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James K. ChenAcademic Appointments
Appointment
Organization
Assistant Professor
Assistant Professor (By courtesy)
Chemistry
Member
Member
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Curriculum Vitae PDF
Honors & Awards
Title
Organization
Date(s)
NIH Director's Pioneer Award
NIH
2008-2013
Brain Tumor Society Rachel Molly Markoff Research Chair
Brain Tumor Society/Rachel Molly Markoff Foundation
2006-2008
Astellas USA Foundation Award
Astella USA Foundation
2005-2006
Terman Fellow
Stanford University
2005-2008
Basil O'Connor Starter Scholar Research Award
March of Dimes
2005-2007
9 honors and awards: view full list
Administrative Appointments
Title
Organization
Start Year
End Year
Faculty Director
Stanford High-Throughput Bioscience Center
2003
-
Professional Education
Degree
Awarding Institution
Field of Study
Year of Graduation
A.B.
Harvard College
Chemistry
1991
Ph.D.
Harvard University
Chemistry and Chemical Biology
1998
Postdoctoral Fellow
Johns Hopkins School of Medicine
Molecular Biology and Genetics
2003
Postdoctoral Advisees
Brian Feng,
Joel Hyman,
Cory Ocasio
Web Site Links
Research/Lab website:
Personal Web site
Research Interests
The Chen laboratory studies the molecular events that regulate embryonic development and tumorigenesis, using synthetic chemistry, biochemistry, genetics, and embryology. Our research group is currently investigating the Hedgehog pathway, a signaling cascade that is involved in patterning of multiple tissues such as the neural tube, limbs, and somites. Aberrant Hedgehog pathway activation in children and adults is also linked to several cancers, including those of the skin, brain, and gut.
How cells respond to Hedgehog proteins is of particular interest to us, especially since there is recent evidence that Hedgehog signaling in vertebrates has mechanistically diverged from that in invertebrate organisms. Our efforts to gain molecular insights into this pathway involve several strategies. First, several chemicals that specifically perturb the Hedgehog pathway have been discovered, most notably the plant-derived alkaloid cyclopamine, which caused outbreak of cyclopia among grazing livestock in the 1950s. By determining the cellular targets of these small molecules we hope to better understand the biochemical mechanisms that control Hedgehog pathway activation. In addition, we are currently screening chemical libraries for additional Hedgehog signaling modulators with novel modes of action. Second, new putative Hedgehog signaling proteins have been discovered through mouse mutagenesis studies; however, how these proteins interact with other pathway components is not known. We are therefore interrogating the function of these genes in zebrafish, since this model vertebrate organism is compatible with genetic, biochemical, and chemical approaches. Third, we are developing screens for new Hedgehog components using cell culture models of this pathway and genomic libraries.
Our laboratory is also interested in how the Hedgehog pathway regulates tissue patterning and oncogenesis in vertebrates. Using both genetic and chemical perturbations of Hedgehog signaling, we are studying cell migration processes and tumor formation in zebrafish. These investigations have concurrently involved the development of new technologies for gene regulation in this model organism, including a chemically inducible gene expression system and reagents for conditional gene silencing. These methods will be used to evaluate the role of individual Hedgehog pathway components in embryonic development, and their generality promises to provide new research opportunities for the zebrafish community.
How cells respond to Hedgehog proteins is of particular interest to us, especially since there is recent evidence that Hedgehog signaling in vertebrates has mechanistically diverged from that in invertebrate organisms. Our efforts to gain molecular insights into this pathway involve several strategies. First, several chemicals that specifically perturb the Hedgehog pathway have been discovered, most notably the plant-derived alkaloid cyclopamine, which caused outbreak of cyclopia among grazing livestock in the 1950s. By determining the cellular targets of these small molecules we hope to better understand the biochemical mechanisms that control Hedgehog pathway activation. In addition, we are currently screening chemical libraries for additional Hedgehog signaling modulators with novel modes of action. Second, new putative Hedgehog signaling proteins have been discovered through mouse mutagenesis studies; however, how these proteins interact with other pathway components is not known. We are therefore interrogating the function of these genes in zebrafish, since this model vertebrate organism is compatible with genetic, biochemical, and chemical approaches. Third, we are developing screens for new Hedgehog components using cell culture models of this pathway and genomic libraries.
Our laboratory is also interested in how the Hedgehog pathway regulates tissue patterning and oncogenesis in vertebrates. Using both genetic and chemical perturbations of Hedgehog signaling, we are studying cell migration processes and tumor formation in zebrafish. These investigations have concurrently involved the development of new technologies for gene regulation in this model organism, including a chemically inducible gene expression system and reagents for conditional gene silencing. These methods will be used to evaluate the role of individual Hedgehog pathway components in embryonic development, and their generality promises to provide new research opportunities for the zebrafish community.
Publications
- Low WC, Wang C, Pan Y, Huang XY, Chen JK, Wang B "The decoupling of Smoothened from Galphai proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning." Dev Biol 2008; 321: 1: 188-96 More »
- Esengil H, Chen JK "Gene regulation technologies in zebrafish." Mol Biosyst 2008; 4: 4: 300-8 More »
- Shestopalov IA, Chen JK "Chemical technologies for probing embryonic development." Chem Soc Rev 2008; 37: 7: 1294-307 More »
- Esengil H, Chang V, Mich JK, Chen JK "Small-molecule regulation of zebrafish gene expression." Nat Chem Biol 2007; More »
- Shestopalov IA, Sinha S, Chen JK "Light-controlled gene silencing in zebrafish embryos." Nat Chem Biol 2007; More »
12 publications: view full list
