Prof. Nancy Hynes (PhD)

Professor in Molecular Biology, Friedrich Miescher Institute for Biomedical Research

 

 

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ABOUT

Prof. Hynes started her career in 1975, after receiving a PhD in biochemistry at the University of Pittsburgh, USA. She then moved to Europe to complete post-doctoral appointments at the Max-Planck-Institute for Molecular Genetics, (Berlin, Germany) and the Swiss Cancer Institute (Lausanne, Switzerland).

In 1997, she received the title of “privatedozent” at the University of Basel, Switzerland, whereafter she was awarded a professorship in Molecular biology in 2003.

Prof. Hynes is the recipient of numerous honours such as the Swiss (2003) and German (2009) Cancer Prizes; the Dora Seif Prize from the Kantonsspital Basel (1995); and the Swiss Cancer League Robert-Wenner-Prize (1989).

Further, she has served on various editorial and scientific review boards, currently including the Pathophysiology and Endocrinology Advanced Grants Review Panel of the European Research Council (2007-2015); the Scientific Advisory Board member and board of Trustees member of the Max Delbruck Center for Molecular Medicine, Berlin, Germany (2011-2016); Komen Scholar Council Member, Susan G. Komen Race for the Cure (2010-2016); Member of the Charles Rodolphe Brupbacher Foundation (2015-current); President of the Scientific Committee of the Swiss Cancer League and the Swiss Cancer research Foundation (2015-current).

  • Breast cancer 90%
  • Estrogen receptor (ErbB2) 88%
  • Receptor tyrosine kinases (RTKs) 66%
  • Memo 40%
  • Ret receptor 33%
  • Metastasis and migration 30%
  • Fibroblast growth factor receptor (FGFR) 20%

RESEARCH INTERESTS

The Hynes laboratory has been studying molecular alterations in human breast cancer for over 25 years. One of our most important achievements was to be one of the first groups to discover ERBB2 gene amplification and receptor overexpression in primary breast tumors (Berger et al 1989). Following on this, we produced monoclonal antibodies targeting ErbB2ís ectodomain and used these to generate ErbB2 specific single-chain antibodies (scFv) and scFv-toxins that were recombinantly produced and shown to inhhibit in vivo growth of ErbB2-overexpressing tumors (Wels et al 1992).

We also developed a novel technique to study the roles of individual ErbB receptors by using scFvs to retain ErbB2 or EGFR in the endoplamic reticulum. Using this technology we made a number of conclusions about ErbB2ís role in the ErbB receptor family and in cancer: ErbB2 is the preferred partner for the other ligand-activated receptors (Graus-Porta et al 1997) and the ErbB2/ErbB3 heterodimer functions as a unit that controls proliferation of ErbB2-overexpressing breast cancer cells (Holbro et al 2003). Both papers continue to be highly cited.

We are also studying metastasis and migration. We identified novel ErbB2 interacting proteins; one of them, Memo (Marone et al 2004), was shown to be required for tumor cell dissemination in a metastatic model and its overexpression correlated with a higher risk of metastasis in breast cancer patients (MacDonald et al 2014). We have also identified other receptor tyrosine kinases (RTKs) in breast cancer with an important role in breast cancer. We have shown that the Ret receptor is overexpressed in sub-groups of tumors including ER+, ErbB2+ and triple negative (Boulay et al 2008; Gattelli et al 2013). Ongoing studies in the lab are aimed at understanding the specific role of Ret in breast cancer and the effects of blocking Ret activity on the tumor phenotype.

Members of the fibroblast growth factor receptor (FGFR) have also been implicated in different sub-types of breast cancer, including ER+ and a low percentage of basal-like tumors. The lab has been studying the role of FGFRs in signaling pathway activity and in tumor outgrowth by using FGFR selective kinase inhibitors (Dey et al 2010; Issa et al 2012).

RELEVANT PUBLICATIONS (of >230 total)

  1. A. Issa, J. W. Gill, M. R. Heideman, O. Sahin, S. Wiemann, J. H. Dey, N. E. Hynes. (2013) Combinatorial targeting of FGF and ErbB receptors blocks growth and metastatic spread of breast cancer models. Breast Cancer Res. 2013 Jan 23;15(1):R8.
  2. A. Gattelli, I. Nalvarte, A. Boulay, T.C. Roloff, M. Schreiber, N. Carragher, K. K. Macleod, M. Schlederer, S. Lienhard, L. Kenner, M. I. Torres-Arzayus, N. E. Hynes. (2013) Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells. EMBO Mol Med 5:1335-1350.
  3. S. Woehrle, C. Henninger, O. Bonny, A. Thuery, N. Beluch, N.E. Hynes, V. Guagnano, W.R. Sellers, F. Hofmann, M. Kneissel, D. Graus-Porta (2013) Pharmacological inhibition of FGFR signaling ameliorates FGF23-mediated hypophosphatemic rickets. J. Bone and Mineral Research 28: 899-911.
  4. B. Haenzi, O. Bonny, R. Masson, S. Lienhard, J.H. Dey, M. Kuro-o, N.E. Hynes (2014) Loss of Memo, a novel FGFR regulator, results in reduced lifespan. FASEB Journal 28: 327-336.
  5. S. Kondo, A. Bottos, J. C. Allegood, R. Masson, F. G. Maurer, C. Genoud, P. Kaeser, A. Huwiler, M. Murakami, S. Spiegel, N. E. Hynes (2014) Memo Has a Novel Role in S1P Signaling and Crucial for Vascular Development PLoS One. Apr 8;9(4):e94114. doi: 10.1371/journal.pone.0094114. eCollection 2014.
  6. G. MacDonald, I. Nalvarte, T. Smirnova, M. Vecchi, N. Aceto, A. Doelemeyer, A. Frei, S. Lienhard, J. Wyckoff, D. Hess, J. Seebacher, J. J. Keusch, H. Gut, D. Salaun, G. Mazzarol, D. Disalvatore, M. Bentires-Alj, P.P. Di Fiore, A. Badache, N. E. Hynes (2014) Memo is a copper-dependent redox protein with an essential role in migration and metastasis. Science Signaling 9 (329):ra56.
  7. F. Chiovaro, E. Martina, A. Bottos, A. Scherberich, N.E. Hynes, R. Chiquet-Ehrismann (2015) Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells. Int. J. Cancer, in press.
  8. N.E.Hynes, M.R. Heideman (2013) Axl/epidermal growth factor receptor (EGFR) complexes in breast cancer- culprits for resistance to EGFR inhibitors? Breast Cancer Res 15:315
  9. N.E.Hynes, P.W. Ingham, W. A. Lim, C. J. Marshall, J. Massague, T. Pawson (2013) Signaling change: signal transduction through the decades. Nature Rev Mol Cell Biol 14:393-398.
  10. A. W. Burgess, Y. I. Henis, N.E. Hynes, T. Jovin, A. Levitzki, R. Pinkas-Kramarski, Y. Yarden (2014) EGF receptor family: twisting targets for improved cancer therapies. Growth Factors Apr;32 (2):74-81.
  11. A. Bottos, N.E. Hynes (2014) Staying together on the road to metastasis. Nature 514:309-310.