 |
| Born
Beijing, China, 1971. |
| Peking
University, B.S., 1995. |
| Rutgers
University, New Brunswick, M.S., 1997. |
| University
of California, Berkeley, Ph.D., 2003. |
| Harvard
Medical School, Postdoctoral Fellow, 2003-2006. |
| University
of Chicago, Assistant Professor 2006-. |
| |
| Accolades |
| 2006
Camille and Henry Dreyfus New Faculty Award |
|
|
| Jun Yin |
| Assistant
Professor |
|
|
| |
| Research
Interests |
|
The research of our lab is at
the interface of chemistry, biology and medicine. We are working toward:
- Developing new chemical tools
to study biological problems. We are developing new methods for high
throughput profiling of cell signaling networks and for molecular
imaging of biological processes in the living cell.
- Elucidating the biochemical
mechanism of signal transduction mediated by cell surface receptors
such as ErbB receptor tyrosine kinases.
- Enzyme engineering for the
biosynthesis of structurally diversified natural products with new
medicinal activities.
To achieve these goals, our lab develops and employs a wide variety of
biochemical and biophysical methods, including DNA library
construction, phage display, enzyme directed evolution, organic
synthesis, cell culturing, chemical genetics, high throughput
proteomics, enzyme kinetics and molecular imaging. |
| |
| Specific
projects in the lab include: |
| 1)
Signal transduction mechanisms – global profiling of
posttranslational modification enzymes for cell signaling. |
| Communication
and coordination of various cellular events from cell division to
apoptosis depend on the transduction of dynamic cellular signals
encoded by one universal chemical language – protein
posttranslational modification (PTM). For example, PTMs such as
phosphorylation, glycosylation, methylation, acetylation and lipidation
all play central roles mediating signal transduction either by
modulating protein – protein interactions or by affecting the
subcellular localization of the modified proteins. Two major challenges
for mapping the signal transduction networks are: (1) how to identify
from the whole proteome the downstream targets of a PTM enzyme such as
a kinase or a glycosyltransferase and (2) how to identify from the
whole proteome the upstream PTM enzymes that are responsible for a
specific modification such as phosphorylation or glycosylation on a
signaling molecule. We are thus interested in developing high
throughput profiling systems that would allow us to profile the PTM
enzymes in the human genome and address those challenges. |
 |
| |
| 2)
Signal transduction mechanisms – detailed mechanistic studies
on ErbB receptor signaling by photo crosslinking and molecular imaging.
|
| The four
members of the ErbB receptor tyrosine kinases play fundamental roles in
signal transduction cascades controlling tissue growth in both normal
developmental processes and pathological states such as cancer. The
binding of various growth factor ligands to the ErbB receptors elicits
a complex array of receptor homo and heterodimerization and activates
different signaling pathways. Two fundamental questions of the complex
signaling events mediated by ErbB receptors are the focus of our lab:
(1) do different ligands induce different ErbB receptor dimerization
patterns as a way to mediate different signals and (2) do different
combinations of ErbB receptor dimerization have different endocytic
behaviors as a way for fine-tuning the length and the strength of the
mediated signals. To address those questions, ErbB receptors expressed
on the cell surface are site specifically labeled with photo
crosslinking reagents or fluorescent probes in order to study their
interactions with each other and their endocytic pathways. |
 |
| |
| 3)
Enzyme directed evolution – combinatorial biosynthesis of
“unnatural” natural products. |
| Polyketides
and nonribosomal peptides are two large classes of pharmacologically
important natural products as a rich source of anticancer (epothilone,
bleomycin) and antibiotic (vancomycin, erythromycin) agents. The
biosyntheses of these natural products share the same logic by stepwise
chain elongation on multimodular polyketide synthase (PKS) or
nonribosomal peptide synthetase (NRPS) as the enzymatic assembly line
of simple building blocks – carboxylic acids for PKS and
amino acids for NRPS. There has been a great interest for diversifying
the structures of polyketides and nonribosomal peptides in order to
optimize their biological activities. Unfortunately the structural
complexity of these natural products poses a daunting challenge for
total synthesis or chemical modification. We are thus trying to
reprogram the PKS and NRPS assembly lines by enzyme directed evolution
for the biosynthesis of “unnatural” natural
products with redesigned structures and desired biological activities. |
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| Selected
References |
| F. E. Romesberg, B. D. Santarsiero, B. Spiller, J. Yin, D. Barnes, P. G. Schultz, R. C. Stevens, Biochemistry, 1998, 37, 14404. |
| J. Yin, E. C. Mundorff, P. L. Yang, K. U. Wendt, D. Hanway, R. C. Stevens, P. G. Schultz, Biochemistry 2001, 40, 10764. |
| P. G. Schultz, J. Yin, R. A. Lerner, Angew Chem Int Ed Engl 2002, 41, 4427. |
| J. Yin, S. E. Andryski, A. E. t. Beuscher, R. C. Stevens, P. G. Schultz, Proc Natl Acad Sci U S A 2003, 100, 856. |
| J. Yin, A. E. t. Beuscher, S. E. Andryski, R. C. Stevens, P. G. Schultz, J Mol Biol 2003, 330, 651. |
| S. Venkateshrao, J. Yin, A. A. Jarzecki, P. G. Schultz, T. G. Spiro, J Am Chem Soc 2004, 126, 16361. |
| J. Yin, F. Liu, X. Li, C. T. Walsh, J Am Chem Soc 2004, 126, 7754. |
| J. Yin, F. Liu, M. Schinke, C. Daly, C. T. Walsh, J Am Chem Soc 2004, 126, 13570. |
| J. Yin, J. H. Mills, P. G. Schultz, J Am Chem Soc 2004, 126, 3006. |
| S. M. McLoughlin, M. T. Mazur, L. M. Miller, J. Yin, F. Liu, C. T. Walsh, N. L. Kelleher, Biochemistry 2005, 44, 14159. |
| F. H. Vaillancourt, J. Yin, C. T. Walsh, Proc Natl Acad Sci U S A 2005, 102, 10111. |
| J. Yin, A. J. Lin, P. D. Buckett, M. Wessling-Resnick, D. E. Golan, C. T. Walsh, Chem Biol 2005, 12, 999. |
| J. Yin, P. D. Straight, S. M. McLoughlin, Z. Zhou, A. J. Lin, D. E. Golan, N. L. Kelleher, R. Kolter, C. T. Walsh, Proc Natl Acad Sci U S A 2005, 102, 15815. |
| J. Yin, A. J. Lin, D. E. Golan, C. T. Walsh, Nat Protoc 2006, 1, 280. |
| N. J. Marshall, J. Yin, in Chemical Probes and Tags (Ed.: L. M. Miller), Wiley-VCH, Weinheim, 2007. |
| G. M. Singh, F. H. Vaillancourt, J. Yin, C. T. Walsh, Chem Biol 2007, 14, 31. |
| M. Yen, J. Yin, Biotechniques 2007, 43, 31. |
| J. Yin, P. D. Straight, S. Hrvatin, P. C. Dorrestein, S. B. Bumpus, C. Jao, N. L. Kelleher, R. Kolter, C. T. Walsh, Chem Biol 2007, 14, 303. |
| Z. Zhou, P. Cironi, A. J. Lin, Y. Xu, S. Hrvatin, D. E. Golan, P. A. Silver, C. T. Walsh, J. Yin, ACS Chem Biol 2007, 2, 337. |
| M. Sunbul, M. Yen, Y. Zou, J. Yin, Chem Commun (Camb) 2008, 5927. |
| Y. Zou, J. Yin, Chembiochem 2008, 9, 2804. |
| Y. Zou, J. Yin, Bioorg Med Chem Lett 2008, 18, 5664. |
| M. Sunbul, N. J. Marshall, Y. Zou, K. Zhang, J. Yin, J Mol Biol 2009, 387, 883. |
| M. Sunbul, K. Zhang, J. Yin, Methods Enzymol 2009, 458, 255. |
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Organic 