Jiajie, additional, Suter, Emily, additional, Shockley, Michael, additional, Velazquez, Jason, additional, Velazquez, Jeremy J., additional, Stockdale, Linda, additional, Papps, Julia P., additional, Lee, Iris, additional, Vann, Nicholas, additional, Gamboa, Mario, additional, LaBarge, Matthew E., additional, Zhong, Zhe, additional, Wang, Xin, additional, Boyer, Laurie A., additional, Lauffenburger, Douglas A., additional, Carrier, Rebecca L., additional, Communal, Catherine, additional, Tannenbaum, Steven R., additional, Stokes, Cynthia L., additional, Hughes, David J., additional, Rohatgi, Gaurav, additional, Trumper, David L., additional, Cirit, Murat, additional, and Griffith, Linda G., additional

Published
2018
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17. Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Author

Belair, David G., primary, Whisler, Jordan A., additional, Valdez, Jorge, additional, Velazquez, Jeremy, additional, Molenda, James A., additional, Vickerman, Vernella, additional, Lewis, Rachel, additional, Daigh, Christine, additional, Hansen, Tyler D., additional, Mann, David A., additional, Thomson, James A., additional, Griffith, Linda G., additional, Kamm, Roger D., additional, Schwartz, Michael P., additional, and Murphy, William L., additional

Published
2014
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22. Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies

Author

Jorge Valdez, Cynthia L. Stokes, Matthew Dallas, Emily Geishecker, Michael Shockley, Linda G. Griffith, Matthew E. LaBarge, Murat Cirit, Christian Maass, Massachusetts Institute of Technology. Biotechnology Process Engineering Center, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Maass, Christian Alexander, LaBarge, Matthew E, Shockley, Michael J, Valdez Macias, Jorge Luis, Geishecker, Emily R, Griffith, Linda G, and Cirit, Murat

Subjects
0301 basic medicine, Biochemical Phenomena, Computer science, Science, Systems biology, Induced Pluripotent Stem Cells, Cell Culture Techniques, Computational biology, Article, 03 medical and health sciences, Nutrient, Humans, Tissue specific, Computer Simulation, Myocytes, Cardiac, Lactic Acid, Cells, Cultured, Ecosystem, Multidisciplinary, Extramural, Systems Biology, Microfluidic Analytical Techniques, In vitro, Culture Media, Intestines, Systems Integration, Glucose, 030104 developmental biology, Liver, Organ Specificity, Microtechnology, Medicine, Monitoring glucose, Caco-2 Cells, Energy Metabolism, HT29 Cells
Abstract

Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations., United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039), National Institutes of Health (U.S.) (U24TR001951), National Institutes of Health (U.S.). Microphysiological Systems Program (4-UH3-TR000496-03)

Published
2018
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23. Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Author

Jeremy J. Velazquez, Roger D. Kamm, Christine A. Daigh, James A. Thomson, Rachel L. Lewis, James A. Molenda, Tyler D. Hansen, Linda G. Griffith, William L. Murphy, Jordan A. Whisler, Vernella Vickerman, David A. Mann, David G. Belair, Michael P. Schwartz, Jorge Valdez, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Whisler, Jordan Ari, Kamm, Roger Dale, Valdez Macias, Jorge Luis, Velazquez, Jeremy J., and Griffith, Linda G.

Subjects
Vascular Endothelial Growth Factor A, Cancer Research, Matrigel, Tumor Necrosis Factor-alpha, Angiogenesis, Cellular differentiation, Induced Pluripotent Stem Cells, Endothelial Cells, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Cell Differentiation, Cell Biology, Fibroblasts, Biology, Article, Cell biology, Endothelial stem cell, Vascular endothelial growth factor A, Blood Vessels, Humans, CD146, Stem cell, Induced pluripotent stem cell
Abstract

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats., National Institutes of Health (U.S.) (NIH 1UH2 TR000506-01), National Institutes of Health (U.S.) (3UH2 TR000506-02S1), National Institutes of Health (U.S.) (T32 HL007936-12), National Institutes of Health (U.S.) (RO1 HL093282), National Institutes of Health (U.S.) (R21 EB016381-01)

Published
2014
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