Roeland Nusse

Administrative Appointments

• Chair, Developmental Biology (2007 - 2012)

Honors and Awards

• Member, US National Academy of Sciences (2010)
• Member, American Academy of Arts and Sciences (2001)
• Member, Royal Dutch Academy of Sciences (1997)
• Member, European Molecular Biology Organization (1988)

Postdoctoral Advisees

Shukry Habib,  Hinako Takase

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Developmental Biology

Internet Links

• Nusse Lab Home Page

Industry Relationships

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Current Research Interests

During the developmental of an animal, cells become progressively and stepwise committed to specialized fates. Many of the decisions that cells make during embryogenesis are regulated by a relatively small number of signaling factors, including the Wnt, BMP and Hedgehog proteins. During the regeneration and renewal of adult tissue, the same signals control how stem cells divide. Unrestrained Wnt signaling, after mutations in Wnt signaling components, is implicated in cancer, including human colon cancer.
Our laboratory has a long-standing interest in the activity of Wnt proteins during embryogenesis and other processes. One of our major recent contributions to the field has been to develop methods to purify Wnt proteins in an active form. With the purified proteins, we could establish that Wnt proteins are modified by fatty acids. We have also used the purified Wnt proteins to manipulate the behavior of stem cells in culture, in particular neural stem cells. We have evidence that those stem cells respond to Wnt signals in vivo, in structures called niches.
We are also interested in Wnt signaling during the repair of damaged tissue. This follows the evidence that the same pathways that control growth of embryonic cells also govern regeneration of adult tissue. In the lung, several mutant phenotypes have revealed that the Wnt pathway is required for lung development, but its function in adult tissues is not well understood. We have examined the activation of Wnt signaling in adult lungs using different Wnt reporter mice, in which signaling can be visualized in vivo. These reporter lines reveal Wnt signaling in Clara cells, suggesting that Wnts may play a role in Clara cell formation or maintenance.

Publications

• Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. Mulligan KA, Fuerer C, Ching W, Fish M, Willert K, Nusse R. Proc Natl Acad Sci U S A. 2012; 109 (2): 370-7
• Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. ten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A, Eroglu E, Siu RK, Nusse R. Nat Cell Biol. 2011; 13 (9): 1070-5
• Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Zeng YA, Nusse R. Cell Stem Cell. 2010; 6 (6): 568-77
• Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. Mikels AJ, Nusse R. PLoS Biol. 2006; 4 (4): e115
• Wnt proteins are lipid-modified and can act as stem cell growth factors. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, Nusse R. Nature. 2003; 423 (6938): 448-52