Tom Glaser, M.D., Ph.D.
4405A Tupper Hall
Genetic basis of mammalian eye development and congenital eye malformations
We study genetic mechanisms of vertebrate eye development, evolutionary conservation of gene networks, and transcriptional regulation. Our major interests include early patterning of the optic primordia and retinal cell fate specification. We use mutant and transgenic mice, human pedigrees segregating congenital eye malformations, and a variety of genomic, molecular and cell-based techniques. Current lab projects focus on ganglion cells – the first-born retinal neurons whose axons form the optic nerves and relay all visual information from the eye to the brain, fate symmetry, bHLH transcription factors, Notch signaling, the retinoid pathway, and molecular identification of new eye disease loci. Among these, we are investigating how mutations restricting retinoid (vitamin A) transport across the placenta cause maternally inherited eye malformations; how germ-line insertional translocations disrupt SOX3 transcription, reprogram cell fates, and cause a wide variety of hereditary diseases; and how founder gene mutations may elevate the incidence of severe eye defects in Chuuk state, Micronesia.
Research Support - Principal Investigator
- NIH R01 EY019497-09 Genetic Basis of Congenital Anophthalmia. Through April 30, 2022.
See: An updated list of current publications on PubMed »
Miesfeld JB, Ghiasvand NM, Marsh-Armstrong B, Marsh-Armstrong N, Miller EB, Zhang P, Manna SK, Zawadzki RJ, Brown NL and Glaser T. The Atoh7 remote enhancer provides transcriptional robustness during retinal ganglion cell development. Proc Natl Acad Sci USA 117:21690-21700 (2020).
Davis ES, Voss G, Miesfeld JB, Zarate-Sanchez J, Voss SR and Glaser T. The rax homeobox gene is mutated in the eyeless axolotl, Ambystoma mexicanum. Developmental Dynamics 1-15, https://doi.org10.1002/dvdy.246 (2020).
Kaukonen M, Woods S, Ahonen S, Lemberg S, Hellman M, Hytönen MK, Permi P, Glaser T and Lohi H. Maternal inheritance of a recessive RBP4 defect in canine congenital eye disease. Cell Reports 23:2643-2652 (2018)
Chou CM, Nelson C, Tarlé S, Pribila, J, Bardakjian T, Woods S, Schneider A and Glaser T. Biochemical basis for dominant inheritance, variable penetrance and maternal effects in RBP congenital eye disease, Cell 161, 634-646 (2015).
Prasov L and Glaser T. Dynamic expression of ganglion cell markers in retinal progenitors during the terminal cell cycle. Mol Cell Neurosci 2012;50:160-168.
Prasov L and Glaser T. Pushing the envelope of retinal ganglion cell genesis: context dependent function of Math5 (Atoh7). Dev Biol 2012;368:214-230.
Prasov L, Nagy M, Rudolph DD and Glaser T. Math5 (Atoh7) gene dosage limits retinal ganglion cell genesis. Neuroreport 2012;23:631-634.
Prasov L, Masud T, Khaliq S, Mehdi SQ, Abid A, Oliver ER, Silva ED, Lewanda AF, Brodsky MC, Borchert M, Kelberman D, Sowden JC, Dattani MT and Glaser T. ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous. Hum Molec Genet 2012;21:3681-3694.
Brzezinski JA, Prasov L and Glaser T. Math5 defines the ganglion competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. Dev Biol 2012;365:395-413.
Ghiasvand NM, Rudolph DR, Mashayekhi M, Brzezinski JA, Goldman DJ and Glaser T. Deletion of a remote enhancer for ATOH7 disrupts neurogenesis, causing nonsyndromic congenital retinal nonattachment. Nature Neurosci 2011;14:578-586.
Prasov L, Brown NL and Glaser T. A critical analysis of Atoh7 (Math5) mRNA splicing in the developing mouse retina. PLoS ONE 2010;5(8):e12315.
Saul SM, Brzezinski JA, Altshuler RM, Shore SE, Rudolph DD, Kabara LL, Halsey KE, Hufnagel RB, Dolan DF, Glaser T. Math5 expression and function in the central auditory system. Mol Cell Neurosci 2008;37:153-169.
Brzezinski JA , Brown NL, Tanikawa A, Bush RA, Sieving PA, Vitaterna M, Takahashi J and Glaser T. Abnormal circadian behavior and retinal electrophysiology in Math5 mutant mice. Invest Ophthal Vis Sci 2005;46:2540-2550.
Oliver ER, Saunders TL, Tarle SA and Glaser T. Ribosomal protein L24 defect in Belly spot and tail (Bst), a mouse Minute. Development 2004;131:3907-3920.
Tucker P, Laemle L, Munson A, Kanekar S, Oliver ER, Brown N, Schlecht H, Vetter M, and Glaser T. The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene. Genesis 2001;31:43-53.
Brown NL, Patel S, Brzezinski J, and Glaser T. Math5 is required for retinal ganglion cell and optic nerve formation. Development 2001 Jul;128:2497-2508.
Lauderdale JD, Wilensky JS, Oliver ER, Walton DS, and Glaser T. 3’ deletions cause aniridia by preventing PAX6 expression. Proc. Natl. Acad. Sci. USA 2000;97:13755-13759.
Brown NL, Kanekar S, Vetter ML, Tucker PK, Gemza D, and T Glaser. Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of neurogenesis. Development 1998;125:4821-4833.
Glaser TM, Jepeal L, Edwards JG, Young SR, Favor J and RL Maas. PAX6 gene dosage effect in the family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nature Genetics 1994;7:463-471.
Glaser TM, Walton DS and RL Maas. Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nature Genetics 1992;2:232-239.
- MDS 402 Medical Endocrinology, Nutrition, Reproduction and Genetics, Spring
- GGG 291 History of Genetics, Fall
- Animal Genomics
- Human Genetics and Genomics
- Molecular Medicine
- University of Michigan, Jerome W. Conn Award for Distinguished Research
- American Society for Clinical Investigation
- National Eye Advisory Council, NIH
- National Eye Institute
- National Institute for General Medical Sciences
- National Institutes of Health
- The Glaucoma Foundation