Peter G. Schultz
|Peter G. Schultz|
June 23, 1956 |
|Known for||Chemical Biology|
|Awards||ACS Award in Pure Chemistry (1990)
Wolf Prize (1994)
|Institutions||The Scripps Research Institute,|
|Doctoral advisor||Peter Dervan|
|Other academic advisors||Christopher Walsh|
Peter G. Schultz (born June 23, 1956) is an American chemist. He is the CEO and Professor of Chemistry at The Scripps Research Institute, the founder and former director of GNF, and the founding director of the California Institute for Biomedical Research (Calibr), established in 2012. In August 2014, Nature Biotechnology ranked Schultz the #1 top translational researcher in 2013.
Schultz completed his undergraduate degree from Caltech in 1979 and continued there for his doctoral degree (in 1984) with Peter Dervan. His thesis work focused on the generation and characterization of 1,1-diazenes and the generation of sequence-selective polypyrrole DNA binding/cleaving molecules. He then spent a year at the Massachusetts Institute of Technology with Christopher Walsh before joining the chemistry faculty at the University of California, Berkeley. He became a Principal Investigator of Lawrence Berkeley National Laboratory in 1985 and an investigator of the Howard Hughes Medical Institute in 1994. In 1999 Schultz moved to The Scripps Research Institute and also became founding Director of the Genomics Institute of the Novartis Research Foundation (GNF), which was initiated purely as a genomic research outlet of Novartis, but which grew during Schultz's tenure to include a significant drug discovery effort and more than triple the number of intended employees (currently over 500 people). In March 2010, he left GNF to return to the non-profit sector and founded the California Institute for Biomedical Research (Calibr) in March 2012. He has trained over 300 graduate students and postdoctoral fellows, many of whom are on the faculties of major research universities.
Combinatorial chemistry and molecular evolution
Schultz's work consists of finding ways to do a great many similar experiments at the same time, on many different compounds. He is one of the leading pioneers in combinatorial chemistry, screenable molecular libraries, and "high-throughput" chemistry. His interests are extremely wide-ranging, with applications in such diverse areas as catalytic mechanisms, cell-specialization and other complex biological processes (normally studied by biologists, not chemists), basic photochemistry, biophysical probes of all stripes from NMR through positron-emission, and solid-state materials science.
Early in his career Schultz showed that the natural molecular diversity of the immune system could be directed to generate catalytic antibodies. This method enabled the subsequent development of many new selective enzyme-like catalysts for reactions ranging from acyl transfer and redox reactions to pericyclic and metalation reactions. Although their catalytic activities are only rarely strong enough to be of practical use, catalytic antibodies have provided important new insights in our understanding of biocatalysis, structural plasticity of proteins, evolution of biochemical function, and the immune system itself.
Schultz then applied molecular diversity—the strategy of creating a large community of different molecules, plus a method for fishing out and identifying the ones that do what you want—to a range of problems in chemistry, biology and materials science. Along with Richard Lerner, he was one of the critical players in the development of phage-display libraries, and surface-library chips. For high-throughput bioassays which require freely soluble test-compounds, he uses microrobotic fluid-manipulation systems, adapted for 1,536-microwell cell-culture plates, to separately treat very small cell colonies with large numbers (hundreds of thousands) of different compounds.
Using these various high-throughput and combinatorial experimental approaches, Schultz has identified materials with novel optical, electronic, and catalytic properties; also, proteins and small molecules which control important biological processes such as aging, cancer, autoimmunity, and stem-cell differentiation and de-specialization back to pluripotency.
Unnatural amino acids
Schultz has pioneered a method for adding new building blocks, beyond the common twenty amino acids, to the genetic codes of prokaryotic and eukaryotic organisms. This is accomplished by screening libraries of mutant amino acyl tRNA synthetases for mutants which charge nonsense-codon tRNAs with the desired unnatural amino acid. The organism which expresses such a synthetase can then be genetically programmed to incorporate the unnatural amino acid into a desired protein in the usual way, with the nonsense codon now coding for the unnatural amino acid. Normally, the unnatural amino acid itself must be synthesized in the lab and supplied to the organism by adding it to the organism's growth medium. The unnatural amino acid must also be able to pass through the organism's cell membrane into the interior of the organism.
More than seventy unnatural amino acids have been genetically encoded in bacteria, yeast, and mammalian cells, including photoreactive, chemically reactive, fluorescent, spin-active, sulfated, pre-phosphorylated, and metal-binding amino acids. This technology allows chemists to probe, and change, the properties of proteins, in vitro or in vivo, by directing novel, lab-synthesized chemical moieties specifically into any chosen site of any protein of interest.
A bacterial organism has been generated which biosynthesizes a novel, previously unnatural amino acid (p-aminophenylalanine) from basic carbon sources and includes this amino acid in its genetic code. This is the first example of the creation of an autonomous twenty-one-amino-acid organism.
Chemistry and cell biology
A significant effort of the Schultz laboratory in recent years has been to screen small molecule libraries in a diversity of cell based assays to identify compounds that control cell fate. Examples of such compounds identified include:
- stauprimide, a molecule priming stem cells for differentiation
- stemregenin 1 (SR1), an AhR antagonist that expands hematopoietic stem cells ex vivo.
- kartogenin, a CBFβ activator that induces cartilage differentiation in vivo.
- TCA1, a dual DprE1-MoeW inhibitor capable of killing both drug-resistant and persistent tuberculosis, now in the TB Alliance pipeline.
Schultz has authored more than 500 papers in peer-reviewed scientific journals, including many in the most prestigious scientific journals: Science, Proceedings of the National Academy of Sciences of the United States of America, and the Journal of the American Chemical Society. He is on many editorial boards.
Schultz has had to retract four papers published in three of the highest-profile scientific journals: one in Science, one in Proceedings of the National Academy of Sciences, and two in Journal of the American Chemical Society. The retraction in Science and one of the retractions in JACS concerned an attempt to incorporate unnatural pre-glycosylated amino acids into the genetic vocabulary of a cell (see the above section on unnatural amino acids); the retraction in PNAS and the other retraction in JACS were about mutations which make antibodies stable at higher-than-normal temperatures.
- 2016 Heinrich Wieland Prize
- 2013 The Laureate Chemistry for the Future Solvay Prize
- 2006 ACS Arthur C. Cope Award
- 2002 Paul Ehrlich and Ludwig Darmstaedter Award
- 2000 ACS Alfred Bader Award in Bioorganic Chemistry
- 1998 NSF Alan T. Waterman Award
- 1995 honorary doctorate from the Faculty of Science and Technology at Uppsala University, Sweden 
- 1994 Wolf Prize in Chemistry
- 1992 Protein Science Young Investigator Award from the Protein Society
- 1992 UC Berkeley College of Chemistry Teaching Award
- 1991 Eli Lilly Award in Biological Chemistry
- 1990 ACS Award in Pure Chemistry
- "Scripps Research Institute Names Peter Schultz as CEO, Steve Kay as President".
- Curriculum Vitae
- Proc Natl Acad Sci U S A. 2009 June 2; 106(22): 8912–8917. doi:10.1073/pnas.0903860106.
- J Am Chem Soc. 2003 Jan 29;125(4):935-9. Generation of a bacterium with a 21 amino acid genetic code. Mehl RA, Anderson JC, Santoro SW, Wang L, Martin AB, King DS, Horn DM, Schultz PG.
- Chen, Shuibing. "Dedifferentiation of Lineage-Committed Cells by a Small Molecule". Journal of the American Chemical Society. 126 (2): 410–411. doi:10.1021/ja037390k.
- Zhu, S; Wurdak, H; Wang, J; et al. (2009). "A small molecule primes embryonic stem cells for differentiation". Cell stem cell. 4 (5): 416–26. PMID 19427291. doi:10.1016/j.stem.2009.04.001.
- "PNAS retracts paper linked to ex-Ohio State researcher who had chemistry PhD revoked - Retraction Watch". Retraction Watch. 1 September 2017.