Dr.Michael Ebeid, Ph.D.

About us:

Our lab is interested in understanding the molecular mechanisms governing mammalian cochlear development, maturation, and aging. We utilize a variety of tools including mouse genetics, ex-vivo culture, cellular, molecular, imaging, and electrophysiological techniques in studying the cochlea. Our ultimate goal is to identify novel mechanisms in cochlear development and aging, then translate our research into therapeutic techniques to enhance repair/regeneration. 

Current members:

Dr. Michael Ebeid, PI

Dr. Hongji Zhang, Research Specialist/Lab manager

Jemma Ibrahim, MBS 26

Sahithy Yaramada MA 26

Karen John, CCOM 28

Riya Patel, CCOM 28

Selena Tian, CCOM 27


Current Projects:
1- The pathogeneis of Cytomegalovirus-induced cochlear pathology during early development

In collaboration with Dr. Tiwari at Midwestern and Drs. Zhang and Richter at Northwestern, this project aims to understand cochlear pathology induced by congenital Cytomegalovirus (cCMV) infection. cCMV is the leading non-genetic cause of sensorineural hearing loss in children, affecting 1 in 5 babies born with the virus. This project is utilizing ex-vivo and in-vivo approaches for modeling CMV infection during early cochlear development. Identifying pathways involved in cochlear dysfunction secondary to CMV infection will enable the development of new therapeutic strategies to treat hearing loss.

2- Investigate the role of Kolliker's organ in the development, maturation and function of the cochlea. 
Our lab has identified PRDM16 expression in the epithelial cells of the Kölliker’s organ (greater epithelial ridge). Utilizing loss-of-function mouse models, we were able to show Prdm16’s necessity for Kölliker’s organ development as well as the spiral limbus and the tectorial membrane. We further created and analyzed a conditional deletion model that established the Kölliker's organ as a developmental hub orchestrating the development of the spiral limbus and the tectorial membrane. Currently, we are investigating a secreted protein role in epithelial-mesenchymal signaling downstream Prdm16.

-*Ebeid, M, Barnas, K, Zhang, H, Yaghmour, A, Noreikaite, G, Bjork, BC. PRDM16 expression and function in mammalian cochlear development. Developmental Dynamics. 2022; 1- 18.

3- Identify the impact of ETV transcription factor deletion on the mouse organ of Corti .
We identified two ETV transcription factors (ETV4 and ETV5) operating downstream FGF signaling during cochlear development and responsible for cochlear lengthening. Deletion of these 2 transcription factors from the mesenchyme surrounding the cochlear duct led to shortening of the cochlear duct without impacting the patterning of sensory epithelium. Such findings enhance our understanding of how the mesenchyme contributes to cochlear epithelial development and thereby improve current methods for culturing and expanding sensory progenitors. This work was published in Hearing Research (2020). Currently, we are studying the three transcription factors (ETV1, ETV4 & ETV5) in cochlear supporting cell development and have shown an interesting phenotype in which the inner pillar cell identity is lost in this model. A manuscript is in preparation.
- Ebeid M, Huh SH. Mesenchymal ETV Transcription Factors Regulate Cochlear Length. Hearing Research (2020), 396,108039.

4- The effect of aging on recovery from hearing loss and sciatic neuropathy in the DTA mouse model upon induction of Schwann cell loss

Using the established DTA mouse model (PLP/CreER^T; ROSA26-eGFP-DTA) that specifically ablates the Plp1-expressing glial cells i.e. oligodendrocytes in the CNS and Schwann cells in the PNS upon induction with tamoxifen, we are characterizing the role of ageing in regeneration and remyelination mechanisms in the cochleae and the sciatic nerves of mature-adult and aging DTA mice. 

5- Wnt/β-catenin signaling in cochlear sensory patterning and supporting cell fate determination:
We have shown that β-Catenin transcriptional function is required to establish the inner pillar cell fate in the developing cochlea. Currently, we are utilzing both gain- and loss-of-function β-Catenin mouse models to study the postnatal role of β-Catenin in supporting cell survival and function.
- Ebeid M, Kishimoto I, Roy P, Zaidi MAA, Cheng AG, et al. (2023) β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development. PLOS Genetics 19(8): e1010925.

If you are interested in joining the lab, please reach out at mebeid@midwestern.edu