Ph.D., Neuroscience, University of Florida, Gainesville, Florida
B.S., Cell Biology, University of Kansas, Lawrence, Kansas
Research Synopsis: The Sherry lab explores the organization of synapses in health and disease. The lab focuses on the functional roles of lipids and synaptic adhesion proteins in organizing synaptic structure and transmission in the developing, healthy, and neurodegenerating brain and retina. Methods focus primarily on imaging approaches including fluorescent, confocal, super-resolution, and electron microscopy methods.
Office Phone: (405) 271-8001 ext. 45514
Fax Number: (405) 271-3548
University of Oklahoma Health Sciences Center
Department of Cell Biology
P.O. Box 26901
Oklahoma City, OK 73126-0901
Abstract of Ongoing Research:
The circuitry of the central nervous system is characterized by exquisitely precise patterns of synaptic connections between nerve cells. Disruptions in these connections and their function are associated with a wide range of neural diseases. Research in my lab focuses on the organization of synapses in health and disease. A major focus is a multi-lab collaboration exploring the synaptic functions of the enzyme ELOVL4 (Elongation of Very Long Chain Fatty Acids-4) and its Very Long Chain-Fatty Acid products (VLC-FA, fatty acids with ≥ 28 carbons). Three different sets of mutations in ELOVL4 cause three distinct neurodegenerative diseases, Spinocerebellar Ataxia-34 (SCA34), Stargardt-like macular dystrophy (STDG3) or a devastating syndrome characterized by seizures, intellectual disability, spastic quadriplegia, and ichthyosis (a skin disorder). Our recent findings indicate that VLC-Saturated Fatty Acids are important regulators of synaptic function. This project examines the molecular mechanisms and downstream effects of ELOVL4 mutations and VLC-Saturated Fatty Acid deficiency on synaptic structure, organization and function in the brain and retina at the molecular, biochemical, physiological, and neuroanatomical levels. A second area of interest in the lab is understanding how the exquisite specificity of synaptic connections in the central nervous system are incompletely understood. This project investigates the roles of various families of synaptic adhesion molecules in determining the organization and selectivity of the complex synaptic interactions at the terminals of rod and cone photoreceptors in the retina. Understanding the mechanisms that shape synaptic connections and function is critical to developing new approaches to alleviate synaptic transmission deficits associated with disease (SCA, epilepsy, retinal degeneration, etc.) or to promote repair of circuits damaged by injury or degenerative disease.
Nagaraja RY*, Sherry DM*, Fessler JL, Stiles MA, Li F, Multani K, Ahmad M, Brush RS, Anderson RE, Agbaga MP, Deák F. 2021. W246G mutant ELOVL4 impairs synaptic plasticity in parallel and climbing fibers and causes motor defects in a rat model of SCA34. Molecular Neurobiology. doi: 10.1007/s12035-021-02439-1 (*co-1st authors) PMID: 34227061.
Agbaga MP, Stiles MA, Brush RS, Sullivan MT, Machalinski A, Jones KL, Anderson RE, Sherry DM. 2020. The Elovl4 spinocerebellar ataxia-34 mutation 736T>G (p.W246G) impairs retinal function in the absence of photoreceptor degeneration. Mol Neurobiol. doi: 10.1007/s12035-020-02052-8. PMID: 32780351
Deák F, Anderson RE, Fessler JL, Sherry DM. Novel cellular functions of very long chain-fatty acids: Insights from ELOVL4 mutations. Front Cell Neurosci. 2019 Sep 20;13:428. doi: 10.3389/fncel.2019.00428. eCollection 2019. PMID: 31616255
Hopiavuori BR, Deák F, Wilkerson JL, Brush RS, Rocha-Hopiavuori NA, Hopiavuori AR, Ozan KG, Sullivan MT, Wren JD, Georgescu C, Szweda L, Awasthi V, Towner R, Sherry DM, Anderson RE, Agbaga M-P. 2018. Homozygous expression of mutant ELOVL4 leads to seizures and death in a novel animal model of very long-chain fatty acid deficiency. Mol. Neurobiol. 55:1795-1813. DOI: 10.1007/s12035-017-0824-8 PMC5820379
Sherry DM, Hopiavuori BR, Stiles MA, Rahman NS, Ozan KG, Deák F, Agbaga M-P, Anderson, RE. 2017. Distribution of ELOVL4 in the developing and adult mouse brain. Front Neurosci. Front Neuroanat. 1:38. doi: 10.3389/fnana.2017.00038. PMC5410580.
Kakahel M, Tebbe L, Makia MS, Conley SM, Sherry DM, Al-Ubaidi MR, Naash MI. 2020. Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and survival. Proc Natl Acad Sci USA 117:20615-20624. PMCID: PMC6763723
Sherry DM, Kanan Y, Hamilton R, Hoffhines A, Arbogast KL, Fliesler SJ, Naash MI, Moore KL, Al-Ubaidi MR. 2012. Differential developmental deficits in retinal function in the absence of either protein tyrosine sulfotransferase-1 or -2. PLoS One. 7:e39702. PMC3382163.
Sherry DM, Blackburn BA. 2013. P-Rex2, a Rac-guanine nucleotide exchange factor, is expressed selectively in ribbon synaptic terminals of the mouse retina. BMC Neurosci. 14:70. PMCID: PMC3716592
Complete list of publications:
Profile Last Updated: November 22, 2021