Michael A. Walter |
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| Professor, Medical Genetics and Ophthalmology | |
| Email address: mwalter@ualberta.ca Fax number: 780-492-6934 Phone number (office): 780-492-9044 Phone number (lab): 780-492-9805 |
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Academic Degrees and Training |
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Current Research Interests |
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Investigation of the role of the PITX2 and FOXC1 transcription factors in eye development and glaucoma My laboratory has focused in recent years upon investigating the function in the human eye of two transcription factors, PITX2 and FOXC1. Both PITX2 and FOXC1 function to regulate the express of other genes during development, but also continue to have important roles in normal adult eye function. Mutations of either PITX2 or FOXC1 result in human Axenfeld-Rieger (AR) malformations. Patients with AR malformations have eye defects and may also present with dental, jaw, and umbilical anomalies. About 50% of AR patients develop glaucoma, a progressive blindness. Research from the Walter laboratory has demonstrated that gene mutations found in AR patients result in either too little or too much PITX2 or FOXC1 transcriptional activity. We are also combining computer-based modeling with detailed cell biology and biochemistry to yield models of PITX2 and FOXC1 with predictive value. Efforts are underway to identify the genes that are regulated by either PITX2 or FOXC1 in the eye in order to determine the gene pathways that leads to glaucoma in AR patients. As well, we are also isolating other proteins that interact with PITX2 or FOXC1 to better understand how these two transcription factors normally function. It is our hope that better understanding of the function of PITX2 and FOXC1 together with knowledge of the genes regulated by these two transcription factors will lead to improved glaucoma detection and treatments. |
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Selected Publications |
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R. Brian Lowry, Douglas B. Gould, Michael A. Walter, Paul R. Savage (2006) Absence of PITX2, BARX1 and FOXC1 Mutations in the De Hauwere Syndrome (Axenfeld-Rieger Anomaly, Hydrocephaly, Hearing Loss): A 25 Year Fllow Up. Am J Med. Genet. (in press) Y. Tamimi, J.M. Skarie, T. Footz, F.B. Berry, B. Link, M.A. Walter (2006) FGF19 is a target for FOXC1 regulation in ciliary body derived cells. Human Molecular Genetics 15(21): 3229-40 Y.A. Ito, T. Footz, T.C. Murphy, Winnie Courtens, M. A. Walter (2006) FOXC1 function is severely disrupted by a novel L130F missense mutation if FOXC1. Arch. Ophthalmology (In Press) M. Hermina Strungaru, Irina Dinu, M.A. Walter (2006) Genotype-Phenotype correlations in Axenfeld-Rieger Malformation and glaucoma patients with FOXC1 and PITX2 mutations. Investigative Ophthalmology Vision Science 48(1):228-37 A. Vincent, G. Billingsley, M. Priston, T. Glaser, E. Oliver, M.A. Walter, R. Ritch, A. Levin, E. Héon (2006) Further support of the role of CYP1B1 in patients with Peters anomaly. Molecular Vision 12:506-10 F.B. Berry, F. Mirzayans, M.A. Walter. (2006) Regulation of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase signaling cascade. J Biol Chem. 281(15): 10098 – 104. Impact factor: 7.6 Berry F.B., Lines M.A., Oas J.M., Footz T., Underhill D.A., Gage P.J., Walter M.A., Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld–Rieger syndrome and anterior segment dysgenesis. Hum Mol Genet, 2006. 15(6): p. 1-15. Impact factor: 7.8 Berry FB, Tamimi Y, Carle MV, Lehmann OJ, Walter MA. (2005) The establishment of a predictive mutational model of the Forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis. Hum Mol Genet. 14(18): 2619-2627. Impact factor: 7.8 F.B. Berry, M.A. O’Neill, M. Coca-Prados, M.A. Walter. (2005) FOXC1 transcriptional regulatory activity is impaired by PBX1 in a Filamin A mediated manner. Mol and Cell Biol 25(4): 1415-1424. Impact factor: 7.8 De Becker, I, Walter M, Noel LP. (2004) Phenotypic variations in patients with a 1630 A>T point mutation in the PAX6 gene. Can J Ophthalmol. 39(3):272-8 Lab Personnel |
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