Background & Research Interests:
Dan earned a B.S. in Behavioral Neuroscience from Northeastern University in 2012, graduating summa cum laude from the College of Science Honor’s Program. Prior to beginning his graduate work in the Biomolecular Pharmacology Ph.D. program at Boston University, Dan worked as a research assistant at Biogen Idec where he studied mechanisms of axonal regeneration and remyelination in animal and cell culture models of Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Dan’s long term research interests focus on the discovery and development of disease modifying therapies for the treatment of neurodegenerative disorders.
Thesis Research at BU:
RNA binding proteins have diverse regulatory roles in the transcription, splicing, transport, translation, and stability of mRNA transcripts. Notably, RNA binding proteins are particularly crucial in neuronal cells which require extensive transport of mRNAs to synapses in order to facilitate the local regulation of activity-dependent protein synthesis required for the synaptic plasticity that underlies learning and memory. RNA binding proteins also mediate the reversible aggregation of stress granules, which are cytoplasmic inclusions of mRNA and protein that form transiently in response to stress-induced inhibition of global protein synthesis. Our lab has discovered that stress granules colocalize with the intraneuronal pathological tau inclusions that are characteristic of Alzheimer’s disease (AD), suggesting that tau aggregation in AD and related tauopathies might be regulated by the same processes controlling the reversible aggregation of stress granules. In AD tissue, tau directly associates with the RNA binding proteins that nucleate stress granule assembly, while stimulation of stress granule formation promotes tau pathology and neurotoxicity in primary cultured neurons. These findings identify a novel aspect of disease pathophysiology and suggest a mechanism whereby the excessive recruitment of RNA binding proteins to stress granules in disease would inhibit the normal function of RNA binding proteins in mediating mRNA splicing, transport, and translation at the synapse leading to neurodegeneration. Current aims of the project include: 1) identification of the proteins associated with pathological tau stress granules; 2) to determine how mRNA splicing and transport are modulated by chronic stress granule formation in the presence and absence of tau; 3) to determine whether inhibition of stress granule formation ameliorates disease progression in P301L tau transgenic AD mice; and 4) to elucidate the cellular stress pathways responsible for inducing pathological tau stress granules and the role of tau phosphorylation in regulating this process.
Boston University School of Medicine, Graduate Medical Sciences
Program in Biomedical Neuroscience
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Showing 10 of 13 results.
Apicco DJ, Shlevkov E, Nezich CL, Tran DT, Guilmette E, Nicholatos JW, Bantle CM, Chen Y, Glajch KE, Abraham NA, Dang LT, Kaynor GC, Tsai EA, Nguyen KH, Groot J, Liu Y, Weihofen A, Hurt JA, Runz H, Hirst WD. The Parkinson's disease-associated gene ITPKB protects against a-synuclein aggregation by regulating ER-to-mitochondria calcium release. Proc Natl Acad Sci U S A. 2021 01 05; 118(1). PMID: 33443159; PMCID: PMC7817155; DOI: 10.1073/pnas.2006476118;
Pourhaghighi R, Ash PEA, Phanse S, Goebels F, Hu LZM, Chen S, Zhang Y, Wierbowski SD, Boudeau S, Moutaoufik MT, Malty RH, Malolepsza E, Tsafou K, Nathan A, Cromar G, Guo H, Al Abdullatif A, Apicco DJ, Becker LA, Gitler AD, Pulst SM, Youssef A, Hekman R, Havugimana PC, White CA, Blum BC, Ratti A, Bryant CD, Parkinson J, Lage K, Babu M, Yu H, Bader GD, Wolozin B, Emili A. BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain. Cell Syst. 2020 Aug 26; 11(2):208.View Related Profiles. PMID: 32853540
Pourhaghighi R, Ash PEA, Phanse S, Goebels F, Hu LZM, Chen S, Zhang Y, Wierbowski SD, Boudeau S, Moutaoufik MT, Malty RH, Malolepsza E, Tsafou K, Nathan A, Cromar G, Guo H, Abdullatif AA, Apicco DJ, Becker LA, Gitler AD, Pulst SM, Youssef A, Hekman R, Havugimana PC, White CA, Blum BC, Ratti A, Bryant CD, Parkinson J, Lage K, Babu M, Yu H, Bader GD, Wolozin B, Emili A. BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain. Cell Syst. 2020 04 22; 10(4):333-350.e14.View Related Profiles. PMID: 32325033; PMCID: PMC7938770; DOI: 10.1016/j.cels.2020.03.003;
Ruan QT, Yazdani N, Blum BC, Beierle JA, Lin W, Coelho MA, Fultz EK, Healy AF, Shahin JR, Kandola AK, Luttik KP, Zheng K, Smith NJ, Cheung J, Mortazavi F, Apicco DJ, Ragu Varman D, Ramamoorthy S, Ash PEA, Rosene DL, Emili A, Wolozin B, Szumlinski KK, Bryant CD. A Mutation in Hnrnph1 That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins. J Neurosci. 2020 01 02; 40(1):107-130.View Related Profiles. PMID: 31704785; PMCID: PMC6939476; DOI: 10.1523/JNEUROSCI.1808-19.2019;
Maziuk BF, Apicco DJ, Cruz AL, Jiang L, Ash PEA, da Rocha EL, Zhang C, Yu WH, Leszyk J, Abisambra JF, Li H, Wolozin B. RNA binding proteins co-localize with small tau inclusions in tauopathy. Acta Neuropathol Commun. 2018 08 01; 6(1):71.View Related Profiles. PMID: 30068389; PMCID: PMC6069705; DOI: 10.1186/s40478-018-0574-5;
Ruan QT, Yazdani N, Beierle JA, Hixson KM, Hokenson KE, Apicco DJ, Luttik KP, Zheng K, Maziuk BF, Ash PEA, Szumlinski KK, Russek SJ, Wolozin B, Bryant CD. Changes in neuronal immunofluorescence in the C- versus N-terminal domains of hnRNP H following D1 dopamine receptor activation. Neurosci Lett. 2018 09 25; 684:109-114.View Related Profiles. PMID: 30003938; PMCID: PMC6330092; DOI: 10.1016/j.neulet.2018.07.015;
Apicco DJ, Ash PEA, Maziuk B, LeBlang C, Medalla M, Al Abdullatif A, Ferragud A, Botelho E, Ballance HI, Dhawan U, Boudeau S, Cruz AL, Kashy D, Wong A, Goldberg LR, Yazdani N, Zhang C, Ung CY, Tripodis Y, Kanaan NM, Ikezu T, Cottone P, Leszyk J, Li H, Luebke J, Bryant CD, Wolozin B. Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. Nat Neurosci. 2018 01; 21(1):72-80.View Related Profiles. PMID: 29273772; PMCID: PMC5745051; DOI: 10.1038/s41593-017-0022-z;
Vanderweyde T, Apicco DJ, Youmans-Kidder K, Ash PEA, Cook C, Lummertz da Rocha E, Jansen-West K, Frame AA, Citro A, Leszyk JD, Ivanov P, Abisambra JF, Steffen M, Li H, Petrucelli L, Wolozin B. Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity. Cell Rep. 2016 May 17; 15(7):1455-1466.View Related Profiles. PMID: 27160897; PMCID: PMC5325702; DOI: 10.1016/j.celrep.2016.04.045;
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