Nicholas Bolden

Scholar: Nicholas Bolden

 Nicholas Bolden

 Major: Molecular Microbiology and Immunology

Faculty Mentors: Dr. Dean Burkin

Research Topic: α7 Integrin Enhancing Small Molecule Prevents Muscle Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy

Abstract: Duchenne Muscular Dystrophy (DMD) is a X-linked, musculoskeletal disorder caused by mutations in the dystrophin gene. These mutations cause a loss of dystrophin protein, which is a vital component in the dystrophin glycoprotein complex (DGC). The DGC connects intracellular actin filaments to the extracellular matrix (ECM) and provides the muscle fibers protection during muscle activity. Without the dystrophin gene, the muscle will degrade gradually and this eventually leads to serious myopathy. The α7β1 integrin is a laminin-binding partner in the ECM that attaches many of the same proteins as the dystrophin gene. Previous studies have demonstrated the upregulation of the α7β1 integrin improved muscle functioning in mdx mice, which is the mouse model of DMD. A high throughput screen was used to identify α7 enhancing small molecules. One of the compounds identified from the screen, SU9516, was shown to increase production of the α7β1 integrin and improve muscle functioning in mdx mice. An analog of the SU9516 was also identified as a small molecule capable of increasing production of the α7β1 integrin, and it also improves muscle functioning in mdx mice at a faster rate than its parent small molecule. It was also distributed at a lower dosage compared to the SU9516, and the small molecule itself is already FDA approved. The goal of this research project is to identify whether the treatments for the mdx mice could be taken weekly rather than daily. The methods of dissection, cryo-sectioning, immunofluorescence, and Western blotting will be used to determine whether weekly treatments are as effective as the daily treatments seen in the previous studies using the small molecule. Preliminary results of the weekly treatments will be discussed.

New Scholar: 2017 cohort

Graduating with a Baccalaureate Degree: 2018