Suzanne L. Mansour, Ph.D.

I have worked for more than 30 years to elucidate the roles and regulation of FGF signaling in ear development as a means of understanding how this signaling system alone and in combination with other signaling systems is deployed to regulate human auditory and vestibular function. This work began with the serendipitous finding during my postdoctoral fellowship that the first non-selectable gene we targeted in mouse embryonic stem cells (int-2, now known as Fgf3) plays a role in induction of the endolymphatic duct and subsequent morphogenesis and function of the inner ear. My independent lab went on to discover the essential and redundant roles of Fgf3, Fgf10 and Fgf8 in mouse otic placode induction, and we subsequently identified new targets of FGF signaling in otic induction. We also defined unique as well as combinatorial roles for Fgf3 and Fgf10 in otic morphogenesis and neurogenesis, and have recently validated a system to inhibit the function of these genes at any stage of interest by doxycycline-induced expression of the extracellular domain of their receptor (FGFR2b). This acts as a dominant-negative ligand trap and allowed us to identify proximal downstream targets of FGF3/FGF10 at the early stages of otic morphogenesis. We have also investigated the auditory phenotypes of mouse models of human FGF gain-of-function syndromes, including Muenke syndrome. Our studies of this model uncovered a remarkable postnatal auditory supporting cell fate plasticity and ectopic hair cell production that have implications for developing treatments for Muenke syndrome and for hearing restoration strategies more generally. Thus, my lab has contributed in numerous ways to understanding the control of ear development at many different stages and we are poised to make additional breakthroughs in determining the timing, location and mechanism of FGF signaling regulating otic morphogenesis and neurogenesis, as well as making inroads into the roles of novel FGF target genes in inner ear development and function.

Urness LD, Wang X, Doan H, Shumway N, Noyes CA, Gutierrez-Magana E, Lu R, Mansour SL. Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis. Development. 2018 Dec 18;145(24):dev170142. doi: 10.1242/dev.170142.

Quadros RM, Miura H, Harms DW, Akatsuka H, Sato T, Aida T, Redder R, Richardson GP, Inagaki Y, Sakai D, Buckley SM, Seshacharyulu P, Batra SK, Behlke MA, Zeiner SA, Jacobi AM, Izu Y, Thoreson WB, Urness LD, Mansour SL, Ohtsuka M, Gurumurthy CB. Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins. Genome Biol. 2017 May 17;18(1):92. doi: 10.1186/s13059-017-1220-4.

Mansour SL, Li C, Urness LD. Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates. Genes Dev. 2013 Nov 1;27(21):2320-31. doi: 10.1101/gad.228957.113. Epub 2013 Oct 21.