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Jeffrey Axelrod
Email:
Phone:(650) 498-7543 Profile: http://med.stanford.edu/profiles/Jeffrey_Axelrod/
Alternate Contact: Academic Appointments
Appointment
Organization
Associate Professor
Member
Member
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Professional Education
Degree
Awarding Institution
Field of Study
Year of Graduation
M.D., Ph.D.
Washington University Sch of Med
Medicine and Molecular Biology
1991
Sc.B.
Brown University
Biochemistry
1981
Postdoctoral Advisees
Sarah Green,
Maja Matis,
Alison McGuigan,
Ying Peng,
Eszter Vladar
Web Site Links
Research/Lab website:
Axelrod Lab Homepage
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 this field in the past few years, our understanding of these signaling mechanisms and the accompanying cell biology are far from complete. We wish to continue exploring these important biological processes using a variety of approaches.
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 this field in the past few years, our understanding of these signaling mechanisms and the accompanying cell biology are far from complete. We wish to continue exploring these important biological processes using a variety of approaches.
Publications
- Chen WS, Antic D, Matis M, Logan CY, Povelones M, Anderson GA, Nusse R, Axelrod JD "Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling." Cell 2008; 133: 6: 1093-105 More »
- Amonlirdviman K, Khare NA, Tree DR, Chen WS, Axelrod JD, Tomlin CJ "Mathematical modeling of planar cell polarity to understand domineering nonautonomy." Science 2005; 307: 5708: 423-6 More »
- Ma D, Yang CH, McNeill H, Simon MA, Axelrod JD "Fidelity in planar cell polarity signalling." Nature 2003; 421: 6922: 543-7 More »
- Tree DR, Shulman JM, Rousset R, Scott MP, Gubb D, Axelrod JD "Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling." Cell 2002; 109: 3: 371-81 More »
- Yang CH, Axelrod JD, Simon MA "Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye." Cell 2002; 108: 5: 675-88 More »
33 publications: view full list
