Matrix Biology and Engineering Lab

SEMA7a primes integrin α5β1 engagement instructing fibroblast mechanotransduction, phenotype and transcriptional programming

Fri, 07 Jul 2023 06:57:49 -0700

SEMA7a primes integrin α5β1 engagement instructing fibroblast mechanotransduction, phenotype and transcriptional programming.

Hu P , Miller AE , Yeh CR , Bingham GC , Civelek M , Barker Read More

Professor Dan Ababayehu

Mon, 01 May 2023 06:07:53 -0700

Congrats to Dan for starting his new position today as Assistant Professor of Biomedical Engineering at the University of Virginia. We were lucky to have him in the lab for last number of years and we at UVA are very lucky to have Dan joining our faculty. I'm extremely proud of Dan's accomplishments during his postdoc. He was a K99/R00 recipient, so he has some nice momentum.

Good luck on getting those grants Dan!

Special issue of Matrix Biology Published!!

Thu, 13 Aug 2020 05:34:44 -0700

Tom Barker and Merry Lindsey co-edit special issue in Matrix Biology on fibroblasts and fibrosis

The Matrix Biology and Engineering Lab participated in a number of key articles published recently in the Special Issue of Matrix Biology on Fibroblasts: The arbiters of matrix remodeling.

Grace Bingham, PhD candidate, teamed up with our friend Alexandra Naba from Univ of Illinois - Chicago and wrote an outstanding article on Spatialomics. These omics-level methods that enable tissue localization of signals are the wave of the future as we not only try to grapple with our increasing awareness of cellular heterogeneity but appreciate the dominant role microenvironment has on directing geneotypes and phenotypes of cells. This is never more important than for the fibroblast; the cell type that is perhaps the most "impressionable". Single cell approaches have really demonstrated that pathogenic fibroblasts are not some unique clonal population of bad actors, but rather are a function of their environment...

We also teamed up with Shayn Peirce-Cottler at UVA to review and highlight the emergence of Agent-Based Modeling (ABM) in understanding and predicting lung remodeling due to fibroblasts. ABM has the potential to uncover highly orchestrated emergent behaviors in tissue repair in increasingly complex microenvironments. The ability to model many cell phenotypes and their interactions with matrix queues and other cell types by setting rules and allowing the agents to 'do their thing' has such great potential to...Read More

MBEL Undergraduate researchers score National Awards

Wed, 08 Apr 2020 07:13:05 -0700

Two MBEL Undergraduates (one current and one alum) have been awarded the NSF's Graduate Research Fellowship to extend their studies in Graduate School. Both are pursuing their PhD and while Jacqueline (top) has been conducting her PhD research in the lab of Carlos Aguilar at the University of Michigan, Allison (bottom) is still undetermined about her future destination for graduate school.

We wish them the best of luck in their future pursuits! Thanks for representing the lab so well and helping to pave the way for future students' success in MBEL.

Citrullination of fibronectin alters integrin clustering and focal adhesion stability promoting stromal cell invasion

Sun, 29 Sep 2019 20:06:48 -0700

Congratulations to Dr. Nicosia!

Mon, 29 Apr 2019 19:56:42 -0700

Drew Miller joins MBEL

Sat, 15 Dec 2018 20:10:22 -0800

Drew Miller joins UVA BME program and the Matrix Biology and Engineering Lab following a fall term of lab rotations. Drew comes from Pam Kreger's lab at UWisc BME. Thanks Pam for training such a great student!

Dr. Dan Abebayehu scores 11% on F32 application

Thu, 13 Dec 2018 06:13:14 -0800

Dan is proposing to study how inflammatory cells (macrophages and neutrophils) impact the emergence of pro-fibrotic and mechanotransductively altered fibroblast supopulations.

Vince Fiore publishes in JCI Insights

Thu, 18 Oct 2018 17:51:35 -0700

Fiore VF, Tran C, Xu W, Sulchek T, White ES, Wong S, Hagood JS, Barker TH. avb3 integrin engagement of soft nonlinearly elastic ECM drives myofibroblast activation and progressive fibrosis. JCI Insights 3(2):e97597, 2018.

Abstract:

Fibrosis is characterized by persistent deposition of extracellular matrix (ECM) by fibroblasts. Fibroblast mechanosensing of a stiffened ECM is hypothesized to drive the fibrotic program; however, the spatial distribution of ECM mechanics and their derangements in progressive fibrosis are poorly characterized. Importantly, fibrosis presents with significant histopathological heterogeneity at the microscale. Here, we report that fibroblastic foci (FF), the regions of active fibrogenesis in idiopathic pulmonary fibrosis (IPF), are surprisingly of similar modulus as normal lung parenchyma and are nonlinearly elastic. In vitro, provisional ECMs with mechanical properties similar to those of FF activate both normal and IPF patient–derived fibroblasts, whereas type I collagen ECMs with similar mechanical properties do not. This is mediated, in part, by α_vβ₃ integrin engagement and is augmented by loss of expression of Thy-1, which regulates α_vβ₃integrin avidity for ECM. Thy-1 loss potentiates cell contractility-driven strain stiffening of provisional ECM in vitro and causes elevated α_vβ₃ integrin activation, increased fibrosis, and greater mortality following fibrotic lung injury in vivo. These data suggest a central role for α_vβ₃ integrin and provisional ECM in overriding mechanical cues that normally impose quiescent phenotypes, driving progressive fibrosis through physical stiffening of the fibrotic niche.

Grace Bingham joins MBEL

Wed, 29 Aug 2018 20:09:11 -0700