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

RESEARCH INTERESTS:
Molecular mechanisms controlling retinal development

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, also 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 identify new genes required for normal retinal development. Using a large set of microarray data, we have identified more than 100 new genes that are likely to be involved in eye development and/or function. We are systematically deleting each of these genes and then carefully analyzing the loss-of-function phenotypes associated with each deletion using a full array of molecular, genetic, biochemical, and bioinformatic techniques. Many of these newly identified genes have produced striking retinal phenotypes and are currently under intense investigation. Many new projects are available.

In our second approach, we are using mouse knockout and knockin technology to determine the function of eight new genes whose expression is specifically enriched in the retina during development. Homologs of several of these genes are also being studied in zebrafish. These genes include a transcription factor, a protein phosphatase, a phospholipase, a putative calcium channel, a protein kinase, and a transportin. Several knockout constructs have already been generated and electroporated into ES cells and we expect to have targeted knockouts of all eight genes within the next year. Complete functional studies will be conducted and several new projects are therefore 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 12 genes known to be associated with LCA these account for only about 70% of all cases. Therefore, several new loci remain to be identified. In collaboration with Drs. 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. Several new projects are possible in this area as well.

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SELECTED PUBLICATIONS:
1. Davis RJ, Harding M, Moayedi Y, Mardon G (2008). Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development. Genesis 46: 205-213.

2. 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: 125-141.

3. 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. *These authors contributed equally to this work. **These laboratories contributed equally to this work. Genome Res. 16: 466-476.

4. 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: 2895-2905.

5. Chen R, Mardon G (2005). Keeping an eye on the fly genome. Dev. Biol. 282: 285-293.

6. Pappu K, Mardon G (2004). Genetic control of retinal specification and determination in Drosophila. Int. J. Dev. Biol. 48: 913-924.

7. Frankfort B, Mardon G (2004). Senseless represses nuclear transduction of Egfr pathway activation. Development 131: 563-570.

8. Pappu K, Chen R, Middlebrooks BW, Woo K, Heberlein U, Mardon G (2003). Mechanism of hedgehog signaling during early Drosophila eye development. Development 130: 3053-3062.

9. Frankfort B, Mardon G (2002). R8 Development in the Drosophila Eye: A Paradigm for Neural Selection and Differentiation. Development 129: 1295-1306.

10. 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: 403-414.

11. 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: 893-903.

For more publications, see listing on Pub Med.

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CONTACT INFORMATION:
Graeme Mardon, Ph.D.
Department of Pathology
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.

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

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Last modified: 6/2008