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Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
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Graeme Mardon, Ph.D.

Graeme Mardon, Ph.D.

Professor, Department of Molecular and Human Genetics

Other Positions

Professor, Departments of Neuroscience, Pathology & Immunology, and Ophthalmology; Programs in Cell & Molecular Biology and Developmental Biology
Co-Director, Graduate Program in Molecular and Human Genetics
Program Director, NIH Training Grant T32 EY07102

Education

B.S., Haverford College, 1980
Ph.D., Massachusetts Institute of Technology, 1990
Postdoc, University of California, Berkeley, 1994

Research Interests

The primary goal of our research is to understand molecular mechanisms of retinal development with the ultimate goal of improving our ability diagnose, prevent, and treat human retinal disease. To this end, we are using three approaches, all in collaboration with Dr. Rui Chen, in the Department of Molecular and Human Genetics. The first two approaches use the mouse Mus musculus and the fruit fly Drosophila melanogaster as animal model systems to identify and determine the function of conserved genes required for normal retinal development. The third approach is to map new human retinal disease genes. In spite of substantial differences between vertebrate and insect retinal morphology, genetic mechanisms of retinal development have been conserved for more than 500 million years. Thus, study of the molecular and genetic pathways controlling Drosophila eye development has provided a valuable set of tools with which to decipher the development and function of the vertebrate retina.

Our main Drosophila project uses a combinatorial approach of genetics, genomics, and computational biology to dissect the roles of eyes absent and sine oculis, two conserved genes controlling retinal determination and differentiation. We are using ChIP-Seq to identify direct targets of the Sine oculis homeobox transcription factor as well as several other key proteins required for normal retinal development. In addition, we are using a novel genomic rescue strategy to definitively dissect the in vivo function of several conserved domains in these proteins. Finally, we are using transcriptional regulation of eyes absent as a paradigm for studying the relationship between chromatin remodeling and developmental regulation of this key retinal gene.

In our second approach, we are using mouse knockout and knockin technology to determine the function of several new genes whose expression is specifically enriched in the retina during development. These genes include a histone demethylase, a protein phosphatase, a phospholipase, a protein kinase, and a transcription factor. Germline transmission of several knockout constructs have already been generated and we expect to have targeted knockouts of all genes within the next year. Complete functional studies will be conducted and several new projects are available.

Our third project is to map new human disease genes associated with Leber Congenital Amaurosis (LCA), the most common cause of blindness in children. While there are 15 genes known to be associated with LCA, these account for only about 70 percent of all cases. Therefore, several new loci remain to be identified. In collaboration with Drs. Chen, Lupski, and Lewis, we are using whole genome linkage studies to map new LCA genes in 29 families. We have already identified one new putative disease gene and expect several more in the near future. Mouse models are being created for each new disease gene identified. These models will be used for phenotypic analysis and gene therapy studies.

Drosophila pupal eye disc over expressing the gene senseless

A Drosophila pupal eye disc over expressing the gene senseless, stained with antibodies to reveal cell membranes (purple) and the R7 and R8 photoreceptors (green).

Selected Publications

  1. Wang H, den Hollander AI, Moayedi Y, Abulimiti A, Li Y, Collin RW, Hoyng CB, Lopez I, Bray M, Lewis RA, Lupski JR, Mardon G, Koenekoop RK, Chen R (2009). Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. Am. J. Hum. Genet. 84(3): 380-7. [Pub Med]
  2. Li Y, Wang H, Peng J, Gibbs RA, Lewis RA, Lupski JR, Mardon G, Chen R (2008). Mutation Survey of Known LCA Genes and Loci in the Saudi Arabian Population. Invest. Ophthalmol. Vis. Sci. 50(3): 1336-43. [Pub Med]
  3. Pepple KL, Atkins M, Venken K, Wellnitz K, Harding M, Frankfort B, Mardon G (2008). Two-step selection of a single R8 photoreceptor: a bistable loop between senseless and rough locks in R8 fate. Development 135(24): 4071-9. [Pub Med]
  4. Davis RJ, Harding M, Moayedi Y, Mardon G (2008). Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development. Genesis 46(4): 205-13. [Pub Med]
  5. Pepple KL, Anderson AE, Frankfort BJ, Mardon G (2007). A genetic screen in Drosophila for genes interacting with senseless during neuronal development identifies the importin moleskin. Genetics 175(1): 125-41. [Pub Med]
  6. Ostrin EJ*, Li Y*, Hoffman K, Liu J, Zhang L, Mardon G**, Chen R** (2006). Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless. Genome Res. 16(4): 466-76. *These authors contributed equally to this work. **These laboratories contributed equally to this work. [Pub Med]
  7. Pappu KS, Ostrin EJ, Middlebrooks BW, Sili BT, Chen R, Atkins MR, Gibbs R, Mardon G (2005). Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund. Development 132(12): 2895-905. [Pub Med]
  8. Chen R, Mardon G (2005). Keeping an eye on the fly genome. Dev. Biol. 282(2): 285-93. [Pub Med]
  9. Pappu K, Chen R, Middlebrooks BW, Woo K, Heberlein U, Mardon G (2003). Mechanism of hedgehog signaling during early Drosophila eye development. Development 130(13): 3053-62. [Pub Med]
  10. Frankfort B, Mardon G (2002). R8 Development in the Drosophila Eye: A Paradigm for Neural Selection and Differentiation. Development 129(6): 1295-306. [Pub Med]
  11. Frankfort B, Nolo R, Zhang Z, Bellen H, Mardon G (2001). senseless repression of rough is required for R8 photoreceptor differentiation in the developing Drosophila eye. Neuron 32(3): 403-14. [Pub Med]
  12. Chen R, Amoui M, Zhang Z, Mardon G (1997). Dachshund and Eyes Absent Proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91(7): 893-903. [Pub Med]

More Publications (PubMed)

Awards and Honors

2008: Best Lecturer, 8-Stranded Beta-Barrel Jelly Roll Awards, Baylor College of Medicine
2002 and 2006: James M. Barr Award for Outstanding Retina Research Achievement
2001: Marc Dresden Excellence in Graduate Education Award, Baylor College of Medicine
1999: Brochstein Award for Outstanding Achievement in Retina Research

Contact Information

Graeme Mardon, Ph.D.
Department of Pathology
Baylor College of Medicine
One Baylor Plaza, MS BCM315
Houston, TX, 77030, U.S.A.

Phone: 713-798-8731
Fax: 713-798-3359
E-mail:

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