James K. Chen
Academic Appointments
- Associate Professor, Chemical and Systems Biology
- Member, Child Health Research Institute
- Member, Stanford Cancer Institute
- Member, Bio-X
- Associate Professor, Developmental Biology
- Associate Professor (By courtesy), Natural Sciences Cluster - Chemistry Department
Key Documents
Contact Information
- Academic Offices
Personal Information Email Tel (650) 725-3582Alternate Contact Stuart Jeung Administrative Assistant Email Tel Work (650) 736-2999
Professional Overview
Administrative Appointments
- Executive Committee Member, Stanford University Chemical Biology Institute (2012 - present)
- Steering Committee Member, Stanford University School of Medicine Faculty Senate (2012 - present)
- Departmental Representative, Stanford Biosciences Committee on Graduate Admissions and Policy (2012 - present)
- Director, Advisory Committee for the Scholarly Concentrations Program in the Molecular Basis of Medicine (2012 - present)
- Alternate Member, Stanford University Administrative Panel on Laboratory Animal Care (2012 - present)
- Departmental Representative, Stanford University School of Medicine Faculty Senate (2009 - present)
Honors and Awards
- Nature SciCafe Award for Outstanding Research Achievement, Nature Biotechnology and Nature Medicine (2009)
- NIH Director's Pioneer Award, NIH (2008-2013)
- American Cancer Society Research Scholar Award, American Cancer Society (2008-2011)
- Brain Tumor Society Award, Brain Tumor Society/Rachel Molly Markoff Foundation (2006-2008)
- Astellas USA Foundation Award, Astella USA Foundation (2005-2006)
- Terman Fellow, Stanford University (2005-2008)
Professional Education
| A.B.: | Harvard College, Chemistry (1991) |
| Ph.D.: | Harvard University, Chemistry and Chemical Biology (1999) |
| Postdoctoral Fellow: | Johns Hopkins School of Medicine, Molecular Biology and Genetics (2003) |
Postdoctoral Advisees
John Crapster, Lukasz Kowalik, Karen Mruk, Jun Ni, Alison Ondrus, Xiaohu Ouyang, Sayumi Yamazoe
Graduate & Fellowship Program Affiliations
Internet Links
Industry Relationships
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Scientific Focus
Current Research Interests
The Chen laboratory integrates synthetic chemistry and developmental biology to interrogate the molecular mechanisms that control embryonic patterning, tissue regeneration, and oncogenesis. Our research group is currently focused on three major areas: the identification of small-molecule and genetic regulators of Hedgehog signaling, the development of chemical technologies for perturbing and observing the molecular programs of embryonic patterning and tumorigenesis, and the study of tissue regeneration using zebrafish as a model organism.
Our interest in the Hedgehog pathway arises from its critical role in the patterning of multiple tissues such as the neural tube, craniofacial structures, 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. Since the cellular events that transduce the Hedgehog signal from the cell surface to the nucleus are not well understood, we are pursuing genetic and small-molecule screens for new Hedgehog pathway modulators with novel modes of action. These studies will not only provide insights into the basic mechanisms of Hedgehog signal transduction but also provide chemical leads for the development of next-generation chemotherapies and reveal new druggable targets within this tumor-promoting pathway.
Our laboratory is also investigating how Hedgehog signaling and other developmental pathways regulate tissue formation and regeneration in vertebrates. We use the zebrafish as a model organism for these studies, exploiting its rapid ex utero development and amenability to real-time imaging. As part of these efforts, we have developed new strategies for activating and silencing gene expression in zebrafish embryos with unprecedented spatial and temporal precision. These methods utilize chemical probes developed by our research group, including caged reagents that allow light-controlled gene silencing in whole organisms. In conjunction with conventional genetic approaches, these chemical technologies will help us elucidate the genetic programs that control vertebrate development and physiology.
Understanding the molecular mechanisms that underlie tissue regeneration is an emerging interest in our laboratory. The zebrafish is an ideal system for studying these processes, since it has the unique ability to regenerate its heart, retina, spinal cord, fins, and other body parts. Our research group is working with Michael Longaker's laboratory to decipher the molecular and cellular events associated with larval tail regeneration, and we have identified several genes that are upregulated or downregulated in posterior cells after the tail is amputated. We are now using an interdisciplinary approach to determine the roles of these genes in the regenerative process.
Publications
- Functional inhibition of UQCRB suppresses angiogenesis in zebrafish. Biochem Biophys Res Commun. 2013; (4): 396-400
- Cyclic caged morpholinos: conformationally gated probes of embryonic gene function. Angew Chem Int Ed Engl. 2012; (28): 6908-11
- Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein. Nature. 2012; (7392): 125-9
- Spatiotemporal resolution of the Ntla transcriptome in axial mesoderm development. Nat Chem Biol. 2012; (3): 270-6
- The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature. 2012; (7392): 115-9
- A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med. 2011; (11): 1504-8
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