Jeffrey Axelrod
Academic Appointments
- Associate Professor, Pathology
- Member, Bio-X
- Member, Cancer Center
Contact Information
- Academic
Offices
Personal Information Email Tel (650) 498-7543 Tel (650) 498-7687Administrative Contact Elaine Ruiz Administrative Assistant Email Tel Work 723-7042
Professional Snapshot
Professional Education
| M.D., Ph.D.: | Washington University Sch of Med, Medicine and Molecular Biology (1991) |
| Sc.B.: | Brown University, Biochemistry (1981) |
Postdoctoral Advisees
Graduate & Fellowship Program Affiliations
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Scientific Focus
Current Research Interests
Cell growth, differentiation, and generation of cellular asymmetry underlie most processes in development, and when they are perturbed, contribute to a broad range of disease states. We combine genetic, molecular, cell biological and computational approaches in Drosophila and other model systems to address these problems. Our lab studies signaling processes governing the acquisition of a cellular asymmetry referred to as Planar Cell Polarity (PCP), which orients the cytoskeleton of epithelial cells within a plane orthogonal to their apical-basal axes. We also study a specific growth and differentiation signal mediated by the Wnt family of ligands. These signal transduction pathways are intimately related, through their requirement for a shared receptor, Frizzled and some downstream signal transducers, before diverging to produce different cellular responses. We would like to understand the mechanism by which PCP signaling senses global direction, generates cellular asymmetry in the proper orientation, and produces an asymmetric cellular readout. We would also like to understand the critical process of regulating Wnt mediated growth and differentiation, which, when unchecked, can lead to oncogenesis.
Using the Drosophila model system, we have demonstrated that cellular asymmetry in PCP results from the asymmetric localization of PCP signaling components, and have shown that this asymmetry is generated through the function of a novel intercellular signaling loop. Furthermore, we have identified a set of signaling molecules that provides a global cue that orients Frizzled signaling to the axes of the appendage or body, and have shown that the overall design of the system produces an exceptionally high-fidelity response. We have found that the PCP and oncogenic Wnt pathways share regulatory components, and that some of these shared components work in a complex that has tumor suppressor properties in the oncogenic Wnt pathway. Despite the considerable progress in...
Publications
- Cell packing influences planar cell polarity signaling. Proc Natl Acad Sci U S A. 2008; (48): 18800-5
- Hedgehog and Wingless stabilize but do not induce cell fate during Drosophila dorsal embryonic epidermal patterning. Development. 2008; (16): 2767-75
- Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell. 2008; (6): 1093-105
- Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science. 2005; (5708): 423-6
- Fidelity in planar cell polarity signalling. Nature. 2003; (6922): 543-7
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