Publications

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64 Publications visible to you, out of a total of 64
Wnt signaling modulates mechanotransduction in the epidermis to drive hair follicle regeneration.

Abstract (Expand)

Most wounds form scars without hair follicles. However, in the wound-induced hair neogenesis (WIHN) model of skin regeneration, wounds regenerate hair follicles if tissue rigidity is optimal. Although … WIHN depends on Wnt signaling, whether Wnt performs a mechanoregulatory role that contributes to regeneration remains uncharacterized. Here, we demonstrate that Wnt signaling affects mechanosensitivity at both cellular and tissue levels to drive WIHN. Atomic force microscopy revealed an attenuated substrate rigidity response in epidermal but not dermal cells of healing wounds. Super-resolution microscopy and nanoneedle probing of intracellular compartments in live human keratinocytes revealed that Wnt-induced chromatin remodeling triggers a 10-fold drop in nuclear rigidity without jeopardizing the nucleocytoskeletal mechanical coupling. Mechanistically, Wnt signaling orchestrated a massive reorganization of actin architecture and recruited adherens junctions to generate a mechanical syncytium-a cohesive contractile unit with superior capacity for force coordination and collective durotaxis. Collectively, our findings unveil Wnt signaling's mechanoregulatory role that manipulates the machinery of mechanotransduction to drive regeneration.

Authors: A. S. W. Oak, A. Bagchi, M. J. Brukman, J. Toth, J. Ford, Y. Zheng, A. Nace, R. Yang, J. C. Hsieh, J. E. Hayden, G. Ruthel, A. Ray, E. Kim, V. B. Shenoy, G. Cotsarelis

Date Published: 21st Feb 2025

Publication Type: Journal Article

Cross-species transcriptomics translation reveals a role for the unfolded protein response in Mycobacterium tuberculosis infection.

Abstract

Not specified

Authors: Krista M. Pullen, Ryan Finethy, Seung-Hyun B. Ko, Charlotte J. Reames, Christopher M. Sassetti, Douglas A. Lauffenburger

Date Published: 15th Feb 2025

Publication Type: Journal Article

Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes

Abstract

Not specified

Authors: Andrew W. Simonson, Joseph J. Zeppa, Allison N. Bucsan, Michael C. Chao, Supriya Pokkali, Forrest Hopkins, Michael R. Chase, Andrew J. Vickers, Matthew S. Sutton, Caylin G. Winchell, Amy J. Myers, Cassaundra L. Ameel, Ryan J. Kelly, Ben Krouse, Luke E. Hood, Jiaxiang Li, Chelsea C. Lehman, Megha Kamath, Jaime Tomko, Mark A. Rodgers, Rachel Donlan, Harris Chishti, H. Jacob Borish, Edwin Klein, Charles A. Scanga, Sarah M. Fortune, Philana Ling Lin, Pauline Maiello, Mario Roederer, Patricia A. Darrah, Robert A. Seder, JoAnne L. Flynn

Date Published: 1st Feb 2025

Publication Type: Journal Article

Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis.

Abstract (Expand)

Lung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts and extracellular matrix, as well as vascular remodeling. The crosstalk … between myofibroblasts and vasculature is poorly understood, with conflicting reports on whether angiogenesis and vessel density are increased or decreased in lung fibrosis. We developed a microphysiological system that recapitulates the pathophysiology of lung fibrosis and disentangles myofibroblast-vascular interactions. Lung myofibroblasts maintained their phenotype in 3D without exogenous TGF-beta and displayed anti-angiogenic and anti-vasculogenic activities when cultured with endothelial cells in a microfluidic device. These effects, including decreased endothelial sprouting, altered vascular morphology, and increased vascular permeability, were mediated by increased TGF-beta1 and reduced VEGF secretion. Pharmacological interventions targeting these cytokines restored vascular morphology and permeability, demonstrating the potential of this model to screen anti-fibrotic drugs. This system provides insights into myofibroblast-vascular crosstalk in lung fibrosis and offers a platform for therapeutic development.

Authors: E. Cambria, A. Blazeski, E. C. Ko, T. Thai, S. Dantes, D. A. Barbie, S. E. Shelton, R. D. Kamm

Date Published: 14th Jan 2025

Publication Type: Journal Article

Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.

Abstract (Expand)

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the … human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains. Instead, packing domains exist across a structure-function life cycle that couples heterochromatin and transcription in situ, explaining how heterochromatin enzyme inhibition can produce a paradoxical decrease in transcription by destabilizing domain cores. Applied to development and aging, we show the pairing of heterochromatin and transcription at myogenic genes that could be disrupted by nuclear swelling. In sum, packing domains represent a foundation to explore the interactions of chromatin and transcription at the single-cell level in human health.

Authors: L. M. Almassalha, M. Carignano, E. P. Liwag, W. S. Li, R. Gong, N. Acosta, C. L. Dunton, P. C. Gonzalez, L. M. Carter, R. Kakkaramadam, M. Kroger, K. L. MacQuarrie, J. Frederick, I. C. Ye, P. Su, T. Kuo, K. I. Medina, J. A. Pritchard, A. Skol, R. Nap, M. Kanemaki, V. Dravid, I. Szleifer, V. Backman

Date Published: 10th Jan 2025

Publication Type: Journal Article

Confined cell migration along extracellular matrix space in vivo.

Abstract (Expand)

Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. … Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.

Authors: O. Chepizhko, J. M. Armengol-Collado, S. Alexander, E. Wagena, B. Weigelin, L. Giomi, P. Friedl, S. Zapperi, C. A. M. La Porta

Date Published: 7th Jan 2025

Publication Type: Journal Article

High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways

Abstract

Not specified

Authors: Joshua M. Peters, Edward B. Irvine, Mohau S. Makatsa, Jacob M. Rosenberg, Marc H. Wadsworth, Travis K. Hughes, Matthew S. Sutton, Sarah K. Nyquist, Joshua D. Bromley, Rajib Mondal, Mario Roederer, Robert A. Seder, Patricia A. Darrah, Galit Alter, Chetan Seshadri, JoAnne L. Flynn, Alex K. Shalek, Sarah M. Fortune, Bryan D. Bryson

Date Published: 2025

Publication Type: Journal Article

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