I first came to work at the Jackson Laboratory as a college intern in the Fall of 2011. I had the privilege of being mentored by Dr. Kevin Seburn in the Lab of Dr. Robert Burgess. Our research focused primarily on Neurodegenerative diseases and defects within the neuromuscular system.
Following graduation, I joined the lab of Dr. Cathleen Lutz and furthered my studies of diseases of the neuromuscular system, specifically Spinal Muscular Atrophy and Duchenne's Muscular Dystrophy.
I have recently expanded my research interests, and have joined Dr. Laura Reinholdt in the study of the mammalian genome. Presently, I study a variety of developmental mutations that give rise to genomic instabilities, which have adverse affects on chromosome segregation, germline development, cell division, and bone development.
Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan-null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them with the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared with their respective control strains at multiple time points between 6 and 52 weeks of age. Skeletal and cardiac muscle function, inflammation, regeneration, histology and biochemistry were characterized. We found that D2-mdx mice showed significantly reduced skeletal muscle function as early as 7 weeks and reduced cardiac function by 28 weeks, suggesting that the disease phenotype is more severe than in B10-mdx mice. In addition, D2-mdx mice showed fewer central myonuclei and increased calcifications in the skeletal muscle, heart and diaphragm at 7 weeks, suggesting that their pathology is different from the B10-mdx mice. The new D2-mdx model with an earlier onset and more pronounced dystrophy phenotype may be useful for evaluating therapies that target cardiac and skeletal muscle function in dystrophin-deficient mice. Our data align the D2-mdx with Duchenne muscular dystrophy patients with the LTBP4 genetic modifier, making it one of the few instances of cross-species genetic modifiers of monogenic traits.