Date Approved

3-30-2026

Embargo Period

3-30-2026

Document Type

Dissertation

Degree Name

Ph.D. Cell and Molecular Biology

Department

Biological and Biomedical Sciences

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

James M. Holaska, Ph.D.

Committee Member 1

Darren Boehning, Ph.D.

Committee Member 2

Valerie J. Carabetta, Ph.D.

Committee Member 3

Amanda Fakira, Ph.D.

Committee Member 4

Karen L. Reddy, Ph.D.

Keywords

Emerin;Emery-Dreifuss Muscular Dystrophy;LEM;Myogenic Differentiation;Nuclear Lamina

Disciplines

Biochemistry, Biophysics, and Structural Biology | Life Sciences | Molecular Biology

Abstract

The nucleus harbors genetic material encapsulated by the nuclear envelope which is composed of an inner and outer nuclear membrane. The establishment and organization of chromatin at the INM is essential for cell fate during the differentiation program. Integral INM proteins are responsible for chromatin organization at the nuclear envelope. Emerin is a highly conserved type II integral INM protein with roles in chromatin organization, cell signaling, and nuclear structure. Mutations in the emerin gene cause Emery Dreifuss Muscular Dystrophy 1 (EDMD1). Emerin is ubiquitously expressed, but loss of emerin function affects specifically skeletal muscle and cardiac tissue. The precise mechanisms driving EDMD1 remain to be elucidated, but failure to repair skeletal muscle likely contributes to its pathogenesis. Previous work suggested emerin may participate in myogenic progenitor differentiation during skeletal muscle regeneration, but how emerin regulates myogenic differentiation remains poorly understood. In this dissertation, we identified two new emerin binding partners that likely contribute to higher order chromatin organization at the nuclear envelope. We performed a multi-omic analysis to investigate expression profiles and chromatin organization of differentiating myogenic progenitors expressing wildtype emerin, EDMD1 emerin mutations, or lacking emerin entirely to assess emerin’s role in transcriptional reprogramming. Lastly, we utilized lipid nanoparticles bearing emerin mRNA to rescue myogenic differentiation of emerin-null myogenic progenitor cells, as a proof-of-principle for a therapeutic approach.

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