Photo of Gerburg Wulf,  MD, PhD

Gerburg Wulf, MD, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-1910
Fax: (617) 667-0610

Gerburg Wulf, MD, PhD

Beth Israel Deaconess Medical Center


  • Associate Professor, Medicine, Harvard Medical School
  • Active Staff, Hematology/Oncology, Beth Israel Deaconess Medical Center


Research Abstract

Much cancer research focuses on the molecular mechanisms of neoplastic transformation with the hope that understanding the mechanisms of carcinogenesis will provide keys to the development of new therapeutic avenues. A major therapeutic target is the cell cycle machinery of cancer cells. My work in the last several years has focused on the mechanisms that link cell cycle control with oncogenesis, specifically on the role of the prolyl isomerase Pin1 in breast cancer.

Pin1 regulates the function of a subset of phosphoproteins, presumably by binding and isomerizing their phosphorylated S/T-P motifs. Inhibition of Pin1 causes growth arrest in tumor cells and contributes to neuronal death in Alzheimer's disease. We found that Pin1 is overexpressed in human breast cancer cell lines and 75% of breast cancer tissues, and that its levels correlate with the nuclear grade of the tumors and their cyclin D1 protein and mRNA expression. Pin1 mRNA levels were elevated in those tumors examined suggesting that Pin1 expression is at least in part regulated on the transcriptional level. Induced expression of Pin1 elevates cellular cyclin D1 levels and activates its promoter through the AP-1 site. Importantly, Pin1 binds to phosphorylated c-Jun and dramatically increases its ability to activate the cyclin D1 promoter in cooperation either with oncogenic Ha-Ras or activated JNK; these effects depend on phosphorylation of c-Jun on S63/73-P and the isomerase activity of Pin1. Given the crucial roles of Ras signaling and cyclin D1 overexpression in oncogenesis, my results suggest that overexpression of Pin1 may promote tumor growth. To examine this hypothesis, I am currently analyzing the significance of Pin1 for mammary tumorigenesis in a mouse model.


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  • Luo ML, Gong C, Chen CH, Hu H, Huang P, Zheng M, Yao Y, Wei S, Wulf G, Lieberman J, Zhou XZ, Song E, Lu KP. The Rab2A GTPase Promotes Breast Cancer Stem Cells and Tumorigenesis via Erk Signaling Activation. Cell Rep 2015. PubMed
  • Luo ML, Gong C, Chen CH, Lee DY, Hu H, Huang P, Yao Y, Guo W, Reinhardt F, Wulf G, Lieberman J, Zhou XZ, Song E, Lu KP. Prolyl Isomerase Pin1 Acts Downstream of miR200c to Promote Cancer Stem-like Cell Traits in Breast Cancer. Cancer Res 2014. PubMed
  • Emerling BM, Hurov JB, Poulogiannis G, Tsukazawa KS, Choo-Wing R, Wulf GM, Bell EL, Shim HS, Lamia KA, Rameh LE, Bellinger G, Sasaki AT, Asara JM, Yuan X, Bullock A, Denicola GM, Song J, Brown V, Signoretti S, Cantley LC. Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-null tumors. Cell 2013; 155:844-57. PubMed
  • Israelsen WJ, Dayton TL, Davidson SM, Fiske BP, Hosios AM, Bellinger G, Li J, Yu Y, Sasaki M, Horner JW, Burga LN, Xie J, Jurczak MJ, DePinho RA, Clish CB, Jacks T, Kibbey RG, Wulf GM, Di Vizio D, Mills GB, Cantley LC, Vander Heiden MG. PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells. Cell 2013; 155:397-409. PubMed
  • Juvekar A, Burga LN, Hu H, Lunsford EP, Ibrahim YH, Balmañà J, Rajendran A, Papa A, Spencer K, Lyssiotis CA, Nardella C, Pandolfi PP, Baselga J, Scully R, Asara JM, Cantley LC, Wulf GM. Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer. 2012; 2:1048-63. PubMed
  • Burga LN, Hu H, Juvekar A, Tung NM, Troyan SL, Hofstatter EW, Wulf GM. Loss of BRCA1 leads to an increase in epidermal growth factor receptor expression in mammary epithelial cells, and epidermal growth factor receptor-inhibition prevents estrogen receptor-negative cancers in BRCA1-mutant mice. Breast Cancer Res 2011; 13:R30. PubMed
  • Yuan TL, Wulf G, Burga L, Cantley LC. Cell-to-cell variability in PI3K protein level regulates PI3K-AKT pathway activity in cell populations. Curr Biol 2011; 21:173-83. PubMed
  • Dohm A, Hasenkamp J, Bertsch HP, Maas JH, Truemper L, Wulf G. Progression of a CD4+/CD56+ blastic plasmacytoid DC neoplasm after initiation of extracorporeal photopheresis in an allogeneic transplant recipient. Bone Marrow Transplant 2010. PubMed
  • Ryo A,Wulf G,Lee TH,Lu KP. Pinning down HER2-ER crosstalk in SMRT regulation. Trends Biochem Sci 2009; 34:162-5. PubMed
  • Burga LN,Tung NM,Troyan SL,Bostina M,Konstantinopoulos PA,Fountzilas H,Spentzos D,Miron A,Yassin YA,Lee BT,Wulf GM. Altered proliferation and differentiation properties of primary mammary epithelial cells from BRCA1 mutation carriers. Cancer Res 2009; 69:1273-8. PubMed
  • Lam PB,Burga LN,Wu BP,Hofstatter EW,Lu KP,Wulf GM. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability. Mol Cancer 2008; 7:91. PubMed
  • Lu KP, Suizu F, Zhou XZ, Finn G, Lam P, Wulf G. Targeting carcinogenesis: a role for the prolyl isomerase Pin1? Mol Carcinog 2006; 45:397-402. PubMed
  • Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 2006; 440:528-34. PubMed