| Milan
Jamrich, Ph.D. |
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Professor, Departments of Molecular and
Human Genetics and Molecular & Cellular
Biology; Programs in Developmental Biology and Cell & Molecular
Biology
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RESEARCH
INTERESTS:
We have isolated a Xenopus forkhead gene Xlens1 that is the earliest marker of lens formation and is involved in the control of lens proliferation and differentiation (Kenyon et al.,1999). We have cloned and characterized its murine functional homologue, the forkhead gene Foxe3, which is expressed in the early stages of mouse lens formation. Foxe3, like Xlens1, is expressed in the initial stages of lens induction. It turns off its expression in differentiating fiber cells and remains active only in the relatively undifferentiated, proliferative cells of the anterior lens epithelium. Foxe3 maps to a region on chromosome 4 that contains the dysgenetic lens locus. We have found that two mutations in the forkhead box of the Foxe3 allele from dyl mice cause amino acid changes in positions thought to be essential for the structure and function of winged helix domains (Brownell et al., 2000). Furthermore, we have found that a mutation affecting C-terminal region of the human FOXE3 protein is responsible for anterior segment dysgenesis and cataracts (Semina et al., 2000). We are currently testing gene therapy strategies that would correct this genetic defect.
SELECTED PUBLICATIONS: 2. Wang J, Cortina G, Wu SV, Tran R, Cho JH, Tsai MJ, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martin MG (2006). Mutant neurogenin-3 in congenital malabsorptive diarrhea. N. Engl. J. Med. 355: 270-280. 3. Medina-Martinez O, Brownell I, Amaya-Manzanares F, Hu Q, Behringer RR, Jamrich M (2005). Severe defects in proliferation and differentiation of lens cells in Foxe3 null mice. Mol. Cell. Biol. 25: 8854-8863. 4. Van Raay TJ, Moore, KB, Iordanova I, Steele M, Jamrich M, Harris WA, Vetter, ML (2005). Frizzled 5 Signaling Governs the Neural Potential of Progenitors in the Developing Xenopus Retina. Neuron 46: 23-36. 5. Tseng HT, Shah R, Jamrich M (2004). Function and regulation of FoxF1 during Xenopus gut development. Development 131: 3637-3647. 6. Zhang L, El-Hodiri H, Ma HF, Zhang X, Servetnick M, Wensel TG, Jamrich M (2003). Targeted expression of the dominant negative FGFR-4a in the eye using Xrx1A regulatory sequences interferes with normal retinal cell development. Development 130: 4177-4186. 7. Semina EV, Brownell I, Murray JC, Jamrich M (2001). Mutations in the human forkhead transcription factor FOXE3 are associated with anterior segment ocular dysgenesis and cataracts. Hum. Mol. Genet. 10: 231-236. 8. Kenyon K, Moody S, Jamrich M (1999). A novel fork head gene mediates early steps in Xenopus lens formation. Development 126: 5107-5116. 9. Mathers PH, Grinberg A, Mahon KA, Jamrich M (1997). The Rx homeobox gene is essential for vertebrate eye formation. Nature 387: 603-607. For more publications, see listing of Dr. Jamrich's publications on Pub Med. CONTACT INFORMATION: Milan Jamrich, Ph.D. Department of Molecular and Human Genetics Baylor College of Medicine One Baylor Plaza Houston, Texas 77030, U.S.A. Telephone: 713-798-5278 |
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