Andy Groves, Ph.D.
Professor of Molecular and Human Genetics
B.A., University of Cambridge, 1988
Ph.D., Ludwig Institute for Cancer Research, University College London, 1992
Postdoc, California Institute of Technology, 1999
My laboratory uses the inner ear as a model system to address fundamental questions in developmental biology and regeneration. The transformation of a simple piece of epithelium – the otic placode - into a sensory organ of extreme morphological complexity provides an opportunity to study questions of competence, induction, pattern formation, cell-type differentiation and morphogenesis. We are using the complementary approaches of chick embryology and mouse genetics to address these problems. We have shown that the FGF and Wnt signaling pathways are critical in inducing the otic placode from embryonic ectoderm, and we are currently characterizing two novel Forkhead transcription factors that may mediate these inductive events. We are examining signaling pathways that specify the formation of the six auditory and balance sense organs of the ear and regulate the fine-grained and beautifully stereotyped pattern of sensory hair cells in these organs. We are also interested in trying to understand the mechanisms of how different sensory organs, such as the organ of Corti in the cochlea, arose during vertebrate evolution.
Sensory hair cells can be destroyed by prolonged exposure to loud noises, or by certain types of antibiotics or chemotherapy drugs. Mammalian hair cells are not replaced after damage, whereas non-mammalian vertebrates such as birds are able to achieve full functional recovery in a matter of weeks by inducing neighboring supporting cells to divide and replace lost hair cells. In an attempt to bring basic research to bear on this clinical problem, we have recently shown that supporting cells in the neonatal mouse cochlea have the capacity to divide and differentiate into hair cells, but that this capacity is largely lost by two weeks of age. This loss of regenerative capacity is due partly to changes in the regulation of cyclin-dependent kinase inhibitors such as p27Kip1. We are also investigating the role of Notch pathway-mediated lateral inhibition in preventing the production of new hair cells after injury.
- Basch ML, Ohyama T, Segil N, Groves AK (2011). Canonical Notch signaling is not necessary for prosensory induction in the mouse cochlea: insights from a conditional mutant of RBPjkappa. J. Neurosci. 31(22): 8046-58. PubMed PMID: 21632926
- Ohyama T, Basch ML, Mishina Y, Lyons KM, Segil N, Groves AK (2010). BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J. Neurosci. 30(45): 15044-51. PubMed PMID: 21068310
- Doetzlhofer A, Basch ML, Ohyama T, Gessler M, Groves AK, Segil N (2009). Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev. Cell 16(1): 58-69. PubMed PMID: 19154718
- Jayasena CS, Ohyama T, Segil N, Groves AK (2008). Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development 135(13): 2251-61. PubMed PMID: 18495817
- Raft S, Koundakjian EJ, Quinones H, Jayasena CS, Goodrich LV, Johnson JE, Segil N, Groves AK (2007). Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development 134(24): 4405-15. PubMed PMID: 18039969
- White PM, Doetzlhofer A, Lee YS, Groves AK, Segil N (2006). Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441(7096): 984-7. PubMed PMID: 16791196
- Ohyama T, Mohamed OA, Taketo MM, Dufort D, Groves AK (2006). Wnt signals mediate a fate decision between otic placode and epidermis. Development 133(5): 865-75. PubMed PMID: 16452098
- Martin K, Groves AK (2006). Competence of cranial ectoderm to respond to Fgf signaling suggests a two-step model of otic placode induction. Development 133(5): 877-87. PubMed PMID: 16452090
- Ohyama T, Groves AK (2004). Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis 38(4): 195-9. PubMed PMID: 15083520
Andy Groves, Ph.D.
Department of Neuroscience
Baylor College of Medicine
One Baylor Plaza, MS BCM295
Houston, TX, 77030, U.S.A.