Research Interests
The vertebrate inner ear develops from a simple piece of embryonic ectoderm called the otic placode to form one of the most complex sensory organs in the animal kingdom. The mammalian inner ear contains six groups of mechanosensory hair cells, five of which mediate our sense of balance (detecting linear and angular acceleration), and the sixth – the organ of Corti – detects sound. We are interested in the signals and transcriptional regulators that single out tissue destined to form the otic placode, and which sculpt its descendants to form a morphologically complex structure that generates the precise numbers of cells at the right time. We have identified a transcription factor, Foxi3, that appears to be expressed in the progenitors of all craniofacial placodes, and which is necessary for the entire inner ear to form. We are also investigating how signaling pathways such as Notch, BMPs and Wnts contribute to the intricate pattern of the inner ear.
We detect sound and balance information with exquisitely sensitive hair cells, which get their name from the hair-like bundle of actin-rich stereovilli that protrude from their apical surface. These cells are capable of detecting mechanical deflections at the sub-nanometer range, but with their great sensitivity comes great vulnerability. Hair cells can be killed by loud noise, the aging process, and certain drugs such as aminoglycoside antibiotics and platinum-containing chemotherapy drugs. Mammals, including humans, are unable to regenerate their hair cells after they are killed. However, other vertebrates such as birds, amphibians and fish are capable of mobilizing supporting cells to divide and transdifferentiate to hair cells, restoring both hearing and balance. We are trying to understand the roadblocks to hair cell regeneration in mammals, and how these blocks appear in the early life of mammals. We are experimenting with gene therapy and reprogramming strategies to try and promote hair cell regeneration and haring restoration in mammals.
Finally, we are interested in how mechanosensory hair cells arose during evolution. We are analyzing the transcriptional signatures of mechanosensory cells that detect sound or balance in fruit flies, cephalopods (squid) and our closest invertebrate relatives, the tunicates (or sea squirts), and comparing them with those of vertebrate hair cells. We hope to identify core gene and protein regulatory networks that are conserved during the evolution of mechanosensory cells.
Education and Training
1985-1988: Sidney Sussex College, Cambridge University, UK
Natural Science Tripos (Biochemistry)
1988-1992: Graduate Student, Ludwig Institute for Cancer Research,
University College / Middlesex Hospital Branch, London, UK
1992-1996: Research Fellow in Biology, California Institute of Technology
Laboratory Head: Dr. David Anderson
1997-1999: Senior Research Fellow in Biology, California Institute of Technology
Laboratory Head: Dr. Marianne Bronner
Research and Professional Experience
1999-2008: Section Chief, Department of Cell and Molecular Biology, House Ear Institute, Los Angeles
2000-2008: Adjunct Assistant Professor, Department of Cell and Neurobiology and Clinical Assistant Professor, Department of Otolaryngology, University of Southern California.
2008-2013: Associate Professor, Department of Neuroscience and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston
2013-2025: Professor and Vivian L. Smith Endowed Chair in Neuroscience (2018-2025), Department of Neuroscience and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston
2025-present: Professor and Head, Department of Developmental Biology, Washington University School of Medicine, St. Louis
Selected Publications
McGovern, M.M., Hosamani, I., Niu, Y., Nguyen, K.Y., Zong, C., and Groves, A.K. (2024). Expression of Atoh1, Gfi1, and Pou4f3 in the mature cochlea reprograms non-sensory cells into hair cells. PNAS, 121, e2304680121.
Thawani, A., Maunsell, H.R., Zhang, H., Ankamreddy, H. and Groves, A.K. (2023). The Foxi3 transcription factor is necessary for the fate restriction of placodal lineages at the neural plate border. Development 150, dev202047.
Mao, K., Borel, C., Ansar, M., Jolly, A., […] Groves, A.K., Lupski, J.R., Zhang, Q., Zhang, Y.-B., and Antonarakis, S.E. (2023). FOXI3 pathogenic variants cause one form of craniofacial microsomia. Nature Communications, 14:2026
Tao, L., Yu, H., Llamas, J., Trecek, T., Wang, X., Stojanova, Z., Groves, A.K. and Segil, N. (2021). Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration. Dev. Cell, 56, 1-15.
Jen, H.-I, Hill, M.C., Tao, L., Sheng, K., Cao, W., Zhang, H., Yu, H.V., Llamas, J., Zong, C., Martin, J.F., Segil, N. and Groves, A.K. (2019). Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1 . eLife, e44328. doi: 10.7554/eLife.44328.
Basch, M.L., Brown, R.M., Jen, H.-I, Semerci, F., Depreux, F., Edlund, R.K., Zhang, H., Norton, C.R., Gridley, T., Cole, S.E., Doetzlhofer, A., Maletic-Savatic, M., Segil, N. and Groves, A.K. (2016). Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates. eLife, 10.7554/eLife.19921
Li, T., Giagtzoglou, N., Eberl, D.F., Jaiswal, S.N., Jaiswal, M., Cai., T., Godt, D., Groves, A.K. and Bellen, H.J. (2016). The E3 ligase Ubr3 regulates Usher syndrome and MYH9-related disorder proteins in the auditory organs of Drosophila and mammals. eLife, 10.7554/eLife.15258.
Ohyama, T., Basch, M.L., Mishina, Y., Lyons, K., Segil, N. and Groves, A.K. (2010). BMP signaling is necessary for patterning the sensory and non-sensory regions of the developing mammalian cochlea. J. Neuroscience 30, 15044-15051.
Doetzlhofer, A., Basch, M.L., Ohyama, T., Gessler, M., Groves, A.K., and Segil, N. (2009). Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Developmental Cell 16, 58-69.
Raft, S., Koundakjian, E.J., Quinones, H., Jayasena, C.S., Goodrich, L.V., Johnson, J.E., Segil, N. and Groves, A.K. (2007). Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development. Development 134, 4405-4415.
White, P.M., Doetzlhofer, A., Lee, Y.-S., Groves, A.K. and Segil, N. (2006). Cochlear supporting cells retain the ability to divide and transdifferentiate into sensory hair cells. Nature 441, 984-987.
Groves, A.K. and Bronner-Fraser, M. (2000). Competence, specification and commitment in otic placode induction. Development 127, 3489-3499.
Shah, N.M., Groves, A.K., and Anderson, D.J. (1996). Alternative neural crest cell fates are instructively promoted by TGFb superfamily members. Cell 85, 331-343.
Groves, A.K., Barnett, S.C., Franklin, R.J.M., Crang, A.J., Mayer, M., Blakemore, W.F., and Noble, M. (1993). Repair of demyelinated lesions by transplantation of purified O‑2A progenitor cells. Nature 362, 453-455.