Molecular Virology: Virology laboratories
The Spiegel Laboratory works in the area of “Synthetic Immunology,” which integrates synthetic chemistry, immunology, and cell biology toward the development of systems capable of controlling and/or creating human immunity. In particular, the lab has developed a class of antibody-recruiting small molecules (ARMs) that are capable of enhancing recognition of diverse pathogens by the human immune system. We have successfully employed this approach in targeting both HIV and prostate cancer, and are currently expanding its scope toward other diseases as well. Other areas of interest include re-engineering bacteria to perform complex immunological tasks, and investigations into advanced glycation end-products (AGEs), a poorly understood class of immunomodulatory post-translational modifications of proteins.
Synthetic Immunology to Engineer Human Immunity
Spiegel DA. Synthetic Immunology to Engineer Human Immunity. Nature Chemical Biology. 2010; 6; 871-872. Chosen as one of eight recipients of the 2010 Grand Challenges in Chemical Biology Competition.
A Biosynthetic Strategy for Re-engineering the S. aureus Cell Wall with Non-Native Small Molecules
Nelson JW, Chamessian AG, McEnaney PJ, Kazmierczak BI, Spiegel DA. A Biosynthetic Strategy for Re-engineering the S. aureus Cell Wall with Non-Native Small Molecules. ACS Chemical Biology. 2010, 1147-1155.
Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules
Zhang AX, Murelli RP, Barinka C, Michel J, Cocleaza A,** Jorgensen WL, Lubkowski J, Spiegel DA. A Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules. Journal of the American Chemical Society. 2010, 12711-12716.
Chemical control over immune recognition: A class of antibody-recruiting small molecules that target prostate cancer.
Murelli RM, Zhang AX, Michel J, Jorgensen WL, Spiegel DA. Chemical control over immune recognition: A class of antibody-recruiting small molecules that target prostate cancer. Journal of the American Chemical Society. 2009; 131; 17090-17092.
An antibody-recruiting small molecule that targets HIV gp120
Parker CG, Domaoal RA, Anderson KS, Spiegel DA. An antibody-recruiting small molecule that targets HIV gp120. Journal of the American Chemical Society. 2009;131: 16392-16394. This work was featured as a news story in ACS Chemical Biology, 2009, 4, 975.
Full List of PubMed Publications
- Vastl J, Wang T, Trinh TB, Spiegel DA: Encoded Silicon-Chip-Based Platform for Combinatorial Synthesis and Screening. ACS Comb Sci. 2017 Apr 10; 2017 Mar 6. PMID: 28263558
- Yehuda R, Spiegel D, Southwick S, Davis LL, Neylan TC, Krystal JH: What I have changed my mind about and why. Eur J Psychotraumatol. 2016; 2016 Nov 8. PMID: 27837585
- O'Neill KM, Greenberg SL, Cherian M, Gillies RD, Daniels KM, Roy N, Raykar NP, Riesel JN, Spiegel D, Watters DA, Gruen RL: Bellwether Procedures for Monitoring and Planning Essential Surgical Care in Low- and Middle-Income Countries: Caesarean Delivery, Laparotomy, and Treatment of Open Fractures. World J Surg. 2016 Nov. PMID: 27351714
- Nokin MJ, Durieux F, Peixoto P, Chiavarina B, Peulen O, Blomme A, Turtoi A, Costanza B, Smargiasso N, Baiwir D, Scheijen JL, Schalkwijk CG, Leenders J, De Tullio P, Bianchi E, Thiry M, Uchida K, Spiegel DA, Cochrane JR, Hutton CA, De Pauw E, Delvenne P, Belpomme D, Castronovo V, Bellahcène A: Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis. Elife. 2016 Oct 19; 2016 Oct 19. PMID: 27759563
- Rebholz WN, Cash E, Zimmaro LA, Bayley-Veloso R, Phillips K, Siwik C, Chagpar AB, Dhabhar FS, Spiegel D, Bell BS, Sephton SE: Distress and quality of life in an ethnically diverse sample awaiting breast cancer surgery. J Health Psychol. 2016 Jul 26; 2016 Jul 26. PMID: 27466289
- Rullo AF, Fitzgerald KJ, Muthusamy V, Liu M, Yuan C, Huang M, Kim M, Cho AE, Spiegel DA: Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor. Angew Chem Int Ed Engl. 2016 Mar 7; 2016 Feb 16. PMID: 26879524
- Gautam S, Kim T, Lester E, Deep D, Spiegel DA: Wall teichoic acids prevent antibody binding to epitopes within the cell wall of Staphylococcus aureus. ACS Chem Biol. 2016 Jan 15; 2015 Nov 5. PMID: 26502318
- Gray MA, Tao RN, DePorter SM, Spiegel DA, McNaughton BR: A Nanobody Activation Immunotherapeutic that Selectively Destroys HER2-Positive Breast Cancer Cells. Chembiochem. 2016 Jan; 2015 Dec 10. PMID: 26556305
- Wang T, Streeter MD, Spiegel DA: Generation and characterization of antibodies against arginine-derived advanced glycation endproducts. Bioorg Med Chem Lett. 2015 Nov 1; 2015 Jun 11. PMID: 26117561
- Draghici C, Wang T, Spiegel DA: Concise total synthesis of glucosepane. Science. 2015 Oct 16. PMID: 26472902
- Gautam S, Kim T, Shoda T, Sen S, Deep D, Luthra R, Ferreira MT, Pinho MG, Spiegel DA: An Activity-Based Probe for Studying Crosslinking in Live Bacteria. Angew Chem Int Ed Engl. 2015 Sep 1; 2015 Jul 17. PMID: 26204841
- Gautam S, Kim T, Spiegel DA: Chemical probes reveal an extraseptal mode of cross-linking in Staphylococcus aureus. J Am Chem Soc. 2015 Jun 17; 2015 Jun 2. PMID: 26035224
- Dimitrievska S, Cai C, Weyers A, Balestrini JL, Lin T, Sundaram S, Hatachi G, Spiegel DA, Kyriakides TR, Miao J, Li G, Niklason LE, Linhardt RJ: Click-coated, heparinized, decellularized vascular grafts. Acta Biomater. 2015 Feb; 2014 Nov 20. PMID: 25463496
- McEnaney PJ, Fitzgerald KJ, Zhang AX, Douglass EF Jr, Shan W, Balog A, Kolesnikova MD, Spiegel DA: Chemically synthesized molecules with the targeting and effector functions of antibodies. J Am Chem Soc. 2014 Dec 31; 2014 Dec 16. PMID: 25514603
- Parker CG, Dahlgren MK, Tao RN, Li DT, Douglass EF Jr, Shoda T, Jawanda N, Spasov KA, Lee S, Zhou N, Domaoal RA, Sutton RE, Anderson KS, Jorgensen WL, Krystal M, Spiegel DA: Illuminating HIV gp120-Ligand Recognition through Computationally-Driven Optimization of Antibody-Recruiting Molecules. Chem Sci. 2014 Jun 1. PMID: 25379167
- Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI: Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metab. 2013 Nov 5. PMID: 24206666
- Wang T, Douglass EF Jr, Fitzgerald KJ, Spiegel DA: A "turn-on" fluorescent sensor for methylglyoxal. J Am Chem Soc. 2013 Aug 21; 2013 Aug 9. PMID: 23931147
- Douglass EF Jr, Miller CJ, Sparer G, Shapiro H, Spiegel DA: A comprehensive mathematical model for three-body binding equilibria. J Am Chem Soc. 2013 Apr 24; 2013 Apr 16. PMID: 23544844
- Gautam S, Gniadek TJ, Kim T, Spiegel DA: Exterior design: strategies for redecorating the bacterial surface with small molecules. Trends Biotechnol. 2013 Apr; 2013 Mar 13. PMID: 23490213
- Kim T, Spiegel DA: The unique reactivity of N-phenacyl-derived thiazolium salts toward α-dicarbonyl compounds. Rejuvenation Res. 2013 Feb. PMID: 23186164
- McEnaney PJ, Parker CG, Zhang AX, Spiegel DA: Antibody-recruiting molecules: an emerging paradigm for engaging immune function in treating human disease. ACS Chem Biol. 2012 Jul 20; 2012 Jul 3. PMID: 22758917
- Wang T, Kartika R, Spiegel DA: Exploring post-translational arginine modification using chemically synthesized methylglyoxal hydroimidazolones. J Am Chem Soc. 2012 May 30; 2012 May 16. PMID: 22591136
- Jakobsche CE, McEnaney PJ, Zhang AX, Spiegel DA: Reprogramming urokinase into an antibody-recruiting anticancer agent. ACS Chem Biol. 2012 Feb 17; 2011 Nov 18. PMID: 22098560
- Nelson JW, Chamessian AG, McEnaney PJ, Murelli RP, Kazmierczak BI, Spiegel DA: A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules. ACS Chem Biol. 2010 Dec 17; 2010 Oct 5. PMID: 20923200
- Spiegel DA: Grand challenge commentary: Synthetic immunology to engineer human immunity. Nat Chem Biol. 2010 Dec. PMID: 21079593
- Zhang AX, Murelli RP, Barinka C, Michel J, Cocleaza A, Jorgensen WL, Lubkowski J, Spiegel DA: A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules. J Am Chem Soc. 2010 Sep 15. PMID: 20726553
- Murelli RP, Zhang AX, Michel J, Jorgensen WL, Spiegel DA: Chemical control over immune recognition: a class of antibody-recruiting small molecules that target prostate cancer. J Am Chem Soc. 2009 Dec 2. PMID: 19888723
- Parker CG, Domaoal RA, Anderson KS, Spiegel DA: An antibody-recruiting small molecule that targets HIV gp120. J Am Chem Soc. 2009 Nov 18. PMID: 19839582
- Spiegel DA, Wiberg KB, Schacherer LN, Medeiros MR, Wood JL: Deoxygenation of alcohols employing water as the hydrogen atom source. J Am Chem Soc. 2005 Sep 14. PMID: 16144398
- Spiegel DA, Njardarson JT, McDonald IM, Wood JL: The art of innovation in organic chemistry: synthetic efforts toward the phomoidrides. Chem Rev. 2003 Jul. PMID: 12848583