P.WadsworthPaul Wadsworth
Year in Program: GY4
Undergrad University: Loyola University Chicago
Mentor: Fernanda Laezza, MD, PhD
Graduate Program: Biochemistry and Molecular Biology

Paul Wadsworth

Brain circuitry is complex and requires regulatory stability to maintain healthy neural plasticity and excitability. Minor fluctuations in signaling pathways lead to significant aberrations in these circuits, giving rise to clinical manifestations of neuropsychiatric disease such as schizophrenia, depression, and Alzheimer’s disease. The precise pathways involved in neuropsychiatric disorders must be resolved to understand how disease arises, and to subsequently design modulators capable of stabilizing neuronal circuitry. Voltage-gated sodium (Nav) channels form the basis of electrical excitability in these circuits, in particular those located at the axonal initial segment (AIS), the site of action potential initiation. These ion channels form highly regulated macromolecular complexes, and their biophysical properties are modulated by fibroblast growth factor 14 (FGF14) and glycogen synthase kinase 3-beta (GSK3-beta), an enzyme implicated in nearly all neuropsychiatric disorders. I am interested in exploring how changes in inflammatory and regenerative cell signaling events seen in disease contribute to the dysregulation of sodium channel complexes. I use both biophysical and cell-based techniques to study the protein:protein interactions between FGF14, Nav1.6, and GSK3-beta, and aim to understand how these interactions change based on activation of either the TNF receptor (TNFR1) or the receptor for BDNF, TrkB.
  • Dr. Robert Harrison, MD, Memorial MD/PhD Scholarship (2017)
  • T32 in Aging and Health Disparities Fellow
  • Dr. Harrison, MD, Memorial MD/PhD Endowment Scholarship
  • Blocker Scholarship
  • Lichti CF, Mostovenko E, Wadsworth PA, Pettitt BM, Sulman EP, Wang Q, et al. Systematic Identification of Single Amino Acid Polymorphisms in Glioma Stem Cell-Derived Chromosome 19 Proteins. J Proteome Reseach. 2015;14: 778–786. doi:10.1021/pr500810g
  • Di Re J, Wadsworth PA, Laezza F. Intracellular Fibroblast Growth Factor 14: Emerging Risk Factor for Brain Disorders. Front Cell Neurosci. 2017;11: 1–7. doi:10.3389/fncel.2017.00103
  • Wadsworth PA, Chen N, Markides KS, Downer B. Mobility and Balance Limitations are Associated with Increased Cognitive Decline in Elderly Mexican Americans. Proceedings of the UTMB 21st Annual Forum on Aging. (University of Texas Medical Branch, Galveston, TX), 2017. *Best Student Poster in Health Disparities Research.
  • Wadsworth PA, Singh AK, Sepuru KM, Rajarathnam K, Laezza F. GSK3β is a new molecular determinant of neuronal excitability. Proceedings of the 47th annual Society for Neuroscience meeting. (Washington, DC), 2017.
  • Wadsworth PA, Singh AK, and Laezza F. Modulation of FGF14 and Nav1.6 by GSK3β. Proceedings of the 22nd SCSB Structural Biology Symposium (University of Texas Medical Branch, Galveston, TX), 2017.
  • Wadsworth PA, Singh AK, and Laezza F. Structural mapping of the FGF14:GSK3β complex. Proceedings of the Annual Biophysical Society Meeting (New Orleans, LA), 2017.
  • Wong J, Wadsworth PA, Singh AK, Ali SR, and Laezza F. Virtual screening in search of allosteric modulators of Nav1.1 channels. Proceedings of the Annual Biophysical Society Meeting (New Orleans, LA), 2017.
  • Wadsworth PA, Di Re J, Ali SR, and Laezza F. Interrogation of Single Nucleotide Polymorphisms in FGF14. American Physician Scientist Association Regional Conference (University of Texas Medical Branch, Galveston, TX), 2017.
  • Di Re J, Wadsworth PA, and Laezza F. Interrogation of Single Nucleotide Polymorphisms in Genes Associated with Schizophrenia. Neuroscience Graduate Program Retreat (University of Texas Medical Branch, Galveston, TX), 2016.
  • Di Re J, Wadsworth PA, and Laezza F. Genetic variations of FGF14 in neuropsychiatric disorders. Precision Genome Editing Workshop (Rice University, Houston, TX), 2016.