Download OMB No. 0925-0001/0002 (Rev. 08/12), Biographical Sketch Format

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BIOGRAPHICAL SKETCH
NAME: James R Swartz
eRA COMMONS USER NAME (credential, e.g., agency login): Swartz.James
POSITION TITLE: Professor, Dept. of Chemical Engineering and Dept. of Bioengineering
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
South Dakota School of Mines and Technology
MIT
MIT
DEGREE
(if applicable)
B.S.
M.S.
D.Sc.
Completion
Date
MM/YYYY
05/1971
05/75
10/78
FIELD OF STUDY
Chemical Engineering
Chemical Engineering
Biochemical Engineering
A. Personal Statement
The goal of this project is to enrich biotechnology training for the trainees as well as for the entire Stanford
community. Although Bio-X has a similar mission, it uses very different mechanisms and does not have a central
focus on nurturing students. I have been associated with this program since its inception in 1991; first as a
Genentech employee and then as a Stanford faculty member. I have witnessed and enjoyed the positive impact it
has had on the trainees and on our community. I worked hard to continue and improve the program over the last
funding period, and I am very grateful that Professor Cochran has agreed to assume the role of Program Director. I
have worked with her and will continue to help in facilitating an effective hand-off. I am also very committed to
helping to improve and expand this program. It can bring tremendous benefits for applied medical research and
training here at Stanford as well as providing benefits to the broader community at Stanford and the surrounding
area.
B. Positions and Honors
Professional Experience
‘71-’73 Union Oil of California; Petroleum and Chemical Engineering
‘73-’78 MIT Research Assistant; Affinity Purification, Computer Control of Yeast Continuous Culture
‘79-’81 Eli Lilly and Co.; Sr. Scientist, Antibiotic Ferm. Development; Cont. Culture of rDNA E.coli
‘81-’82 Genentech, Inc.; Scientist, rDNA Fermentation Process Development and Scale-up
‘82-’88 Genentech, Inc.; Director, Fermentation Process Research and Development
‘88-’98 Genentech, Inc.; Sr. Scientist and Staff Scientist, Integrated Ferm. Process Design and Scale-up
including vector and organism design combining Biochemistry, Genetics, and Biochem. Eng.
’98-‘04 Stanford University, Professor of Chemical Engineering with emphasis on Biochemical Engineering
’04-Present Stanford University, Professor of Chemical Engineering and Professor of Bioengineering
’07-’09 Stanford University, The Leland T. Edwards Professor of Engineering
’09-Present Stanford University, James H. Clark Professor of Engineering
Honors and Awards
’76 Pfizer Fellowship in Biochemical Engineering
’77 Florasynth Fellowship, Institute of Food Technologists
’91 Served on National Research Council Committee on Bioprocess Engineering
’92 Keynote Address at Inaugural Meeting of The American Institute of Medical and Biological Engineers ’93
Inducted as Founding Fellow, The American Institute of Medical and Biological Engineers
’93 James Van Lanen Service Award from the Division of Biochemical Technology, American Chem. Soc.
’94 Keynote Address at Asia-Pacific Biochemical Engineering Conference
’94 Keynote Address, Biotech 2000 Meeting, Seoul, Korea ’97
Co-Chair of Biochemical Engineering X
’99 Elected to National Academy of Engineering
’02 Opening Keynote Lecture, 2nd Intl Conf: rDNA Production with Prok and Euk Host Cells, Cernobbio, Italy. ’05
Amgen Award, Society of Industrial Microbiology
’05 Distinguished Alumnus Award, S.Dak. School of Mines and Technology ’06
Gaden Award
’06 Leland T. Edwards Professor in the School of Engineering
’07 Keynote Lecture, 20th Meeting of the European Society for Animal Cell Tech, 2007, Dresden, Germany
’07 Opening Keynote Speaker, Recent Advances in Ferm Tech (RAFT VII), 2007, St. Pete Beach, Florida
’08 The James Bailey Award, Soc for Biol. Eng. (Am Inst. For Chem. Eng.)
’08 One of 100 Chemical Engineers of the Modern Era, American Institute of Chemical Engineers
’09 Inaugural Fellow of the American Chemical Society
’11 Keynote speaker, New Biotech Production Systems, Dechema, Frankfurt, Germany
’12 Daniel I.C. Wang Award for Biochemical Engineering Excellence, ACS, AIChE, SBE
’12 Texas Distinguished Faculty Lectureship, UT, Austin
‘14 Allen P. Colburn Honorary Lecturer, DuPont; June 2014
’14 Keynote Speaker, Fraunhofer Forum International Symposium on Cell-free Protein Synthesis, Berlin
C. Contribution to Science
1. Pioneering development of versatile, practical cell-free protein synthesis technology. Primarily started after I
came to Stanford in 1998, the program focused on developing a complete technology package for the
industrial production of pharmaceutical proteins. The major advance was gaining control over cell-free
metabolism. Initially cofactors were added to activate the conversion of pyruvate to acetyl CoA as an ATP
source. This was expanded to include oxidative phosphorylation using reducing equivalents from glucose,
pyruvate, or glutamate metabolism after developing a chemical environment that mimicked the E.coli
cytoplasm. Chromosomal deletions stabilized the amino acids. Oxidative protein folding was activated by
inactivating the reducing pathway (glutathione and thioredoxin reductases) and adding a disulfide isomerase.
Rapidly growing cells provided the most productive extracts, and a computer controlled fermentation protocol
was developed to complement a specially designed defined medium. Antifoam agents allow air sparging to
deliver the required oxygen without disrupting protein synthesis or folding. Finally, non-natural amino acids
were incorporated either site specifically using orthogonal tRNA and tRNA synthetase pairs or by methionine
replacement. This complete technology package provided the basis for the founding of Sutro Biopharma, a
company recently recognized as one of the leading small biotechnology companies. Sutro has major
contracts with Cellgene and with Merck-Serono and will be in the clinic next year with novel antibody drug
conjugate and bispecific antibody drug candidates.
1. Yang J, Kanter G, Voloshin A, Levy R, Swartz JR. Expression of active murine granulocyte-macrophage
colony-stimulating factor in an Escherichia coli cell-free system. Biotechnol Prog. 2004
Nov-Dec;20(6):1689-96. PubMed PMID: 15575700.
2. Goerke AR, Swartz JR. Development of cell-free protein synthesis platforms for disulfide bonded
proteins. Biotechnol Bioeng. 2008 Feb 1;99(2):351-67. PubMed PMID: 17626291.
3. Goerke AR, Swartz JR. High-level cell-free synthesis yields of proteins containing site-specific
non-natural amino acids. Biotechnol Bioeng. 2009 Feb 1;102(2):400-16. PMID: 18781689.
4. Lui BH, Cochran JR, Swartz JR. Discovery of improved EGF agonists using a novel in vitro screening
platform. J Mol Biol. 2011 Oct 21;413(2):406-15. Epub 2011 Aug 23. PubMed PMID: 21888916.
5. Albayrak C, Swartz JR. Cell-free co-production of an orthogonal transfer RNA activates efficient
site-specific non-natural amino acid incorporation. Nucleic Acids Res. 2013 Jun;41(11):5949-63. doi:
10.1093/nar/gkt226. Epub 2013 Apr 15. PubMed PMID: 23589624; PMCID: PMC3675464.
2. Pioneering invention of cell-free metabolic engineering. This development grew out of the metabolic
advances described above for cell-free protein synthesis. After oxidative phosphorylation was activated
cell-free reactions, radioactive glutamate metabolism was used to show that the TCA cycle, amino acid
(aspartic acid) and other metabolic processes were occurring robustly in the absence of intact cell. A
complete genomic survey ( 4000 genes; as yet unpublished) was also conducted in which a single protein
was enriched in each cell-free reaction and its effect on protein synthesis was determined. This identified 139
proteins with significant effects on protein synthesis. Many of these influenced ATP supply, further showing
that complex metabolic pathways were active. This realization motivated the founding of GreenLight
Biosciences, a company that is now at the 1000 liter scale producing a complex nutraceutical using cell-free
metabolism. Several collaborative agreements are also in place for additional products.
1. Jewett MC, Swartz JR. Mimicking the Escherichia coli cytoplasmic environment activates long-lived and
efficient cell-free protein synthesis. Biotechnol Bioeng. 2004 Apr 5;86(1):19-26. PMID: 15007837.
2. Calhoun KA, Swartz JR. An economical method for cell-free protein synthesis using glucose and
nucleoside monophosphates. Biotechnol Prog. 2005 Jul-Aug;21(4):1146-53. PubMed PMID: 16080695.
3. Calhoun KA, Swartz JR. Energy systems for ATP regeneration in cell-free protein synthesis reactions.
Methods Mol Biol. 2007;375:3-17. Review. PubMed PMID: 17634594.
4. Knapp KG, Goerke AR, Swartz JR. Cell-free synthesis of proteins that require disulfide bonds using
glucose as an energy source. Biotechnol Bioeng. 2007 Jul 1;97(4):901-8. PubMed PMID: 17154312.
5. Jewett MC, Calhoun KA, Voloshin A, Wuu JJ, Swartz JR. An integrated cell-free metabolic platform for
protein production and synthetic biology. Mol Syst Biol. 2008;4:220. doi: 10.1038/msb.2008.57. Epub
2008 Oct 14. PubMed PMID: 18854819; PubMed Central PMCID: PMC2583083.
3. Foundational advances toward novel, highly defined, modular vaccines. This program began with a
collaboration with Ron Levy, then Chair of Oncology in our Medical School, and his wife, Shoshana. They
provided immunology and animal testing expertise with a focus on curing lymphomas with patient-specific
vaccines. We initially developed scFv-GMCSF fusion protein vaccines which were produced in cell-free
reactions with full scFv adhesion and GMCSF activity. These vaccines were effective in mice both for eliciting
antibody responses and for protecting against tumor challenges. With the failure of Genitope and Favrille
clinical trials (using glutaldehyde crosslinked KLH/antibody complex), we were motivated to develop more
effective vaccine designs that could still be supplied at patient-specific vaccines. HepBcore VLPs proved to
provide the best scaffolding for a viral mimic nanoparticle, modular design. Uniquely reactive non-natural
amino acid incorporation allows the co-attachment of the scFv antigen and immune stimulating molecules
with the desired presentation. Three mouse studies (not yet published) now firmly show that these are very
effective designs for eliciting IgG2 antibodies that protect against tumor challenge. This technology is now
being developed by Bullet Biotechnology with a target for initial clinical testing in lymphoma victims next year.
1. Bundy BC, Franciszkowicz MJ, Swartz JR. Escherichia coli-based cell-free synthesis of virus-like
particles. Biotechnol Bioeng. 2008 May 1;100(1):28-37. PubMed PMID: 18023052.
2. Patel KG, Swartz JR. Surface functionalization of virus-like particles by direct conjugation using
azide-alkyne click chemistry. Bioconjug Chem. 2011 Mar 16;22(3):376-87. PMID: 21355575.
3. Ng PP, Jia M, Patel KG, Brody JD, Swartz JR, Levy S, Levy R. A vaccine directed to B cells and produced
by cell-free protein synthesis generates potent antilymphoma immunity. Proc Natl Acad Sci U S A. 2012
Sep 4;109(36):14526-31. PMID: 22875703; PubMed Central PMCID: PMC3437846.
4. Lu Y, Welsh JP, Chan W, Swartz JR. Escherichia coli-based cell free production of flagellin and ordered
flagellin display on virus-like particles. Biotechnol Bioeng. 2013 Aug;110(8):2073-85. doi:
10.1002/bit.24903. Epub 2013 May 1. PubMed PMID: 23519642.
5. Lu Y, Welsh JP, Swartz JR. Production and stabilization of the trimeric influenza hemagglutinin stem
domain for potentially broadly protective influenza vaccines. Proc Natl Acad Sci U S A. 2014 Jan
7;111(1):125-30. PMID: 24344259; PubMed Central PMCID: PMC3890838.
4. Fundamental advances in the biochemistry of [FeFe]hydrogenase maturation and structure function
relationships. Although not directly health related, this work has provide basic insights into novel biochemical
reactions. The project focuses on a very complex enzyme, an [FeFe]hydrogenase with six Fe-S centers and
active site that contains –CO and -CN- adducts was well as an S-C-N-C-S bridging ligand between the two
irons of the active site. Early on, we learned to synthesize and activate this enzyme in our cell-free protein
synthesis reactions as a basis for screening large libraries of mutated enzymes to search for oxygen tolerant
mutants that could couple with photosynthesis and to provide better understanding of enzyme mechanisms.
We also developed the first in vitro hydrogenase activation system. This allowed us to study the requirements
for enzyme activation and, as we learned more, to precisely incorporated isotopic labels useful for FTIR and
EPR analyses. This platform has now revealed new, unique chemical reactions that extract –CO and –CN
from tyrosine and that begin to build the complex active site cofactor. Initially, hydrogenase activation
required the addition of E.coli cell extract. Recently, we have determined that the E.coli proteins, Frataxin (an
iron carrying protein) and, surprisingly, Thioredoxin-1, are beneficial for hydrogenase maturation
(unpublished) so that we now have a fully defined maturation system for further studies and better controlled
sample preparation.
1. Kuchenreuther JM, Stapleton JA, Swartz JR. Tyrosine, cysteine, and S-adenosyl methionine stimulate in
vitro [FeFe] hydrogenase activation. PLoS One. 2009 Oct 26;4(10):e7565. PMID: 19855833.
2. Kuchenreuther JM, George SJ, Grady-Smith CS, Cramer SP, Swartz JR. Cell-free H-cluster synthesis
and [FeFe] hydrogenase activation: all five CO and CN⁻ ligands derive from tyrosine. PLoS One.
2011;6(5):e20346. PubMed PMID: 21673792; PubMed Central PMCID: PMC3105041.
3. Kuchenreuther JM, Myers WK, Stich TA, George SJ, Nejatyjahromy Y, Swartz JR, Britt RD. A radical
intermediate in tyrosine scission to the CO and CN- ligands of FeFe hydrogenase. Science. 2013 Oct
25;342(6157):472-5. doi: 10.1126/science.1241859. PubMed PMID: 24159045.
4. Kuchenreuther JM, Myers WK, Suess DL, Stich TA, Pelmenschikov V, Shiigi SA, Cramer SP, Swartz JR,
Britt RD, George SJ. The HydG enzyme generates an Fe(CO)2(CN) synthon in assembly of the FeFe
hydrogenase H-cluster. Science. 2014 Jan 24;343(6169):424-7. PubMed PMID: 24458644.
5. Dinis P, Suess DL, Fox SJ, Harmer JE, Driesener RC, De La Paz L, Swartz JR, Essex JW, Britt RD,
Roach PL. X-ray crystallographic and EPR spectroscopic analysis of HydG, a maturase in
[FeFe]-hydrogenase H-cluster assembly. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1362-7. PubMed
PMID: 25605932; PubMed Central PMCID: PMC4321296.
The following is the URL to My Bibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/james.swartz.1/bibliography/48041958/public/?sort=date&directio
n=ascending.
D. Research Support
Stanford Bio-X IIP Program
Kim (PI) Swartz (Co-PI)
Initial Feasibility for a Novel AIDS Vaccine
Role: Co-PI (Developing and producing novel vaccines)
10/1/14- 9/30/16
DOE-SC002010
Swartz (PI)
09/15/12-09/14/16
U.S. Department of Energy – Bioenergy Sciences Program
Office of Science Financial Assistance Program
Using In Vitro Maturation and Cell-free Evolution to Understand [FeFe]hydrogenase Activation and Active Site
Constraints. The overall goal is to better understand the assembly and function of these complex catalysts.
Role: PI
The Stanford Global Climate and Energy Project
Swartz (PI)
09/01/2011-08/31/2015
Efficient, Highly Productive Hydrogen Production from Glucose
This project deals with the effective transfer of electrons from NADPH to the hydrogenase enzyme in order of
produce hydrogen. This GCEP sponsored project seeks to develop an effective industrial process that uses cell
extracts to generate hydrogen from glucose with high volumetric productivity and high conversion efficiency.
Role: PI
Role: PI
Stanford Bio-X IIP Program
Swartz (PI)
10/01/12-09/30/15
Building Genetic Tools to Engineer Cyanobacteria
This project will develop improved reagents and methods for the lysis and transformation of cyanobacteria as well
as controllable promoters, a ribosome binding site library, and methods for measuring chromosomal and plasmid
copy number.
Role: PI
CBET 1264289
Swartz (PI)
04/2013-03/2016
NSF: Engineering an Efficient Electron Pathway for Photosynthetic Hydrogen Production
This project is aimed at developing a new electron transport pathway between the photosystem and an [Fe-Fe]
hydrogenase in photosynthetic bacteria.
Role: PI
Completed Research Support
2T32GM008412
Swartz (PI)
07/01/09-03/31/15
NIH/NRSA Institutional Predoctoral Training Grant T32
Biotechnology Training Grant. The goal of this program is to provide a rich educational experience for selected
biotechnology graduate students including: more active interactions with students working on a broad range of
projects, industrial internships, more active mentorship, bioethics education, and other enrichment activities.
Role: PI
Project PC094061
Swartz (PI)
4/1/10-3/31/13
Department of Defense (CDMRP)
“SPIO-loaded VLPs as Contrast Agents for Prostate Cancer”
This project seeks to develop new VLPs that specifically adhere to prostate cancer cells to deliver iron oxide
nanoparticles to these cells so that tumors can be sensitively detected using MRI techniques.
Role: PI