Date Approved
2-1-2025
Embargo Period
3-24-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.)
Department
Cell Biology and Neuroscience
College
Rowan-Virtua School of Translational Biomedical Engineering & Sciences
Advisor
Vincent Manna, PhD
Committee Member 1
Salvatore Caradonna, PhD
Committee Member 2
Susan Muller-Weeks, PhD
Committee Member 3
Ronald E. Ellis, PhD
Committee Member 4
Katharine Milani, PhD
Committee Member 5
Valerie Carabetta, PhD
Disciplines
Biochemistry | Biochemistry, Biophysics, and Structural Biology | Life Sciences
Abstract
The vitamin D endocrine system is responsible for the regulation of many biological processes including bone metabolism, calcium homeostasis, cell proliferation and cell differentiation. Alterations to the vitamin D signaling pathway are associated with several diseases including bone diseases, diabetes, cardiovascular diseases, autoimmune diseases, and cancer. Vitamin D precursors are chemically modified to become the biologically active hormone, calcitriol. Calcitriol binds to the vitamin D receptor (VDR), a member of the nuclear hormone receptor (NHR) superfamily. VDR forms a heterodimer with retinoid X receptor (RXR) and together they bind to promoters containing vitamin D response elements (VDREs) to activate transcription of target genes. Other NHRs have been shown to be post-translationally modified that can either increase or decrease their transcriptional output through alterations in protein-protein or protein-DNA interactions. I have generated evidence that two lysines on VDR are likely to be targets of acetylation, and alterations to lysine deacetylase activity impacts VDR transcriptional output through changes in co-activator and co-repressor binding. Together, these data suggest a novel way for the cell to modulate the response of VDR to available vitamin D.
Recommended Citation
Dwyer, Shannon, "Inhibition of Lysine Deacetylase Activity Impacts Formation of the Vitamin D Receptor Activation Complex" (2025). Theses and Dissertations. 3333.
https://rdw.rowan.edu/etd/3333
