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62 Publications visible to you, out of a total of 62
Systematic deconstruction of myeloid cell signaling in tuberculosis granulomas reveals IFN-γ, TGF-β, and time are associated with conserved myeloid diversity

Abstract

Not specified

Authors: Joshua M. Peters, Hannah P. Gideon, Travis K. Hughes, Cal Gunnarson, Pauline Maiello, Douaa Mugahid, Sarah K. Nyquist, Joshua D. Bromley, Paul C. Blainey, Beth F. Junecko, Molly L. Nelson, Douglas A. Lauffenburger, Philana Ling Lin, JoAnne L. Flynn, Alex K. Shalek, Sarah M. Fortune, Joshua T. Mattila, Bryan D. Bryson

Date Published: 1st May 2024

Publication Type: Journal

Age and sex influence antibody profiles associated with tuberculosis progression.

Abstract

Not specified

Authors: Leela R. L. Davies, Chuangqi Wang, Pia Steigler, Kathryn A. Bowman, Stephanie Fischinger, Mark Hatherill, Michelle Fisher, Stanley Kimbung Mbandi, Miguel Rodo, Tom H. M. Ottenhoff, Hazel M. Dockrell, Jayne S. Sutherland, Harriet Mayanja-Kizza, W. Henry Boom, Gerhard Walzl, Stefan H. E. Kaufmann, Elisa Nemes, Thomas J. Scriba, Douglas Lauffenburger, Galit Alter, Sarah M. Fortune

Date Published: 24th Apr 2024

Publication Type: Journal

CD8+ lymphocytes are critical for early control of tuberculosis in macaques

Abstract

Not specified

Authors: Caylin G. Winchell, Sarah K. Nyquist, Michael C. Chao, Pauline Maiello, Amy J. Myers, Forrest Hopkins, Michael Chase, Hannah P. Gideon, Kush V. Patel, Joshua D. Bromley, Andrew W. Simonson, Roisin Floyd-O’Sullivan, Marc Wadsworth, Jacob M. Rosenberg, Rockib Uddin, Travis Hughes, Ryan J. Kelly, Josephine Griffo, Jaime Tomko, Edwin Klein, Bonnie Berger, Charles A. Scanga, Joshua Mattila, Sarah M. Fortune, Alex K. Shalek, Philana Ling Lin, JoAnne L. Flynn

Date Published: 16th Oct 2023

Publication Type: Journal

Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk.

Abstract (Expand)

BACKGROUND: The human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone-mediated … signaling may be linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. METHODS: We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. FINDINGS: Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during interleukin 1B (IL1B)-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. CONCLUSIONS: Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases. FUNDING: This work was supported by The John and Karine Begg Foundation, the Manton Foundation, and NIH U01 (EB029132).

Authors: J. S. Gnecco, A. Brown, K. Buttrey, C. Ives, B. A. Goods, L. Baugh, V. Hernandez-Gordillo, M. Loring, K. B. Isaacson, L. G. Griffith

Date Published: 11th Aug 2023

Publication Type: Journal

Humoral correlates of protection against <i>Mycobacterium tuberculosis</i> following intravenous Bacille Calmette-Guérin vaccination in rhesus macaques.

Abstract

Not specified

Authors: Edward B. Irvine, Patricia A. Darrah, Shu Wang, Chuangqi Wang, Ryan P. McNamara, Mario Roederer, Robert A. Seder, Douglas A. Lauffenburger, JoAnne L. Flynn, Sarah M. Fortune, Galit Alter

Date Published: 2nd Aug 2023

Publication Type: Journal

Impact of Fibrinogen, Fibrin Thrombi, and Thrombin on Cancer Cell Extravasation Using In Vitro Microvascular Networks.

Abstract (Expand)

A bidirectional association exists between metastatic dissemination and the hypercoagulable state associated with many types of cancer. As such, clinical studies have provided evidence that markers … associated with elevated levels of coagulation and fibrinolysis correlate with decreased patient survival. However, elucidating the mechanisms underpinning the effects of different components of the coagulation system on metastasis formation is challenging both in animal models and 2D models lacking the complex cellular interactions necessary to model both thrombosis and metastasis. Here, an in vitro, 3D, microvascular model for observing the formation of fibrin thrombi is described, which is in turn used to study how different aspects of the hypercoagulable state associated with cancer affect the endothelium. Using this platform, cancer cells expressing ICAM-1 are shown to form a fibrinogen-dependent bridge and transmigrate through the endothelium more effectively. Cancer cells are also demonstrated to interact with fibrin thrombi, using them to adhere, spread, and enhance their extravasation efficiency. Finally, thrombin is also shown to enhance cancer cell extravasation. This system presents a physiologically relevant model of fibrin clot formation in the human microvasculature, enabling in-depth investigation of the cellular interactions between cancer cells and the coagulation system affecting cancer cell extravasation.

Authors: E. Angelidakis, S. Chen, S. Zhang, Z. Wan, R. D. Kamm, S. E. Shelton

Date Published: 28th Jul 2023

Publication Type: Journal

Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes.

Abstract (Expand)

Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes … probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.

Authors: Z. Gong, K. van den Dries, R. A. Migueles-Ramirez, P. W. Wiseman, A. Cambi, V. B. Shenoy

Date Published: 22nd May 2023

Publication Type: Journal

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