Picture of FEKETE

DONNA FEKETE

Professor
The John and Donna Krenicki Directorship of Integrative Neuroscience
LILY 2-224
Phone: 765-496-3058

My laboratory is interested in the molecular basis of inner ear development, including morphogenesis, cell fate specification, axon guidance and sensory cell differentiation.  The vertebrate inner ear houses the sensory organs for hearing and balance.  Sound reaches these sensory cells through a series of conductive elements that comprise the outer and middle ears.  Components of the inner ear include a fluid-filled epithelial sac and resident neuronal ganglion cells, all surrounded by loose mesenchyme and bone.  These tissues originate on the side of the head, either from the ectodermally-derived otic placode, the neural crest, the presomitic mesoderm or the endoderm.  Because of these varied embryonic origins, ear malformations often occur in the context of developmental problems in other organs or tissues, leading to syndromic forms of deafness. Over 400 forms of syndromic deafness have been characterized in humans.  In other cases, deafness is the only known defect, and in those cases the responsible genes are often associated with some specialized function of inner ear sensory cells.  In addition to hearing loss, genetic defects in ear formation or function can also lead to balance disorders. At present, there are hundreds of genes expressed in the embryonic ear that need to be functionally analyzed for their role in ear development and function.

Our lab primarily uses chicken and mouse as animal models in our research.  We have a specific interest in studying the Wnt signaling pathway and the roles of microRNAs, a small class of non-coding RNAs that serve to regulate gene expression. Ongoing collaborations with other research labs inform our choice of candidate genes to explore and manipulate.  We use gene transfer techniques including infection with viral vectors or electroporation of plasmid DNA (in chicken embryos) to manipulate the levels of candidate molecules during development. Both overexpression and knockdown approaches can be informative in revealing the normal function of a candidate gene. Our hope is that the outcome of our research endeavors will lead to the design of new therapeutic treatments for deafness and balance disorders. For example, we have designed a study to use viral gene transfer to deliver microRNAs into the drug-damaged mouse cochlea to attempt to induce hair cell regeneration and rescue hearing loss.

We are collaborating with the Kuhn lab (Purdue) to study the neural tropism of Zika virus in the developing neural tube and inner ear.  We are exploring whether Zika virus displays preferential infection of neural progenitors in specific regions of the brain or inner ear, with the goal of gaining a better understanding of how infection leads to developmental defects in the nervous system and hearing loss.

Current Lab Personnel:

Lab Manager: Deb Biesemeier

Research Assistant:  Adam Lorch

Postdoctoral Fellow:  Vidhya Munnamalai

Graduate Students:  Katie Scott, Ankita Thawani

Undergraduate Students: Bella Yue, Hannah Reygaerts, Nabilah Sammundin, Nick Charles-Romanov Heppner-Lundin, Alexandra Fister, Julie Lee

 

 

 

The movie shows how the embryonic chicken inner ear develops from a simple round vesicle into the complex labyrinth that includes semicircular canals on top and the sickle-shaped cochlear duct on the bottom. The sequence begins on the third day after the egg is laid and ends on the 16th day. The chick hatches during the 21st day. The ears were fixed, dehydrated, cleared, and injected with white latex paint; digital images were taken through a dissection microscope and morphing software was applied to visualize structural changes over time. The images and movie are courtesy of J.P. Bissonnette and Laurie Iten, respectively.

Education

B.S., Biological Sciences, summa cum laude, University of Vermont, 1979

Ph.D., Anatomy, Harvard University, 1984

Postdoctoral Fellow, MRC Cell Biophysics Unit and Ludwig Institute for Cancer Research, London, England

Postdoctoral Fellow, Department of Genetics, Harvard Medical School

Awards

Basil O'Connor Scholar, March of Dimes Birth Defects Foundation (1993-1996)

Clare Booth Luce Professorship, Henry Luce Foundation (1993-1998)

Marcus Singer Award, Midwest Regional Developmental Biology Meeting (2001)

University Faculty Scholar, Purdue University (2005-2010)

AAAS Fellow (2009)

J. Alfred and Martha Chiscon Undergraduate Teaching Award, Department of Biological Sciences, Purdue University (2011)

Faculty of 1000 (2011)

Leadership Award, College of Science, Purdue University (2011, 2015)

Grants

NIH RO1DC02756, Development studies of the inner ear, 03/01/2014-02/28/2019

NIH R21DC016376, Gene networks in cochlear patterning, 07/01/2017-06/30/2020 (PI: Munnamalai)

NIH F31DC015946, Molecular regulators of innervation and patterning across the developing cochlea, 08/12/2016-8/11/2018 (PI:  Scott)

NIH R21DC016732, Zika virus cell tropism and pathogenesis in the developing inner ear, 09/21/2017-08/31/2019

Other Activities

 

 Editorial Boards (current and past)

  • Developmental Biology
  • Developmental Neurobiology
  • Development
  • JARO
  • Journal of Neuroscience
  • Developmental Dynamics

Other Professional Activities

  • John & Donna Krenicki Director, Purdue Institute for Integrative Neuroscience
  • Member, Purdue Integrative Neuroscience Training Group, PULSe Graduate Program
  • Member, Society for Neuroscience
  • Member, Society for Developmental Biology
  • Member, Association for Research in Otolaryngology
  • Member, American Association for the Advancement of Science
  • Member, Purdue Cancer Center
  • Member, Purdue Institute for Inflammation, Immunology & Infectious Disease

Recent Publications

  • Munnamalai, V., U. J. Sienkneckt, R. K. Duncan, M. K. Scott, A. Thawani, K. N. Fantetti, N. A. Atallah, D. J. Biesemeier, K. H. Song, K. Luethy, E.Traub and D.M. Fekete. 2017. Wnt9a can influence cell fates and neural connectivity across the radial axis of the chicken cochlea. Journal of Neuroscience. doi.org/10.1523/JNEUROSCI. 1554-17.2017. published online 14 August 2017.

  • Nishitani, A. M., S. Ohta, A. R. Yunga, M. I. Gordon, T. del Rio, V. E. Abraira, G. C. Schoenwolf, D. M. Fekete, L. V. Goodrich. Conserved yet divergent functions for Netrin-1 in chick and murine semicircular canal morphogenesis. Development doi:10.1242/dev.144519, posted online August 29, 2017.
  • Groves, A.K. and D. M. Fekete. 2017. New directions in cochlear development.  Springer Handbook Series: The Cochlea (G. Manley, R.R. Fay and A. N. Popper, eds.), New York:  Springer.

  • Lutz, G., I. Jurak, E. T. Kim, J. Y. Kim, M. Hackenberg, A. Leader, M. L. Stoller, D. M. Fekete, M. D. Weitzman, D. M. Coen, A. C. Wilson. 2017. Viral ubiquitin ligase stimulates selective host microRNA expression by targeting ZEB transcriptional repressors. Animal Viruses, 9, 10; doi:10.3390/v9080210. Published online 7 August 2017

  • Munnamalai, V.  and D.M. Fekete, 2016. Notch-Wnt-Bmp crosstalk regulates radial patterning in the mouse cochlea in a spatiotemporal manner. Development, 143:4003-4015; doi: 10.1242/dev.139469.

  • Fekete, D.M. 2016. Development of the ear. In: Inborn Errors of Development, (C.J. Epstein, R.P. Erickson and W. Wynshaw-Boris, eds.) Oxford University Press, Third Edition.

  • Munnamalai, V. and D.M. Fekete, 2016. Organotypic culture of the mouse cochlea from embryonic day 12 to the neonate. Methods Molecular Biology, Vol. 1427, Bernd Sokolowski (Ed.): Auditory and Vestibular Research, Springer, pp. 293-303.

  • Stoller, M.L. and D.M. Fekete 2016. Tol2-mediated delivery of miRNAs to the chicken otocyst using plasmid electroporation.  Methods Molecular Biology, Vol. 1427, Bernd Sokolowski (Ed.): Auditory and Vestibular Research, Springer, pp. 27-42.
  • Zhang, K.D. , M.L. Stoller and D.M. Fekete. 2015. Expression and misexpression of the miR-183 family in the developing hearing organ of the chicken.  PLoS ONE. 10.1371/journal.pone.0132796.

  • Battisti A. C., K.N. Fantetti, B.A. Moyers and D.M. Fekete, 2014. A subset of chicken statoacoustic ganglion neurites are repelled by Slit1 and Slit2.  Hearing Research 310: 1-12.

  • Jiang, H., L. Wang, K. T. Beier, C. L. Cepko, D.M. Fekete and J. V. Brigande. 2013. Lineage analysis of the late otocyst stage mouse inner ear by transuterine microinjection of a retroviral vector encoding alkaline phosphatase and an oligonucleotide library.  PLOS ONE 2013 Jul 25;8(7):e69314. doi: 10.1371/journal.pone.0069314.

  • Stoller, M.L., H. C. Chang and D. M. Fekete. 2013. Bicistronic gene transfeer tools for delivery of miRNAs and protein coding sequences.   International Journal of Molecular Science, 14(9):18239-55. doi: 10.3390/ijms140918239.

  • Groves, A.K., K.D. Zhang and D.M. Fekete, 2013. The genetics of hair cell development and regeneration.  Annual Reviews of Neuroscience, 36: 361-381. 

  • Munnamalai, V. and D.M. Fekete, 2013. Wnt signaling during cochlear development.  Seminars in Cell and Developmental Biology. 14: 480-489.

  • Groves, A.K. and D.M. Fekete. 2012.  Shaping sound in space: the regulation of inner ear patterning.  Development,  Development 139: 245-257.

  • Fantetti, K.N. and D.M. Fekete. 2011.  Members of the BMP, Shh and FGF morphogen families promote statoacoustic ganglion neurite outgrowth and neuron survival in vitro. Developmental Neurobiology, 72: 1213-1228.

  • Fantetti, K.N. and D.M. Fekete. 2011. Dissection and culture of chick statoacoustic ganglion and spinal cord explants in collagen gels for neurite outgrowth assays.  JoVE (Journal of Visualized Experiments), (58), e3600, DOI: 10.3791/3600 (2011). .

  • Fantetti, K.N, Y. Zou and D.M. Fekete. 2011.  Wnts and Wnt inhbitors do not influence axon outgrowth from chicken statoacoustic ganglion neurons.  Hearing Research, 278: 86-95.

  • Sienknecht, U.J., B.K. Anderson, R.M. Parodi, K.N. Fantetti and D.M. Fekete. 2011. Non-cell-autonomous planar cell polarity propagation in the auditory sensory epithelium of vertebrates.  Developmental Biology, 352:27-39.

  • Liang, H., D. M. Fekete and O. Andrisani.  2011. CtBP2 down-regulation during neural crest specification induces expression of Mitf and REST, resulting in melanocyte differentiation and sympathoadrenal lineage suppression. Molecular and Cellular Biology, 31:955-970.

  • Kilpatrick, L.A., Q. Li, J. Yang, J. C. Goddard, D. M. Fekete, H. Lang. 2011. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear, Gene Therapy. advance online publication 6 January 2011; doi: 10.1038/gt.2010.175

  • Li, H., W. Kloosterman and D.M. Fekete. 2010. MicroRNA-183 family members regulate sensorineural fates in the inner ear. Journal of Neuroscience. 30: 3254-3263.

  • Abraira, V.E., T. Satoh, D.M. Fekete and L. V. Goodrich. 2010. Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis. PLoS ONE, 01 Feb 2010 | 10.1371/journal.pone.0008981.

  • Li, H. and D.M.Fekete. 2010. MicroRNAs in hair cell development and deafness. Current Opinion in Otolaryngology and Head and Neck Surgery. 18:459-465.

  • Friedman, L.M., A.A. Dror, E. Mor, T. Tenne, G. Toren, T. Satoh, D.J. Biesemeier, N. Shomron, D.M. Fekete, E. Hornstein and K.B. Avraham. 2009. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. PNAS, 106:7915-7920.

  • Sienknecht, U.J. and D.M. Fekete. 2009. Mapping of Wnt, Frizzled and Wnt inhibitor gene expression domains in the avian otic primordium. Journal of Comparative Neurology, 517: 751-764.

  • Satoh, T. and D. M. Fekete 2008. Lineage analysis of inner ear cells using genomic tags for clonal identification. In: Auditory and Vestibular Research: Methods and Protocols (B. Sokalowski, ed.). Methods in Molecular Biology, 493: 47-63.

  • Fekete, D.M. Development of the ear. 2008. In: Inborn Errors of Development, (C.J. Epstein, R.P. Erickson and W. Wynshaw-Boris, eds.) Oxford University Press, Second Edition.

  • Fekete, D.M. and U.J. Sienknecht. 2007. Inner ear. In: Sally A Moody (ed.), Principles of Developmental Genetics, Elsevier Press, pp. 631-655. 


Professional Faculty Research

(Neuroscience and Developmental Biology)  Development of the inner ear; Zika virus infection of the brain and inner ear

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