Education:
PhD, Neuroscience, University of Florida, Gainsesville, Florida
BS, Cell Biology, University of Kansas, Lawrence, Kansas
Clinical/Research Interests:
Synopsis:
The Sherry lab explores the organization of synapses in health and disease, investigating 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 using fluorescent, confocal, super-resolution, and electron microscopy.
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 research 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 Neuro-Ichthyosis syndrome characterized by seizures, intellectual disability, spastic quadriplegia, ichthyosis (a skin disorder) and early death. 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.
Select Publications:
- Sherry DM, Stiles MA. 2022. Improved fluorescent signal in expansion microscopy using fluorescent Fab fragment secondary antibodies. MethodsX 9:101796. doi: 10.1016/j.mex.2022.101796. eCollection 2022. PMID: 36042811
- Baier MP, Nagaraja RY, Yarbrough HP, Owen DB, Masingale AM, Ranjit R, Stiles MA, Murphy A, Agbaga MP, Ahmad M, Sherry DM, Kinter MT, Van Remmen H, Logan S. 2022. Selective ablation of Sod2 in astrocytes induces sex-specific effects on cognitive function, d-serine availability and astrogliosis. J Neurosci 42:5992-6006. doi: 10.1523/JNEUROSCI.2543-21.2022.
- 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.
- 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
- Deák F, Anderson RE, Fessler JL, Sherry DM. Novel cellular functions of very long chain-fatty acids: Insight 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.
Complete list of publications:
https://www.ncbi.nlm.nih.gov/myncbi/david.sherry.1/bibliography/public/