The Peter G. Schultz Laboratory

Welcome to the Schultz Lab

The focus of our research is on synthesis of molecules and molecular assemblies with novel physical, chemical or biological properties and functions. 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 (molecular recognition) and enzymes (catalysis) to the photosynthetic center (energy harvesting). Given Nature's "synthetic" prowess, we have undertaken a biologically inspired approach to synthesis in which the molecules and processes of living organisms are combined with the principles and tools of 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.

The above theme runs throughout all of the projects in the lab. Current efforts focus on: (1) the generation of catalytic antibodies and the characterization of their mechanisms and immunological evolution; (2) the development and application of general methods to add unnatural amino acids with novel chemical, biological, and physical properties to the genetic codes of living organisms; (3) the application of combinatorial methods to the generation of small molecules, proteins, nucleic acids, and even solid state materials with novel properties; (4) the application of chemical and genomics tools (including the use of arrayed small molecule, siRNA and cDNA libraries in cellular pathway and phenotypic screens and protein/mRNA expression profiling) to better understand and ultimately control (both in vitro and in vivo) the biological processes involved in stem cell self renewal, differentiation and cellular reprogramming; and (5) early stage translational research focused on regenerative medicine, cancer, autoimmune, metabolic, and orphan/neglected diseases.

Group Information

The group occupies 10,000 square feet of laboratory space in the Stein Clinical Research Center, adjacent to the Beckman Center for Chemical Sciences. The lab currently consists of roughly 25 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

1.	Liu, C.C., Mack, A.V., Tsao, M-L., Mills, J.H., Lee, H., Choe, H., Farzan, M., Schultz, P.G., Smider, V.V. "Protein Evolution with an Expanded Genetic Code." Proc. Natl. Acad. Sci., 105(46):17688-93, 2008.
2.	Lee, H.S., Spraggon, G., Schultz, P.G., Wang, F. "Genetic Incorporation of a Metal-ion Chelating Amino Acid into Proteins as a Biophysical Probe." J. Am. Chem. Soc., 131(7):2481-2483, 2009.
3.	Zhu, S., Wurdak, H., Wang, J., Lyssiotis, C.A., Peters, E.C., Cho, C., Wu, X., Schultz, P.G. "A small molecule primes embryonic stem cells for differentiation." CellStemCell, 4:416-426, 2009.
4.	Wu, X., Schultz, P.G. "Synthesis at the Interface of Chemistry and Biology." J. Am. Chem. Soc., 131(35):12497-515, 2009.
5.	Lee, H.S., Guo, J., Lemke, E., Dimla, R., Schultz, P.G. "The Genetic Incorporation of a Small, Environmentally Sensitive, Fluorescent Probe into Proteins in Saccharomyces Cerevisiae." J. Am. Chem. Soc., 131(36):12921-3, 2009.
6.	Liu, C.C., Choe, H., Farzan, M., Smider, V.V., Schultz, P.G. "Mutagenesis and Evolution of Sulfated Antibodies using an Expanded Genetic Code." Biochemistry, 48(37):8891-8, 2009.
7.	Wurdak, H., Romero, A., Zhu, S., Lorger, M., Watson, J., Chiang, C., Zhang, J., Natu, V.S., Tu, B.P., Walker, J., Harsh, G.R., Felding-Habermann, B., Orth, A.P., Miraglia, L.J., Rines, D.R., Skirboll, S.L., Schultz, P.G. "An RNAi screen identifies TRRAP as a regulator of brain tumor-initiating cell differentiation." Cell Stem Cell, 6(1):37-47, 2010.
8.	Liu, C.C., Schultz, P.G. "Adding new chemistries to the genetic code." Ann. Rev Biochem, 79:413-44, 2010.
9.	Boitano, A.E., Wang, J., Romeo, R., Bouchez, L.C., Parker, A., Sutton, S., Walker, J.R., Tellew, J., Denision, M., Cooke, M.P., Schultz, P.G. "Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells." Science, 329(5997):1345-8, 2010.
10.	Wurdak, H., Zhu, S., Min, K.H., Aimone, L., Lairson, L.L., Watson, J., Chopiuk, G., Demas, J., Charette, B., Halder, R., Weerapana, E., Cravatt, B.F., Cline, H.T., Peters, E.C., Zhang, J., Walker, J.R., Wu, C., Chang, J., Tuntland, T., Cho, C.Y., Schultz, P.G. "A small molecule accelerates neuronal differentiation in the adult rat." Proc. Nat. Acad. Sci., 107(38):16542-7, 2010.
11.	Lyssiotis, C.A., Lairson, L.L., Boitano, A.E., Wurdak, H., Zhu, S., Schultz, P.G. "Chemical Control of Stem Cell Fate and Developmental Potential." Angew. Chem., 50(1):200-42, 2011.
12.	Young, T.S., Young. D.D., Ahmad, I., Louis, J.M., Benkovic, S.J., Schultz, P.G. "The Evolution of Cyclic Peptide Protease Inhibitors." Proc. Nat. Acad. Sci., 108(27):11052-11056, 2011.
13.	Gauba, V., Grunewald, J., Gorney, V., Deaton, L., Kang, M., Bursulaya, B., Ou, W., Lerner, R.A., Schmedt, C., Geierstanger, B.H., Schultz, P.G., Ramirez-Montagut, T. "Loss of CD4 T-cell dependent tolerance to proteins with modified amino acids." Proc. Nat. Acad. Sci., 108(31):12821-6, 2011.
14.	Liu, J., Johnson, K., Li, J., Piamonte, V., Steffy, B.M., Hsieh, M., Ng, N., Zhang, J., Walker, J.R., Ding, S., Muneoka, K., Wu, X., Glynne, R., Schultz, P.G. "A Regenerative Phenotype in Mice with a Point Mutation in TGFBR1." Proc. Nat. Acad. Sci., 108(35):14560-5, 2011.
15.	Kazane, S.A., Sok, D., Uson, M.L., Cho, E.H., Kuhn, P., Schultz, P.G., Smider, V.V. "Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR." Proc. Nat. Acad. Sci., 109(10):3731-6, 2012.
16.	Johnson, K., Zhu, S., Tremblay, M., Payette, J.N., Wang, J., Bouchez, L.C., Meeusen, S., Althage, A., Cho, C., Wu, X., Schultz, P.G. "A stem cell-based approach to cartilage repair." Science, 336(6082):717-2, 2012.
17.	Hirota, T., Lee, J.W., St. John., P.C., Sawa, M., Iwaisako, K., Noguchi, T., Pongsawakul, P.Y., Sonntag, T., Welsh, D.K., Brenner, D.A., Doyle, J., Schultz, P.G., Kay, S.A. "Identification of Small Molecule Activators of Cryptochrome." Science, 337(6098):1094-1097, 2012.
18.	Kim, C., Axup, J.Y., Dubrovska, A., Kazane, S.A., Hutchins, B.A., Wold, E., Smider, V.V., Schultz, P.G. "Synthesis of Bispecific Antibodies with Genetically Encoded Unnatural Amino Acids." J. Am. Chem. Soc., 134(24):9918-21, 2012.
19.	Axup, J.A., Bajjuri, K.M., Ritland, M., Hutchins, B.M., Kim, C., Kazane, S.A., Halder, R., Forsyth, J.S., Santidrian, A.F., Stafin, K., Liu, Y., Tran, H., Seller, A.J., Biroc, S.L., Szydlik, A., Pinkstaff, J.K., Tian, F., Sinha, S.C., Felding-Habermann, B., Smider, V.V., Schultz, P.G. "Synthesis of Site-specific Antibody-Drug Conjugates Using Unnatural Amino Acids." Proc. Nat. Acad. Sci., 109(40):16101-16106, 2012.
20.	Wang, F., Sambandan, D., Halder, R., Wang, J., Batt, S., Weinrick, B.C., Ahmad, I., Yang, P., Zhang, Y., Kim, J., Hassani, M., Huszar, S., Trefzer, C., Chatterjee, A., Johnsson, K., Mikusove, K., Besra, G., Futterer, K., Jacobs, W.R., Schultz, P.G. "Identification of a Small Molecule with Activity Against Drug-resistent and Persistent Tuberculosis." , submitted, 2012.
21.	Wang, F., Sen, S., Zhang, Y., Ahmad, I., Zhu, X., Wilson, I.A., Smider, V.V., Magliery, T.J., Schultz, P.G. "Somatic Hypermutation Maintains Antibody Thermodynamic Stability During Affinity Maturation." , submitted, 2012.
22.	de Lichtervelde, L., Boitano, A.E., Wang, Y., Krastel, P., Petersen, F., Cooke, M.P., Schultz, P.G. "Eupalinilide E inhibits erythropoiesis and promotes the expansion of hematopoietic progenitor cells." , submitted, 2013.
23.	Deshmukh, V.A., Lyssiotis, C.A., Tardif, V., Swoboda, J., Ahmad, I., Kondo, T., Theofilopoulos, A.N., Lawson, B.R., Lairson, L.L., Schultz, P.G. "Endogenous Adult Stem Cells as a Therapeutic Approach to Demyelinating Diseases." , submitted, 2012.