The focus of our research is the biologically inspired synthesis of molecules and molecular assemblies with novel physical, chemical or biological properties. Although chemists are quite sophisticated in their ability to synthesize complex molecular architectures, our ability to rationally design and synthesize molecules with a desired molecular function is still in its infancy. Nature, on the other hand, has generated a vast array of molecules with remarkable properties — from the antibody molecule and enzymes to the photosynthetic center. Given Nature's "synthetic" prowess, we have undertaken an approach to synthesis in which the molecules, biosynthetic machinery and strategies of living organisms are combined with the principles and tools of physical organic and synthetic chemistry to create molecules with new functions difficult to generate by either approach alone. By studying the properties of the resulting molecules, new insights are gained into the molecular mechanisms of complex biological and chemical systems.

Schultz Lab: Playing with the Molecules of Life

Group Information

The group occupies laboratory space in the Stein Clinical Research Center, adjacent to the Beckman Center for Chemical Sciences. The lab currently consists of roughly 15 graduate students, postdoctoral fellows, and staff. Coworkers typically go on to careers in academics, biotech or the pharmaceutical industry (past group members are on the faculties of 85+ research universities around the world).

Representative Publications

20. Lucki, N.; Villa, G.R.; Vergani, N.; Bollong, M.J.; Beyer, B.A.; Lee, J.W.; Anglin, J.; Chin, E.; Sharma, A.; Johnson, K.; Gordon, P.; Skirboll, S.L.; Wurdak, H.; Schultz, P.G.; Mischel, P.S.; Lairson, L.L. "A Cell Type Selective Apoptosis-Inducing Small Molecule for the Treatment of Brain Cancer", Proc. Natl. Acad. Sci. (U.S.A.); 116(13):6435-6440, 2019 Mar 26. PDF

 

19. Li, J.C.; Liu, T.; Wang, Y.; Mehta, A.; Schultz, P.G. "Enhancing Protein Stability with Genetically Encoded Noncanonical Amino Acids", J. Am. Chem. Soc.; 140(47):15997-16000. 2018 Nov 28. PDF.

 

18. Janes, J.; Young, M.E.; Chen, E.; Rogers, N.; Burgstaller-Muehlbacher, S.; Hughes, L.; Love, M.; Hull, M.V.; Kuhen, K.L.; Woods, A.K.; Joseph, S.B.; Petrassi, H.M.; McNamara, C.W.; Tremblay, M.S.; Su, A.I.; Schultz, P.G.; Chatterjee, A. "ReFRAME:  A Comprehensive Drug Repurposing Library and its Application to Cryptosporidium Antibiotics", Proc. Natl. Acad. Sci. (USA); 115(42):10750-10755; 2018 Oct 16. PDF

 

17. Bollong, M.J.; Lee, G.; Coukos, J.S.; Yun, H.; Zambaldo, C.; Chang, J.W.; Chin, E.N.; Ahmad, I.; Chatterjee, A.K.; Lairson, L.L.; Schultz, P.G.; Moellering, R.E. "A Metabolite-Derived Protein Modification Integrates Glycolysis with KEAP1-NRF2 Signalling", Nature; 562(7728):600-604; 2018 October 15. PDF

 

16. Mehta, A.P.; Supekova, L.; Chen, J.; Pestonjamasp, K.; Webster, P.; Ko, Y.; Henderson, S.C.; McDermott, G.; Supek, F.; Schultz, P.G. "Engineering Yeast Endosymbionts as a First Step Towards the Evolution of Mitochondria", Proc. Natl. Acad. Sci. (USA); doi: 10.1073/pnas.1813143115; Epub 2018 Oct 29. PDF

 

15. Mehta, A.P. Wang, Y.; Reed, S.A.; Supekova, L.; Javahishvili, T.; Chaput, J.C.; Schultz, P.G. "A Bacterial Genome Containing Chimeric DNA-RNA Sequences" J. Am. Chem. Soc.; 140(36):11464-11473, 2018 August 30. PDF

 

14. Young, D.D.; Schultz, P.G. "Playing with the Molecules of Life", A.C.S. Chemical Biology; 13(4):854-870; 2018 April 20. PDF

 

13. Bollong, M.J., Pietilä, M.; Pearson, A.D.; Sarkar, T.R.; Ahmad, I.; Soundararajan, R.; Lyssiotis, C.A.; Mani, S.A.; Schultz, P.G.; Lairson, L.L. "A Vimentin Binding Small Molecule Leads to Mitotic Disruption in Mesenchymal Cancers", Proc. Natl. Acad. Sci. (U.S.A.); 114(46):E9903-E9912; 2017 Nov 14. PDF

 

12. Zambaldo, C.; Luo, X.; Mehta, A.P.; Schultz, P.G. “Recombinant Macrocyclic Lanthipeptides Incorporating Non-Canonical Amino Acids”, J. Am. Chem. Soc.; 139(34):11646-11649; 2017 Aug 30. PDF

 

11. Luo, X.; Fu, G.; Wang, R.E.; Zhu, X.; Zambaldo, C.; Liu, R.; Liu, T.; Lyu, X.; Du, J.; Xuan, W.; Yao, A.; Reed. S.A.; Kang. M.; Zhang, Y.; Guo, H.; Huang, C.; Yang, P.; Wilsoh, I.A.; Schultz, P.G.; Wang, F. “Genetically Encoding Phosphotyrosine and its Nonhydrolyzable Analog in Bacteria”, Nature Chemical Biology; 13(8):845-849; 2017 August 13. PDF

10. Koh, M., Nasertorabi, F., Stevens, R.C., Schultz, P.G. “Generation of an Orthogonal Protein–Protein Interface with a Non-Canonical Amino Acid”, J. Am. Chem. Soc.; 139(16):5728-5731; 2017 April 26. PDF

 

09. Bollong, M.J., Yang, B., Vergani, N., Beyer, B.A., Chin, E.N., Zambaldo, C., Wang, D., Chatterjee, A.K., Lairson, L.L., Schultz, P.G. “Small Molecule-Mediated Inhibition of Myofibroblast Transdifferentiation for the Treatment of Fibrosis”, Proc. Natl. Acad. Sci. (U.S.A.); 114(18):4679-4684; 2017 April 16. PDF

 

08. Love, M.S.; Beasley, F.C.; Jumani, R.S.; Wright,T.M.; Chatterjee, A.K.; Huston, C.D.; Schultz, P.G.; McNamara, C.W. “A High-Throughput Phenotypic Screen Identifies Clofazimine as a Potential Treatment for Cryptosporidiosis”, PLoS Negl. Trop. Dis.; 11(2):e0005373; 2017 Feb 3. PDF

 

07. Wang, Y.; Du, J.; Zou, H.; Liu, Y.; Zhang, Y.; Gonzalez, J.; Chao, E.; Lu, L.; Parker, H.; Nguyen-Tran, V.; Shen, W.; Wang, D.; Schultz, P.G., Wang, F. "Multifunctional Antibody Agonists Targeting Glucagon-like Peptide-1, Glucagon, and Glucose-dependent Insulinotropic Polypeptide Receptors", Angew. Chem. Int. Ed. Engl; 55(40):12475-8; 2016 Sep 26. PDF

 

06. Cao,Y.; Rodgers, D.T.; Du, J.; Ahmad, I.; Hampton, E.N.; Ma, J.S.; Mazagova, M.; Choi, S.; Yun, H.Y.; Xiao, H.; Yang, P.; Luo, X.; Lim, R.K.V.; Pugh, H.M.; Wang, F.; Kazane, S.A.; Wright, T.M.; Kim, C.H.; Schultz, P.G.; Young, T.S. “Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer”, Angew. Chem. Int. Ed. Engl.; 55(26):7520-4; 2016 Jun 20. PDF

 

05. Liu, T.; Wang, Y.; Luo, X.; Li, J.; Reed, S.A.; Xiao, H.; Young, T.S.; Schultz, P.G. “Enhancing Protein Stability with Extended Disulfide Bonds”, Proc. Natl. Acad. Sci. (U.S.A.); 113(21):5910-5; 2016 May 24. PDF

 

04. Xiao, H., Xuan, W., Shao, S., Liu, T., Schultz, P.G. "Genetic Incorporation of ε-N-2-Hydroxyisobutyryl-lysine into Recombinant Histones", ACS Chem. Bio.; 10(7):1599-603; 2015 April 29. PDF

 

03. Harbut, M., Vilcheze, C., Luo, X., Hensler, M.E., Guo, H., Yang, B., Chatterjee, A.K., Nizet, V., Jacobs, W.R., Schultz, P.G., Wang, F., "Auranofin Exerts Broad-Spectrum Bactericidal Activities by Targeting Thiol-Redox Homeostasis", Proc. Natl. Acad. Sci. (U.S.A.); 112(14):4453-4458; 2015 March 23. PDF

 

02. Wang, R., Liu, T., Wang, Y., Cao, Y., Du, J., Luo, X., Deshmukh, V., Kim, C.H., Lawson, B.R., Tremblay, M.S., Young, T.S., Kazane, S.A., Wang, F., Schultz, P.G., "An Immunosuppressive Antibody-Drug Conjugate", J. Am. Chem. Soc.;137(9):3229-32; 2015 Mar 11. PDF

 

01. Pearson, A.D., Mills, J.H., Song, Y., Nasertorabi, F., Han, G.W., Baker, D., Stevens, R.C., Schultz, P.G., "Trapping a Transition State in a Computationally Designed Protein Bottle", Science; 347(6224):863-7; 2015 Feb 20. PDF