PROFESSIONAL EXPERIENCE:

• Post-doctoral Fellow, Rockefeller University, Laboratory of Molecular Biology (1989-1996) 
• Research Fellow, Ernst Boehringer Institute, Boehringer Ingleheim Ges. M.B.H., Vienna,
  Austria (1987-1989)

EDUCATION:

• Columbia University, New York, NY, Ph.D. (1989) 
• Hampshire College, Amherst, MA, BA (1975)

RESEARCH:

1. Cell cycle regulation during the development and regeneration of the inner ear.
   Coordinating cell proliferation, growth and differentiation is crucial for the development of animal form. This project investigates the biochemical machinery responsible for this coordination.
   Including projects on:
   • Regulation of cyclin-dependent kinases and their inhibitors in development.
   • Role of proneural and neurogenic genes in cell patterning, differentiation, and cell cycle control.
   • Reprogramming gene expression during regeneration.

2. Stem cells and progenitors in the developing inner ear.
   This project involves the prospective identification, purification and growth in vitro of hair cell precursors.  The goal is the identification and molecular characterization of progenitor cells that are able to divide and differentiate into the sensory and non-sensory cells of the auditory and vestibular epithelium. In the future, manipulation of these cells may offer an alternative to hearing aids and cochlear implants for the treatment of hearing loss.

3. Establishment and maintenance of the postmitotic state.
   The focus of this project is on the molecular mechanisms that underlie the permanently postmitotic state of terminally differentiated cells. We are interested in the control systems needed to maintain the non-dividing state, and the mechanisms that link environmental stress to failure of these control systems, DNA damage, and cell death.

SELECTED PUBLICATIONS:

• Doetzlhofer, A., Basch, M. Gessler, M., Groves, A. K., and Segil, N. (2009).  Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti.  Developmental Cell 16: 58-69.

• Jayasena, C. S., Ohyama, T., Segil, N., Groves, A. K. (2008).  Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development 135: 2251-2261.

• Raft, S., Koundakjian, E. J., Quinones, H., Jayasena, S. C., Goodrich, L. V., Johnson, J. E., Segil, N. and Groves, A. (2007).  Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development, 134:4405-4415.

• Laine, H., Doetzlhofer, A., Mantela, J., Ylikoski, J., Laiho, M., Roussel, M.F., Segil, N., and Pirvola, U. (2007)  p19^Ink4d and p21^Cip1 collaborate to maintain the postmitotic state of auditory hair cells, their co-deletion leading to DNA damage and p53-mediated apoptosis. Journal of Neuroscience 27(6):1434-1444.

• White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K., and Segil, N. (2006). Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441:984-987. -PubMed

• Lee, Y. -S. Liu, F., and Segil, N (2006). Transcriptional Regulation of p27Kip1 Directs a Morphogenetic Wave of Cell Cycle Exit in the Developing Organ of Corti. Development. 2006 Jun 21; [Epub ahead of print]. -PubMed

• Doetzlhofer, A., White, P.M., Johnson, J.E., Segil, N., and Groves, A.K. (2004). In vitro growth and differentiation of mammalian sensory hair cell progenitors: a requirement for EGF and periotic mesenchyme. Developmental Biology, 272:432-447. -PubMed

• Chen, P., Zindy, F., Abdala, C., Liu, F., Li, X., Roussel, M.F., and Segil, N. (2003). Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nature Cell Biology 5:422-426 -PubMed

• Chen, P. Johnson, J.E.. Zoghbi, H.Y., and Segil, N., (2002). The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129, 2495-2505 -PubMed

• Chen P, Segil N. (1999) p27Kip1 links cell proliferation to morphogenesis in the developing organ of Corti. Development 126:1581-1590. -PubMed

• Segil N, Guermah M, Hoffmann A, Roeder RG, Heintz N. (1996) Mitotic regulation of TFIID: Inhibition of activator-dependent transcription and changes in sub-cellular localization. Genes and Development 10:2389-2400. -PubMed

• Segil N, Roberts SB, Heintz N. (1991) Mitotic phosphorylation of the Oct-1 POU-homeodomain and the regulation of Oct-1 DNA binding activity. Science 254:1814-1816. -Pubmed

• White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K., and Segil, N. (2006). Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441:984-987. -PubMed