Joined the faculty:  1996

Affiliations: Department of Otolaryngology, Center for Neuroscience

Teaching:  BMS 700, BMS 715, CCMD 793D, NBAN 795

Office: 102 Otolaryngology
Phone: (304) 293-0271
Fax: (304) 293-2902
Email: pmathers@hsc.wvu.edu

Recent advances in developmental biology have allowed us to begin to understand the molecular mechanisms that lead to organ formation in the early vertebrate embyro. My laboratory is specifically interested in studying genes that are critical for forming the sensory organs of the head: the eyes, the ears, and the nose. Using both modern molecular and classical developmental biology techniques, we are analyzing the function of early regulatory control genes in the synthesis of these sensory organs.

We have isolated the genes for a family of DNA-binding proteins that appear to be required for making the stem cells that will give rise to the differentiated neural retina, the light-sensing layers of the eye. This gene family, called Rx for retinal homeobox, is extremely well conserved across species, with members found in mammals, frogs, fish, and fruit flies. When this gene is deleted from mice using a molecular technique called gene knockout, the result is mice born without eyes. Therefore, this gene is crucial for proper eye development, and is one of only a few master regulators of eye formation.

In the future, we hope to better characterize the role that Rx plays in activating or inhibiting genes in the cascade that leads to eye formation. In addition, we hope to isolate other genes required for formation of the ear and/or the nose.

  References:

• Howell DM, Morgan WJ, Jarjour AA, Spirou GA, Berrebi AS, Kennedy TE, and Mathers PH. Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus. J Comp Neurol 504: 533-549, 2007.
   
• Hoffpauir BK, Grimes JL, Mathers PH, and Spirou GA. Synaptogenesis of the calyx of Held: rapid onset of function and one-to-one morphological innervation. J Neurosci 26: 5511-5523, 2006.
   
• Ma Y, Hu H, Berrebi AS, Mathers PH, and Agmon A. Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J Neurosci 26: 5069-5082, 2006.
   
• Voronina VA, Kozlov S, Mathers PH, and Lewandoski M. Conditional alleles for activation and inactivation of the mouse Rx homeobox gene. Genesis 41: 160-164, 2005.
   
• Bailey TJ, El-Hodiri H, Zhang L, Shah R, Mathers PH, and Jamrich M. Regulation of vertebrate eye development by Rx genes. Int J Dev Biol 48: 761-770, 2004.
   
• Voronina VA, Kozhemyakina EA, O'Kernick CM, Kahn ND, Wenger SL, Linberg JV, Schneider AS, and Mathers PH. Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea. Hum Mol Genet 13: 315-322, 2004.