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Sean P Ryder PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentBiochemistry and Molecular Pharmacology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Phone508-856-1372
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionUMMS - School of Medicine
    DepartmentRNA Therapeutics Institute

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBioinformatics and Computational Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentNeuroscience

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentTranslational Science

    InstitutionUMMS - Programs, Centers and Institutes
    DepartmentBioinformatics and Integrative Biology


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    Collapse Biography 
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    University of New Hampshire Manchester, Durham, NH, United StatesB SBiochemistry
    Yale University, New Haven, CT, United StatesPH DMolecular Biophysics & Biochem

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    Please see the Ryder lab website.



    Academic Background



    Sean Ryder graduated from the University of New Hampshire in 1995 with a bachelor’s degree in biochemistry. He studied the mechanisms of RNA folding and catalysis in the Department of Molecular Biophysics and Biochemistry at Yale University, earning a Ph.D. in 2001. He performed post-doctoral research at The Scripps Research Institute, where he was awarded a Damon Runyon fellowship to study post-transcriptional regulation and RNP assembly. He joined the faculty of the University of Massachusetts Medical School in 2005. His current research focuses on the role of RNA-binding proteins in the regulation of gene expression during differentiation and development, with a focus on oligodendrocyte biology and early embryogenesis. His work couples quantitative methods, molecular genetics, and high throughput approaches to map regulatory networks. He received a Scholar Award from the Worcester Foundation for Biomedical Research in 2006, and a Basil O’Connor Award from the March of Dimes in 2008.





    Post-transcriptional regulation of maternal mRNA in development.



    A major theme that emerges from the study of embryogenesis is that post-transcriptional regulation of maternal mRNAs is crucial to patterning of the developing zygote. As oocytes ripen, the chromosomal content of the egg is locked in meiosis until the time of fertilization, precluding transcription of the mRNAs inherited by the new organism. Maternal transcripts are produced and reversibly silenced in the earlier stages of oogenesis, in some organisms requiring the support of “nurse” cells to provide mRNA to the maturing oocyte. Moreover, the embryos of most animals do not transcribe their DNA until the zygote has divided one or more times. In most cases, zygotic transcription does not begin until several cell divisions have occurred, after a number of patterning and cell fate specification events have taken place. Thus, activation of maternal transcripts by maternal regulatory factors provides the starting point for formation of the body plan.



    We are mapping the post-transcriptional regulatory circuitry that guides axis formation and cell fate specification in the nematode Caenorhabditis elegans. We use a combination of biochemical, biophysical, and molecular genetic methods to define the nucleotide sequence specificity and RNA-target specificity of each RNA-binding protein required for patterning. Through this work, will generate a comprehensive list of cis-acting regulatory sites in maternal transcripts. This work will provide a map that will guide dissection of the post-transcriptional regulatory mechanisms that contribute to development.







    Post-transcriptional regulation of myelin formation.



    Myelin is required for function of the vertebrate nervous system. It has a stereotypical structure, consisting of spiraling layers of specialized plasma membrane, containing a defined set of phospholipids and proteins. Many of these proteins are vital for myelin formation or maintenance. While it has long been known that myelin enhances the propagation of saltatory electrical impulses along the length of the myelinated axon, more recent studies have revealed additional functions. Mice with mutations in myelin proteins suffer from axon degeneration, demonstrating that myelin is required to maintain axon integrity. Additionally, interactions between myelin proteins and developing axons inhibit neurite outgrowth and suppress developmental plasticity. Thus, myelin is required for proper connectivity during neural development and for electrical activity and maintenance of mature neurons.



    In the central nervous system, myelin is formed by specialized glial cells termed oligodendrocytes. The highly polarized nature of oligodendrocytes, together with the requirement that they sense and respond accurately to their extracellular environment, necessitates the development of strategies to control gene expression at regions distal to the cell body. These strategies could influence how the cell decides where to migrate, when to stop dividing and differentiate, and which axons to myelinate. Changes in gene expression at the post-transcriptional or post-translational level allow the cell to respond rapidly and regionally, compared to transcriptional changes that require involvement of the nucleus. Accordingly, several RNA-binding proteins are expressed in cells of the oligodendrocyte lineage where they play regulatory roles in oligodendrocyte maturation or myelin formation. We are mapping the RNA regulatory circuitry that guides oligodendrocyte differentiation.





    Screening for small molecule inhibitors of nematode development. 



    Early developmental phenomena are guided by the asymmetric regulation of maternally supplied proteins and transcripts. Protein expression from maternal mRNAs is governed by a suite of RNA-binding proteins packaged into the cytoplasm during oogenesis. These RNA-binding proteins control the stability, translation efficiency, and/or localization pattern of distinct transcripts by recognizing sequence elements in the 3’-untranslated region (UTR) of target mRNAs. Currently, few tools exist to study specific regulatory networks guided by RNA-binding proteins during early development. Importantly, standard genetic analyses are complicated by the maternal effect, pleiotropy, and embryonic lethality. In order to dissect the spatial and temporal aspects of post-transcriptional regulation as a function of developmental stage, a set of small molecules that modulate the RNA-binding activity of these maternal factors is needed. Towards this end, we have established fluorescence polarization (FP) assays to monitor the association of several nematode proteins with RNA in vitro. We are screening for small molecule inhibitors using both our on-site small molecule screening facility and in collaboration with the MLPCN of the NIH. If specific inhibitors of nematode embryogenesis can be identified, these could potentially form a new class of anti-helminthics useful in the treatment of parasitic nematode infections.





     



    Collapse Rotation Projects

    Potential Rotation Projects

    A variety of rotation projects are available to study RNP assembly and post-transcriptional regulation during development using quantitative biochemical and modern molecular methods.

    Project 1: Characterization of the RNA-protein complexes that guide C. elegans early development. Several projects ranging in scope from biochemical characterization of RNA-binding protein complexes to genetic dissection of RNA binding protein function in development are currently available. Contact Sean for more details.

    Project 2: Post-transcriptional regulation of oligodendrocyte differentiation. Projects are available to monitor changes in gene expression as a function of differentiation with a focus on changes in alternative splicing and mRNA stability. Contact Sean for more details.




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Thokala P, Simpson EL, Tappenden P, Stevens JW, Dickinson K, Ryder S, Harrison P. Ledipasvir-Sofosbuvir for Treating Chronic Hepatitis C: A NICE Single Technology Appraisal-An Evidence Review Group Perspective. Pharmacoeconomics. 2016 Aug; 34(8):741-50. PMID: 26892974.
      View in: PubMed
    2. Kaymak E, Farley BM, Hay SA, Li C, Ho S, Hartman DJ, Ryder SP. Efficient generation of transgenic reporter strains and analysis of expression patterns in Caenorhabditis elegans using library MosSCI. Dev Dyn. 2016 Sep; 245(9):925-36. PMID: 27294288.
      View in: PubMed
    3. Elewa A, Shirayama M, Kaymak E, Harrison PF, Powell DR, Du Z, Chute CD, Woolf H, Yi D, Ishidate T, Srinivasan J, Bao Z, Beilharz TH, Ryder SP, Mello CC. POS-1 Promotes Endo-mesoderm Development by Inhibiting the Cytoplasmic Polyadenylation of neg-1 mRNA. Dev Cell. 2015 Jul 6; 34(1):108-18. PMID: 26096734.
      View in: PubMed
    4. Bohn MF, Shandilya SM, Silvas TV, Nalivaika EA, Kouno T, Kelch BA, Ryder SP, Kurt-Yilmaz N, Somasundaran M, Schiffer CA. The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization. Structure. 2015 May 5; 23(5):903-11. PMID: 25914058.
      View in: PubMed
    5. Ryder SP. Personal reflection (RNA journal 20th anniversary). RNA. 2015 Apr; 21(4):725-6. PMID: 25780210.
      View in: PubMed
    6. Zearfoss NR, Deveau LM, Clingman CC, Schmidt E, Johnson ES, Massi F, Ryder SP. A conserved three-nucleotide core motif defines Musashi RNA binding specificity. J Biol Chem. 2014 Dec 19; 289(51):35530-41. PMID: 25368328.
      View in: PubMed
    7. Clingman CC, Deveau LM, Hay SA, Genga RM, Shandilya SM, Massi F, Ryder SP. Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite. Elife. 2014 Jun 16; 3. PMID: 24935936.
      View in: PubMed
    8. Kaymak E, Ryder SP. RNA recognition by the Caenorhabditis elegans oocyte maturation determinant OMA-1. J Biol Chem. 2013 Oct 18; 288(42):30463-72. PMID: 24014033.
      View in: PubMed
    9. Zearfoss NR, Johnson ES, Ryder SP. hnRNP A1 and secondary structure coordinate alternative splicing of Mag. RNA. 2013 Jul; 19(7):948-57. PMID: 23704325.
      View in: PubMed
    10. Clingman CC, Ryder SP. Metabolite sensing in eukaryotic mRNA biology. Wiley Interdiscip Rev RNA. 2013 Jul-Aug; 4(4):387-96. PMID: 23653333.
      View in: PubMed
    11. Tamburino AM, Ryder SP, Walhout AJ. A compendium of Caenorhabditis elegans RNA binding proteins predicts extensive regulation at multiple levels. G3 (Bethesda). 2013 Feb; 3(2):297-304. PMID: 23390605.
      View in: PubMed
    12. Farley BM, Ryder SP. POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster. Mol Biol Cell. 2012 Dec; 23(23):4473-83. PMID: 23034181.
      View in: PubMed
    13. Zearfoss NR, Ryder SP. End-labeling oligonucleotides with chemical tags after synthesis. Methods Mol Biol. 2012; 941:181-93. PMID: 23065562.
      View in: PubMed
    14. Broderick JA, Salomon WE, Ryder SP, Aronin N, Zamore PD. Argonaute protein identity and pairing geometry determine cooperativity in mammalian RNA silencing. RNA. 2011 Oct; 17(10):1858-69. PMID: 21878547.
      View in: PubMed
    15. Kalchhauser I, Farley BM, Pauli S, Ryder SP, Ciosk R. FBF represses the Cip/Kip cell-cycle inhibitor CKI-2 to promote self-renewal of germline stem cells in C. elegans. EMBO J. 2011 Aug 05; 30(18):3823-9. PMID: 21822213.
      View in: PubMed
    16. Ryder SP. Pumilio RNA recognition: the consequence of promiscuity. Structure. 2011 Mar 9; 19(3):277-9. PMID: 21397178.
      View in: PubMed
    17. Zearfoss NR, Clingman CC, Farley BM, McCoig LM, Ryder SP. Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. PLoS Genet. 2011 Jan 06; 7(1):e1001269. PMID: 21253564.
      View in: PubMed
    18. Wright JE, Gaidatzis D, Senften M, Farley BM, Westhof E, Ryder SP, Ciosk R. A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1. EMBO J. 2011 Feb 2; 30(3):533-45. PMID: 21169991.
      View in: PubMed
    19. Pagano JM, Clingman CC, Ryder SP. Quantitative approaches to monitor protein-nucleic acid interactions using fluorescent probes. RNA. 2011 Jan; 17(1):14-20. PMID: 21098142.
      View in: PubMed
    20. Ryder SP. Hidden ribozymes in eukaryotic genome sequence. F1000 Biol Rep. 2010 Jul 14; 2. PMID: 20948783.
      View in: PubMed
    21. Swamidass SJ, Bittker JA, Bodycombe NE, Ryder SP, Clemons PA. An economic framework to prioritize confirmatory tests after a high-throughput screen. J Biomol Screen. 2010 Jul; 15(6):680-6. PMID: 20547534.
      View in: PubMed
    22. Kaymak E, Wee LM, Ryder SP. Structure and function of nematode RNA-binding proteins. Curr Opin Struct Biol. 2010 Jun; 20(3):305-12. PMID: 20418095.
      View in: PubMed
    23. Ryder SP, Massi F. Insights into the structural basis of RNA recognition by STAR domain proteins. Adv Exp Med Biol. 2010; 693:37-53. PMID: 21189684.
      View in: PubMed
    24. Pagano JM, Farley BM, Essien KI, Ryder SP. RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3. Proc Natl Acad Sci U S A. 2009 Dec 1; 106(48):20252-7. PMID: 19915141.
      View in: PubMed
    25. Furgason ML, MacDonald C, Shanks SG, Ryder SP, Bryant NJ, Munson M. The N-terminal peptide of the syntaxin Tlg2p modulates binding of its closed conformation to Vps45p. Proc Natl Acad Sci U S A. 2009 Aug 25; 106(34):14303-8. PMID: 19667197.
      View in: PubMed
    26. Farley BM, Pagano JM, Ryder SP. RNA target specificity of the embryonic cell fate determinant POS-1. RNA. 2008 Dec; 14(12):2685-97. PMID: 18952820.
      View in: PubMed
    27. Zearfoss NR, Farley BM, Ryder SP. Post-transcriptional regulation of myelin formation. Biochim Biophys Acta. 2008 Aug; 1779(8):486-94. PMID: 18590840.
      View in: PubMed
    28. Farley BM, Ryder SP. Regulation of maternal mRNAs in early development. Crit Rev Biochem Mol Biol. 2008 Mar-Apr; 43(2):135-62. PMID: 18365862.
      View in: PubMed
    29. Recht MI, Ryder SP, Williamson JR. Monitoring assembly of ribonucleoprotein complexes by isothermal titration calorimetry. Methods Mol Biol. 2008; 488:117-27. PMID: 18982287.
      View in: PubMed
    30. Ryder SP, Recht MI, Williamson JR. Quantitative analysis of protein-RNA interactions by gel mobility shift. Methods Mol Biol. 2008; 488:99-115. PMID: 18982286.
      View in: PubMed
    31. Pagano JM, Farley BM, McCoig LM, Ryder SP. Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5. J Biol Chem. 2007 Mar 23; 282(12):8883-94. PMID: 17264081.
      View in: PubMed
    32. Ryder SP. Oskar gains weight. Nat Struct Mol Biol. 2006 Apr; 13(4):297-9. PMID: 16715044.
      View in: PubMed
    33. Ryder SP, Williamson JR. Specificity of the STAR/GSG domain protein Qk1: implications for the regulation of myelination. RNA. 2004 Sep; 10(9):1449-58. PMID: 15273320.
      View in: PubMed
    34. Ryder SP, Frater LA, Abramovitz DL, Goodwin EB, Williamson JR. RNA target specificity of the STAR/GSG domain post-transcriptional regulatory protein GLD-1. Nat Struct Mol Biol. 2004 Jan; 11(1):20-8. PMID: 14718919.
      View in: PubMed
    35. Strobel SA, Jones FD, Oyelere AK, Ryder SP. Biochemical detection of adenosine and cytidine ionization within RNA by interference analysis. Nucleic Acids Res Suppl. 2003; (3):229-30. PMID: 14510464.
      View in: PubMed
    36. Ryder SP, Strobel SA. Comparative analysis of hairpin ribozyme structures and interference data. Nucleic Acids Res. 2002 Mar 15; 30(6):1287-91. PMID: 11884625.
      View in: PubMed
    37. Jones FD, Ryder SP, Strobel SA. An efficient ligation reaction promoted by a Varkud Satellite ribozyme with extended 5'- and 3'-termini. Nucleic Acids Res. 2001 Dec 15; 29(24):5115-20. PMID: 11812844.
      View in: PubMed
    38. Ryder SP, Oyelere AK, Padilla JL, Klostermeier D, Millar DP, Strobel SA. Investigation of adenosine base ionization in the hairpin ribozyme by nucleotide analog interference mapping. RNA. 2001 Oct; 7(10):1454-63. PMID: 11680850.
      View in: PubMed
    39. Strobel SA, Ryder SP. Biological catalysis. The hairpin's turn. Nature. 2001 Apr 12; 410(6830):761-3. PMID: 11298426.
      View in: PubMed
    40. Ryder SP, Ortoleva-Donnelly L, Kosek AB, Strobel SA. Chemical probing of RNA by nucleotide analog interference mapping. Methods Enzymol. 2000; 317:92-109. PMID: 10829274.
      View in: PubMed
    41. Hess JA, Buchanan FG, Ryder S, Exton JH. Altered activation of phospholipase D by lysophosphatidic acid and endothelin-1 in mouse embryo fibroblasts lacking phospholipase C-gamma1. Cell Signal. 2000 Jan; 12(1):37-45. PMID: 10676846.
      View in: PubMed
    42. Ryder SP, Strobel SA. Nucleotide analog interference mapping of the hairpin ribozyme: implications for secondary and tertiary structure formation. J Mol Biol. 1999 Aug 13; 291(2):295-311. PMID: 10438622.
      View in: PubMed
    43. Ryder SP, Strobel SA. Nucleotide analog interference mapping. Methods. 1999 May; 18(1):38-50. PMID: 10208815.
      View in: PubMed
    44. Szewczak AA, Ortoleva-Donnelly L, Ryder SP, Moncoeur E, Strobel SA. A minor groove RNA triple helix within the catalytic core of a group I intron. Nat Struct Biol. 1998 Dec; 5(12):1037-42. PMID: 9846872.
      View in: PubMed
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