Dr. DONNA FEKETE

Professor
765-496-3058
LILY 2-224
dfekete@purdue.edu

Associated website(s):

PROFESSIONAL FACULTY RESEARCH

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

BIO

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.

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 and Honors

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)

John & Donna Krenicki Directorship in Integrative Neuroscience (2017-2018)

College of Science Research Award, Purdue University (2018)

Grants

NIH RO1DC02756, Development studies of the inner ear, 03/01/2014-present

NIH T32DC016853, Interdisciplinary training in auditory neuroscience, 07/01/2018-06/30/2023

Other Activities

Editorial Boards (current and past)

Developmental Biology
Developmental Neurobiology
Development
JARO
Journal of Neuroscience
Developmental Dynamics

Other Professional Activities

Communications Director, Council Member, Association for Research in Otolaryngology
Board of Scientific Counselors, National Institute for Deafness & Communication Disorders, NIH

Recent Publications

• Munnamalai, V., N.H. Sammudin, C.A. Young, A. Thawani, R.J. Kuhn and D.M. Fekete. 2021. Embryonic and neonatal mouse cochleae are susceptible to Zika virus infection. Viruses 13, 1823. https://doi.org/10.3390/v13091823.
• Thawani, A., N.H. Sammundin, H.S. Reygaerts, A.N. Wozniak, V. Munnamalai, R.J. Kuhn, D.M. Fekete, 2020. Zika virus can directly infect and damage the auditory and vestibular components of the embryonic chicken inner ear. Developmental Dynamics 249: 867-883. https://doi.org/10.1002/dvdy.176.
• Scott, M.K., J. Yue, D.J. Biesemeier, J.W. Lee and D.M. Fekete . Expression of class III semaphorins and their receptors in the developing chicken (Gallus gallus) inner ear. Journal of Comparative Neurology, Journal of Comparative Neurology 527: 1196-1209.
• Hsieh, W.-C., S. Ramadesikan, D. Fekete, R.C. Aguilar. 2018. Kidney differentiated cells derived from Lowe Syndrome patient’s iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex. PlosOne, 13: e1092635. DOI: 10.1371/journal.pone.0192635.
• Thawani, A., D. Sirohi, R.J. Kuhn and D.M. Fekete . 2018. Zika virus can strongly infect and disrupt secondary organizers in the ventricular zone of the embryonic chicken brain. Cell Reports. 23: 692-700.
• 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. 37:8975-8988.
• Munnamalai, V. and D.M. Fekete . 2017. Building the human inner ear in an organoid. Nature Biotechnology. 35:518-520.
• Nishitani, A. M., S. Ohta, A. R. Yung a , M. I. Gordon, T. del Rio, V. E. Abraira, G. C. Schoenwolf, D. M. Fekete , L. V. Goodrich. 2017. Distinct functions for Netrin-1 in chick and murine semicircular canal morphogenesis. Development 144:3349-3360.
• 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.
• 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.01327

Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/si... ection=descending