The Kemaladewi Lab is interested in studying neuromuscular pathology and the development of therapeutic genetics for rare diseases.
Interventional genomics in rare diseases
A disease is defined as rare when it affects <200,000 people in the US. Although one rare disease may affect a handful of individuals, the opportunities to have an immediate clinical impact and generate new scientific knowledge make the study of rare genetic conditions greatly valuable and endlessly rewarding. To this end, genome engineering technology has emerged as a powerful tool in the study of rare disease and therapeutic development (PMID: 2668675).
We have previously utilized CRISPR/Cas9 technology to correct an underlying mutation (PMID: 28714989) and upregulate a compensatory gene (PMID: 31341277) in LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD). We will further evaluate the safety and efficacy of these strategies, with the goal of moving them closer to clinical applications.
Interplay between skeletal muscles and nervous systems in rare diseases
Neuromuscular disorders primarily affect skeletal muscles; however, there is a clear involvement and contribution of tissues beyond skeletal muscles to the clinical heterogeneity. The lack of functional LAMA2 in LAMA2-CMD leads to myopathy and peripheral neuropathy; yet, the latter remains underexplored in terms of basic etiology and therapeutic development. We use CRISPR activation to develop a novel patient-relevant myelination models to study the origin and progression of peripheral neuropathy in LAMA2-CMD.
Similarly, many neurological disorders are characterized by skeletal muscle abnormalities that are understudied. Patients with Snyder-Robinson syndrome (SRS), a rare neurological disease caused by shortage of polyamines, exhibit low muscle mass. Interestingly, we previously found alteration of polyamine metabolism in dystrophic muscle (PMID: 29566247). To precisely understand the role of polyamine in muscle growth and diseases, we apply our expertise in muscle regeneration and physiology to characterize skeletal muscle abnormality in a novel SRS mouse model.
Affiliated Faculty and Staff
- Dwi U. Kemaladewi, PhD - Principal Investigator
- Annie I. Arockiaraj, MS - PhD Student
- Jia Qi Cheng Zhang, MSc - PhD Student
- Marie Johnson, BSc - Lab Manager
- Oluwaseun Akinyele, PhD - Postdoctoral Associate
- Anushe Munir, MS - Research Technician