Michael Walter

Michael Walter

Professor and Chair

Medical Genetics
8-39 Medical Sciences Building
(780) 492-4172
(780) 492-1998 (fax)
mwalter@ualberta.ca


Academic Degrees and Training

  • BSc: University of Guelph (1980)
  • PhD: University of Toronto (1990)
  • Postdoctoral training: Imperial Cancer Research Fund, London, England (1992)
  • Postdoctoral training: Cambridge University, Cambridge, England (1993)

Current Research Interests

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.

Selected Publications

Footz, T., Dubois, S., Sarfarazi, M., Raymond, V., Walter, MA., Co-variation of STI1 and WDR36/UTP21 alters cell proliferation in a glaucoma model. Molecular Vision 2011; 12:1957-1969

Strungaru, M., Footz, T., Liu, Y., Berry, F., Belleau, P., Semina, E., Raymond, V., Walter, MA., PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3. Invest Ophthalmol and Vis Sci (in press)

Acharya, M., Huang, L., Fleisch VC., Allison, WT., Walter, MA. A complex regulatory network of transcription factors critical for ocular development and disease. Hum Mol Genet. Feb 2011

Ye, M., Berry-Wynne, KM., Asai-Coakwell, M., Sundaresan, P., Footz, T., French, CR., Abitbol, M., Fleisch, VC., Corbett, N., Allison, WT., Drummond, G., Walter, MA., Underhill TM, Waskiewicz AJ, Lehmann, OJ. Mutation of the Bone Morphogenetic Protein GDF3 causes ocular and skeletal anomalies. Hum Mol Genet. 2010 Jan 15;19(2):287-98. Epub 2009 Oct 28

Fetterman, C.D., Mirzayans, F., Walter, MA. (2009). Characterization of a novel FOXC1 mutation, P297S, identified in two individuals with anterior segment dysgenesis. Clin Genet 2009: 76: 296-299 doi: 10.1111/j.1399-0004.2009.01210.x

Acharya, M., Lingenfelter, DJ., Huang, L., Gage, PJ., Walter, MA. Human PRKC Apoptosis WT1 Regulator in a Novel PITX2-Interacting Protein that Regulates PITX2 Transcriptional Activity in Ocular Cells. Biol Chem. 2009 Dec 11;284(50):34829-38. Epub 2009 Oct 2.

Ito, YA., Footz, TK., Berry, FB., Mirzayans, F., Yu, M., Khan, AO., Walter, MA. Severe molecular defects of a novel FOXC1 W152G mutation result in aniridia. Invest Ophthalmol Vis Sci Aug 2009; 50(8):3573-9. Epub 2009 Mar 11

Footz TK, Idrees F, Acharya M, Kozlowski K, Walter MA. Analysis of mutations of the PITX2 transcription factor found in Axenfeld-Rieger Syndrome patients. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2599-606. Epub 2009 Feb 14.

Footz TK, Johnson JL, Dubois S, Boivin N, Raymond V, Walter MA. Glaucoma-associated WDR36 Variants Encode Functional Defects in a Yeast Model System. Hum Mol Genet. 2009 Apr 1;18(7):1276-87. Epub 2009 Jan 15

Chanda, B., Asai-Coakwell, M., Ye, M., Mungall, AJ., Barrow, M., Dobyns, WB., Behesti, H., Sowden, JC., Carter, NP., Walter, MA., Lehmann, OJ. (2008) A novel mechanistic spectrum underlies glaucoma associated chromosome 6p25 copy number variation. Hum Mol Genet. 2008 Nov 15;17(22):3446-58. Epub 2008 Aug 11.

Sharan, S., Mirzayans, F., Footz, TK., Walter, MA., Levin AV (2008) Elliptical anterior iris stromal defects associated with PAX6 gene sequence changes. Journal of AAPOS Volume: 12, Issue: 4, August, 2008, pp. 340-343.e2

Fetterman, CD., Rannala, B., Walter, MA. (2008) Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies. BMC Evolutionary Biology 2008 Sept 24

Huang, L., Chi, J., Berry, FB., Footz, TK., Sharp, M., Walter, MA. Human p32 is a novel FOXC1 – interacting protein that regulates FOXC1 transcriptional activity in ocular cells. Investigative Ophthalmology Vision Science 2008 Dec. Impact factor: 3.6

Berry, FB., Skarie, JM., Mirzayans, F., Fortin, Y., Hudson, TJ., Raymond, V., Link, BA., Walter, MA. FOXC1 is required for cell viability and resistance to oxidative stress in the eye through the transcriptional regulation of FOXO1A Hum Mol Genet. 2007 Nov 9; [Epub ahead of print] PMID: 17993506 [PubMed - as supplied by publisher]

Lowry, RB., Gould, DB., Walter, MA. Savage PR (2007) Absence of PITX2, BARX1, and FOXC1 mutations in De Hauwere syndrome (Axenfeld-Rieger anomaly, hydrocephaly, hearing loss): A 25-year follow up. Am J Med Genet A. 2007 May 7;143A(11):1227-1230

Ito, YA., Footz, TK., Murphy, TC., Courtens, W., Walter, MA. (2007) Analyses of a novel L130F missense mutation in FOXC1. Arch Ophthalmol. 2007 Jan;125(1):128-35

Strungaru, MH., Dinu, I., Walter, MA (2007) Genotype-Phenotype correlations in Axenfeld-Rieger Malformation and glaucoma patients with FOXC1 and PITX2 mutations. Investigative Ophthalmology Vision Science 48(1):228-37

Lab Personnel

Technicians

Tim Footz

Graduate Students

Fahed Elian
Adrian Lahola-Chomiak