Alain Dabdoub

Dr. Alain Dabdoub completed his PhD at the University of Maryland in electrophysiology studying the phototransduction signaling pathway.

His interest in signal transduction continued as a postdoc and he focused on elucidating the developmental pathways in the mammalian inner ear at the National Institute on Deafness and Other Communication Disorders at the NIH.

In 2008 Dr. Daboub accepted a faculty position at the University of California San Diego and in 2012 was recruited to the University of Toronto.

He is the research director of the Hearing Regeneration Initiative at the Sunnybrook Research Institute where his laboratory is located. 

His research focuses on development and regeneration of the mammalian inner ear.

Research Synopsis

Hearing loss is the most common sensory disability and affects 0.3% of newborns, 5% of people under age 45, and 50% by age 70, impacting 600 million people worldwide (World Health Organization). 

According to The Canadian Association for the Deaf there are 3.5 million profoundly deaf or hard-of-hearing individuals in Canada and the prevalence of hearing loss is expected to double as the population ages over the next 25 years.

Since there is no biological solution for hearing loss, we focus on discovery science and pursue translational research for the amelioration of hearing impairment.

I center my research on discovering and elucidating the molecular signaling pathways and transcription factors responsible for neurodevelopment and regeneration of the mammalian cochlea, the hearing organ.  

In addition to its basic biological function, the complex development of the cochlea enables us to study organogenesis, pluripotency, plasticity, cell fate specification, differentiation and pattern formation – processes that are essential aspects of development for all biological systems.

My goal is to understand developmental biology of the inner ear, its relation to diseases and ultimately its role in regenerative medicine for the amelioration of hearing disorders.

My long-term interests are to understand the signaling and transcriptional networks that specify the non-regenerating mechanosensory hair cells - cells that detect sound, and primary auditory neurons - cells that connect the inner ear to the brain.

I implement an interdisciplinary approach drawing from my diverse training and lead a dynamic collaborative research program.

With my trainees I focus on three main areas:

Wnt signaling in hair cell development and regeneration

We are actively pursuing understanding this pathway and down-stream targets for potential translational impact, currently focusing on the regenerative capacity of this pathway in the cochlea, as well as novel transcriptomic and epigenetic screens of homeostatic and regenerating mouse and human inner ear tissue.

Regeneration of auditory neurons

We are utilizing gene therapy to directly reprogram endogenous glial cells that surround primary auditory neurons and survive after neuron loss, into regenerated neurons. 

Our recent success clearly demonstrates that this is possible in vitro as we have been able to reprogram glial cells into induced neurons by overexpression of neurogenic transcription factors. 

Next we plan to proceed with a preclinical mouse model of neuropathy and perform these experiments in vivo. 

Understanding the biology of the blood-labyrinth barrier

We are working on mapping the biology of the blood-labyrinth barrier and uncovering the mechanisms for degeneration in the aged inner ear.

This will enable unprecedented advancement for the treatment of multiple inner ear disorders when combined with a regenerative medicine approach as well as methods for allowing non-invasive vascular delivery of therapeutics to the inner ear.

Selected Publications

Nyberg, S., Abbot, J., Shi, XR., Steyger, P., and Dabdoub, A. (2018). Delivery of therapeutics to the inner ear through the vasculature: How different is the blood-labyrinth barrier from the blood-brain barrier? In Press. Science Translational Medicine.

Meas, S., Zhang, CL., and Dabdoub, A. (2018). Reprograming glia into neurons in the peripheral auditory system as a solution for sensorineural hearing loss: lessons from the central nervous system. Frontiers in Molecular Neuroscience. 11:77. 10.3389/fnmol.2018.00077.

Noda, T., Meas, S., Nogami, J., Amemiya, Y., Uchi, R., Ohkawa, Y., Nishimura, K., and Dabdoub, A. (2018). Direct reprograming of spiral ganglion non-neuronal cells into neurons: Towards ameliorating sensorineural hearing loss by gene therapy. Frontiers in Cell and Developmental Biology. 6:16. 10.3389/fcell.2018.00016.

Nishimura, K., Noda, T., and Dabdoub, A. (2017). Dynamic expression of Sox2, Gata3, and Prox1 during primary auditory neuron development in the mammalian cochlea. PLoS One. 12(1):e0170568.

Mulvaney, JF., Thompkins, C., Noda, T., Nishimura, K., Sun, WW., Lin, S-Y., Coffin, A., and Dabdoub, A. (2016). Kremen1 regulates mechanosensory cell development in the mammalian cochlea and zebrafish lateral line. Scientific Reports. 6, 31668.

Geng, R., Noda, T., Mulvaney, JF., Lin, VY., Edge, A., and Dabdoub, A. (2016). Comprehensive expression of Wnt signaling pathway genes during development and maturation of the mouse cochlea. PLoS One. 11(2):e0148339.

Mulvaney, JF., Amemiya, Y., Freeman, S., Ladher, R., and Dabdoub, A. (2015). Molecular cloning and functional characterization of chicken Atonal homologue 1: a comparison with human Atoh1. Biology of the Cell. 107(2):41-60.

Mulvaney, JF., and Dabdoub, A. (2014). Long-term time lapse imaging of mouse cochlear explants. Journal of Visualized Experiments. 93:52101.

Nishimura, K., Weichert, RM., Liu, W., Davis, RL., and Dabdoub, A. (2014). Generation of induced neurons by direct reprogramming in the mammalian cochlea. Neuroscience. 275:125-35.

Shi, F., Lingxiang, H. Jacques, B., Mulvaney J., Dabdoub, A., and Edge AS. (2014). -catenin is required for hair cell differentiation in the cochlea. Journal of Neuroscience. 34:6470-6479.

Jacques, B., Montgomery, WH., Uribe, PM., Yatteau, A., Asunicon, JD., Resendiz, G., Matsui, JI., and Dabdoub, A. (2014). The role of Wnt/-catenin signaling in proliferation and regenerationof the developing basilar papilla and lateral line. Developmental Neurobiology. 74:438-56.

Mulvaney, JF., Yatteau, A., Sun, WW., Jacques, B., Takubo, K., Suda, T., Yamada, W., and Dabdoub, A. (2013). Secreted factor R-spondin 2 is involved in refinement of patterning of the mammalian cochlea. Developmental Dynamics. 242:179-188.

Jacques, B., Puligilla, C., Weichert RM., Ferrer-Vaquer, A., Hadjantonakis, AK., Kelley, MW., and Dabdoub, A. (2012). A dual function for canonical Wnt/-catenin signaling in the developing mammalian cochlea. Development. 139:4395-4404.

Macheda, ML., Sun, WW., Kugathasan, K., Hogan, BM., Zhang, YF., Jacques BE., Lieschke, GJ., Dabdoub, A., and Stacker, SA. (2012). The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling. Journal of Biological Chemistry. 287(35):12-23.

Mulvaney, JF. and Dabdoub, A. (2012). Atoh1, an essential transcription factor in neurogenesis, intestinal and inner ear development: Function, regulation and context dependency. Journal of the Association for Research in Otolaryngology. 13:281-293.