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Greg A. Snyder
 

Greg A. Snyder Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Medicine
Secondary Appointments: Microbiology and Immunology
gsnyder@som.umaryland.edu
Location: IHV, Office: N357, Lab: N356
Phone: 410-706-7977
Fax: 410-706-6695
Lab: 410-706-7457
 

Personal History:

I joined the Institute of Human Virology as a Faculty Research Associate within the Sundberg Research Group where I helped to establish X-ray data collection and structure determination capacities both in house and remotely at national synchrotron laboratories. In July of 2013, I became an Assistant Professor as part of an UMB-IHV faculty development initiative to establish my independent research laboratory investigating host-pathogen interactions and immune modulation. During this time I have continued with my previous research investigating Toll-like and Interleukin-1 Receptor signaling.

I received a B.S. in chemistry from Creighton University, Omaha, NE and a Ph.D. from Northwestern University, Evanston, Il. My thesis research focused on the structural characterization and binding of the C-type lectin receptor DC-SIGN/CD209/L with the HIV-1 glyco-envelope protein, gp120. These studies led to structure determination of DC-SIGN and a prediction algorithm for glycoprotein footprints recognized by C-type lectins.

I performed postdoctoral research in the Laboratory of Immunology – Structural Immunobiology Unit, NIAID, NIH Bethesda, MD. These studies focused on understanding Toll-Like and Interleukin-1 Receptor (TIR) resistance signaling and resulted in the structure determination of TIR signaling molecules, MyD88, TIRAP/Mal and more recently a the NIAID category B priority pathogen Brucella melitensis bacterial TIR protein (TcpB). These structural studies led to molecular and functional characterization of novel microbial derived inhibitory peptides which selectively inhibit TLR-4 and MyD88 signaling pathways.

Research Interests:

Innate Immune Response and Inflammation.

General Questions:

How do organisms evaluate self from non-self, pathogenic from benign and environmental stimuli from potential food source?

What are the molecular determinants of immune response and inflammation?

Within this framework the laboratory focuses on characterizing the molecular processes underlying immune function, dysfunction and inflammation.  To this end we are currently pursuing studies of host-microbe recognition systems involving inflammation, immune modulation and dysfunction.

Pattern recognition by Toll-like and Interleukin-1 receptor signaling pathways.

Appropriate immune responses to exogenous and endogenous stimuli  mount measured and homeostatic responses, while uncontrolled responses, chronic or acute can lead to inflammatory disease and death. The Toll-like receptors (TLRs) constitute a family of pattern recognition receptors of the innate immune system, which are activated in response to microbial-, danger- and self- associated molecular patterns (MAMPs, DAMPs and SAMPs) found on a variety of fungal, bacterial, viral, endogenous and environmental stimuli. Receptor activation triggers a signal transduction cascade involving cytoplasmic domains shared by Toll-like and Interleukin-1 Receptors (TIR) that result in NF-¿B-mediated induction of cytokine- and chemokine-driven inflammatory responses. Dysregulation of innate immune signaling pathways have been implicated in numerous human diseases, including cancer, autoimmunity, atherosclerosis, ischemic injury and inflammatory disease. Conversely, controlled activation of innate pathways is a promising pathway to novel and improved vaccine adjuvant design.

Microbial subversion of Toll-like and interleukin -1 Receptor Signaling.

Recently, Bacterial and Viral TIR-interacting proteins (TIPs) capable of inhibiting TLR and IL-1R signaling as a mechanism for immune evasion, have been identified, The molecular interactions in the cytoplasm that drive, endogenously regulate and exogenously subvert TLR and Interleukin-1 receptor signal transduction for modulating immune responses are poorly understood.


Publications:

  1. The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation.
    Wang X, Shaw DK, Sakhon OS, Snyder GA, Sundberg EJ, Santambrogio L, Sutterwala FS, Dumler JS, Shirey KA, Perkins DJ, Richard K, Chagas AC, Calvo E, Kopecký J, Kotsyfakis M, Pedra JH. Infect Immun. 2016 May 24;84(6):1796-805. doi: 10.1128/IAI.01526-15. Print 2016 Jun. PMID: 27045038 [PubMed - in process] Similar articles
  2. A Comparative Analysis of the Mechanism of Toll-Like Receptor-Disruption by TIR-Containing Protein C from Uropathogenic Escherichia coli.
    Waldhuber A, Snyder GA, Römmler F, Cirl C, Müller T, Xiao TS, Svanborg C, Miethke T. Pathogens. 2016 Feb 29;5(1). pii: E25. doi: 10.3390/pathogens5010025. PMID: 26938564 [PubMed] Free PMC Article Similar articles
  3. A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza.
    Piao W, Shirey KA, Ru LW, Lai W, Szmacinski H, Snyder GA, Sundberg EJ, Lakowicz JR, Vogel SN, Toshchakov VY. Cell Rep. 2015 Jun 30;11(12):1941-52. doi: 10.1016/j.celrep.2015.05.035. Epub 2015 Jun 18. PMID: 26095366 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  4. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain.
    Mistry P, Laird MH, Schwarz RS, Greene S, Dyson T, Snyder GA, Xiao TS, Chauhan J, Fletcher S, Toshchakov VY, MacKerell AD Jr, Vogel SN. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5455-60. doi: 10.1073/pnas.1422576112. Epub 2015 Apr 13. PMID: 25870276 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  5. Cardiac troponin I Pro82Ser variant induces diastolic dysfunction, blunts ß-adrenergic response, and impairs myofilament cooperativity.
    Ramirez-Correa GA, Frazier AH, Zhu G, Zhang P, Rappold T, Kooij V, Bedja D, Snyder GA, Lugo-Fagundo NS, Hariharan R, Li Y, Shen X, Gao WD, Cingolani OH, Takimoto E, Foster DB, Murphy AM. J Appl Physiol (1985). 2015 Jan 15;118(2):212-23. doi: 10.1152/japplphysiol.00463.2014. Epub 2014 Oct 16. PMID: 25324519 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  6. Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies.
    Trastoy B, Lomino JV, Pierce BG, Carter LG, Günther S, Giddens JP, Snyder GA, Weiss TM, Weng Z, Wang LX, Sundberg EJ. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6714-9. doi: 10.1073/pnas.1322908111. Epub 2014 Apr 21. PMID: 24753590 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  7. The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation during Anaplasma phagocytophilum infection.
    Chen G, Wang X, Severo MS, Sakhon OS, Sohail M, Brown LJ, Sircar M, Snyder GA, Sundberg EJ, Ulland TK, Olivier AK, Andersen JF, Zhou Y, Shi GP, Sutterwala FS, Kotsyfakis M, Pedra JH. Infect Immun. 2014 Jun;82(6):2553-64. doi: 10.1128/IAI.01679-14. Epub 2014 Mar 31. PMID: 24686067 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  8. Structure of Clostridium difficile PilJ exhibits unprecedented divergence from known type IV pilins.
    Piepenbrink KH, Maldarelli GA, de la Peña CF, Mulvey GL, Snyder GA, De Masi L, von Rosenvinge EC, Günther S, Armstrong GD, Donnenberg MS, Sundberg EJ. J Biol Chem. 2014 Feb 14;289(7):4334-45. doi: 10.1074/jbc.M113.534404. Epub 2013 Dec 21. PMID: 24362261 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  9. Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.
    Snyder GA, Deredge D, Waldhuber A, Fresquez T, Wilkins DZ, Smith PT, Durr S, Cirl C, Jiang J, Jennings W, Luchetti T, Snyder N, Sundberg EJ, Wintrode P, Miethke T, Xiao TS. J Biol Chem. 2014 Jan 10;289(2):669-79. doi: 10.1074/jbc.M113.523407. Epub 2013 Nov 25. PMID: 24275656 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  10. Molecular interactions in interleukin and toll-like receptor signaling pathways.
    Snyder GA, Sundberg EJ. Curr Pharm Des. 2014;20(8):1244-58. Review. PMID: 23713776 [PubMed - indexed for MEDLINE] Similar articles
  11. Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.
    Snyder GA, Cirl C, Jiang J, Chen K, Waldhuber A, Smith P, Römmler F, Snyder N, Fresquez T, Dürr S, Tjandra N, Miethke T, Xiao TS. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6985-90. doi: 10.1073/pnas.1215770110. Epub 2013 Apr 8. PMID: 23569230 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  12. R753Q polymorphism inhibits Toll-like receptor (TLR) 2 tyrosine phosphorylation, dimerization with TLR6, and recruitment of myeloid differentiation primary response protein 88.
    Xiong Y, Song C, Snyder GA, Sundberg EJ, Medvedev AE. J Biol Chem. 2012 Nov 2;287(45):38327-37. doi: 10.1074/jbc.M112.375493. Epub 2012 Sep 19. PMID: 22992740 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  13. Characterization of DC-SIGN/R interaction with human immunodeficiency virus type 1 gp120 and ICAM molecules favors the receptor's role as an antigen-capturing rather than an adhesion receptor.
    Snyder GA, Ford J, Torabi-Parizi P, Arthos JA, Schuck P, Colonna M, Sun PD. J Virol. 2005 Apr;79(8):4589-98. PMID: 15795245 [PubMed - indexed for MEDLINE] Free PMC Article Similar articles
  14. The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer.
    Snyder GA, Colonna M, Sun PD. J Mol Biol. 2005 Apr 15;347(5):979-89. PMID: 15784257 [PubMed - indexed for MEDLINE] Similar articles