Tokunbor A. Lawal, PhD, FNP-BC
Independent Research Scholar
Division of Intramural Research
Topic: Our research activities encourage the development of preclinical translational models of congenital myopathies related to skeletal muscle excitation-contraction coupling defects to identify opportunities for therapeutic interventions.
Issue: Congenital myopathies (CM) are a heterogeneous group of early-onset neuromuscular disorders that primarily present with hypotonia, muscle weakness that include facial muscles, and often respiratory involvement. Adult-onset cases have also been described. They are frequently associated with significant lifelong morbidities that are severely disabling and can result in premature mortality. They have historically been classified based on muscle biopsy findings. Over 20 genes have been linked with CM. A key area of pathology in CM are the skeletal muscle triads that control excitation-contraction coupling. There is no approved treatment for this group of debilitating diseases. CM constitutes a group of rare (orphan) diseases (pooled prevalence: 1.5/100,000). A significant portion of genetic variations identified in individuals with CM are classified as variants of uncertain significance (VUS). While pathogenic variants have a clinically confirmed association with increased disease risk, VUS results do not. The functional consequence of harboring a VUS is not known and not clearly linked to disease. A VUS can be reclassified through functional assays that characterize the impact of such genetic variations on protein function.
Impact: The Lawal Lab aims to functionally characterize genetic VUS associated with skeletal muscle excitation-contraction coupling disorders using relevant, reliable, and cost-effective preclinical models. These preclinical models allow us to screen promising therapeutic compounds and elucidate the patho-mechanisms that can be targeted for therapeutic interventions in clinical trials. Our research is focused on reducing and ultimately eliminating the health inequities facing individuals with CM without approved treatments and identify effective approaches to improve the health and quality of life of individuals with this rare and neglected group of genetic disorders.
Dr. Lawal is currently developing his clinical protocols and has collaborated as an associate investigator on the following:
- NCT04141670: S 48168 (ARM 210) for the Treatment of RYR1-Related Myopathies (RYR1-RM) (20-N-0005)
- NCT02362425: Antioxidant Therapy in RYR1-Related Congenital Myopathy (RYR1) (15-NR-0072)
- Serves as an officer within the United States Public Health Service (USPHS)
- Became an NIH Independent Research Scholar in 2019
- Joined NINR in 2017 as a post-doctoral fellow with the Neuromuscular Symptoms Unit where he served as an Associate Investigator in a Phase I/II clinical trial on the efficacy of N-acetylcysteine in decreasing oxidative stress and improving physical endurance in RYR1-RM
- 2021 NINR Director’s Service Award
- 2019 NIH Independent Research Scholar Award
- 2011 NIH Graduate Partnerships Program (GPP) Award
- PhD in Nursing, Johns Hopkins University, Baltimore, Maryland
- MS in Family Nurse Practitioner, Marymount University, Arlington, Virginia
- BS in Nursing, Georgetown University, Washington, DC
- BS in Biology, University of Maryland, College Park, Maryland
- Family Nurse Practitioner
- Lawal, T.A. Central Core Disease: National Organization for Rare Disorders (NORD) Rare Disease Database. (2022, February 18). https://rarediseases.org/rare-diseases/central-core-disease/.
- Lawal, T.A., Patankar, A., Todd, J.J., et al. Ryanodine receptor 1-related myopathies: Semi-automated quantification of intramuscular fatty infiltration from T1-weighted MRI. Journal of Neuromuscular Diseases. 2021. doi: 10.3233/JND-200549.
- Lawal, T.A., Wires, E.S., Terry, N.L., et al. Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019. Orphanet Journal of Rare Diseases. 2020. doi: 10.1186/s13023-020-01384-x.
- Lawal, T.A., Todd, J.J., Elliott, J.S., et al. Assessing Motor Function in Congenital Muscular Dystrophy Patients using Accelerometry. Neuroscience Nursing. 2020.
- Lawal, T.A., Todd, J.J., & Meilleur, K.G. Ryanodine receptor 1-related disorders: a historical perspective and proposal for a unified nomenclature. Skeletal Muscle. 2020. doi: 10.1186/s13395-020-00243-4.
- Todd, J.J., Lawal, T.A., Witherspoon, J.W., et al. A randomized controlled trial of N-acetylcysteine therapy for RYR1-related myopathies. Neurology. 2020. doi: 10.1212/WNL.0000000000008872.
- Lawal, T.A., Todd, J.J., & Meilleur, K.G. Ryanodine receptor-1 related myopathies: diagnostic and therapeutic approaches. Neurotherapeutics. 2018. doi: 10.1007/s13311-018-00677-1.
- Lawal, T.A., Lewis, K.L., Johnston, J.J., et al. Disclosure of Cardiac Variants of Uncertain Significance Results in an Exome Cohort. Clinical Genetics. 2018. doi: 10.1111/cge.13220.
- Kuo, A., Todd, J.J., Witherspoon, J.W., Lawal, T.A., et al. Reliability and validity of self-report questionnaires as indicators of fatigue in RYR1-related disorders. J Neuromuscular Diseases. 2019; 6(1): 133-141. doi: 10.3233/JND-180335.
- Todd, J.J., Razaqyar, M.S., Witherspoon, J.W., Lawal, T.A., et al. Novel variants in individuals with RYR1-related congenital myopathies: genetic, laboratory, and clinical findings. Frontiers in Neurology. 2018; 9: 118. doi: 10.3389/fneur.2018.00118.
- Lewis, K.L., Miller, I., Lawal, T.A., et al. Health Behaviors Amongst Unaffected Participants Following Receipt of Variants of Uncertain Significance in Cardiomyopathy-Associated Genes. Genetics in Medicine. 2018. doi: 10.1038/s41436-018-0083-8.
For Dr. Lawal's full bibliography, please visit ORCID.or