Surgery, Science, And The Models That Fall In Between: A foray into intra-cavitary adhesions

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Investigative Medicine

First Advisor

Flavell, Richard

Abstract

Physiologic fibrosis is a necessary feature of multicellular life; however, when pathologic fibrosis ensues no organ is safe from the accumulation of extracellular matrix proteins. To study fibrosis and other diseases, there is a need for improved animal models that better recapitulate the disease in humans. Here, we use surgical principles to develop, describe, and validate four novel mouse models to explore two major tissue types: fibrosis and secondary lymphoid organs. We employ these models in fibrosis to identify a vast world of mesenchymal heterogeneity. We show proof of principle for the biologic process of convergent plasticity—a phenomenon in which distinct, steadystate adult lineages transdifferentiate into a transcriptionally identical daughter population, irrespective of ontogeny. We identify a subset of cells that arise through convergent plasticity, which are necessary in the development and maintenance of thick fibrotic adhesions. Through this work, we hope there comes a respite from the vicious cycle of adhesions disruption and re-formation.

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