David R. Cox
Title
Professor
Department
Genetics
Research Interests
Human genetics; molecular genetic basis of human disease; human disease; human genome analysis.
Phone
725-8043
Fax
725-8058
Address
SUMC M-336
Mail Code: 5120
Faculty Research Description
Our laboratory uses molecular and somatic cell genetic techniques to study the molecular basis of human genetic disease, with a special focus on human neurogenetic disease. Since these studies often require the availability of high resolution genetic and physical maps of human chromosomes, our research interests also include the development of techniques for generating such maps of the human genome.
A major focus of our research is the identification of human disease genes on the basis of their chromosomal location. One project involves the identification of chromosome 21 DNA variants that are enriched in Down syndrome individuals as compared to the normal population. The goal of this project is to identify chromosome 21 genes associated with lethality and/or severe mental retardation. In another project, we are using interval mapping of the entire human genome, in conjunction with several large, extended families, to identify loci that play a major role in elevated blood pressure in humans.
A second research focus is the use of model organisms to study the functional consequences of mutations in human genes. In one project, we use the yeast "two-hybrid" assay to gain a better understanding of the mechanisms by which mutations in the human tumor suppressor gene, merlin, result in human brain tumors. In another project, we have collaborated with Dr. Richard Myers to show that a mutation in a G-protein coupled potassium channel gene that maps to human chromosome 21 results in abnormal neuronal development in mice. We are presently investigating the consequences of altered dosage of this gene for neuronal development and differentiation. In another recent study, also carried out in collaboration with the Myers lab, we have found that mutation in another human chromosome 21 gene, cystatin B, results in a progressive inherited form of human epilepsy. Studies are underway to clarify how deficiency of the protease inhibitor, which is the normal protein product of the cystatin B gene, results in abnormal neuronal electrical activity and neuronal cell death.
Fatham, M. and Cox DR. A novel in vivo method to detect DNA sequence Variation. Cold Spring
Harbor Lab. Press. 5:474-482 (1995)
Patil N., Cox DR., Bhat D., Faham M., Myers RM., and Peterson AS. A potassium channel mutation in
weaver mice implicates membrane excitability in granule cell differentiation. Nature Genetics
11:126-129. (1995)
Slesinger PA., Patil N., Liao YJ., Jan YN, Jan LY., and Cox DR. Functional effects of the mouse
weaver mutation on G protein-gated inwardly rectifying K+ channels. Neuron 16:321-331. (1996)
Pennachio LA., Lehesjoki AE., Stone NE., Williour VL., Virtaneva K., Miao J., D'Amato E., Ramierz L,
Faham M., Koskiniemi M., Warrington JA., Norio R., de la Chapelle A., Cox DR., and Myers RM.
Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1). Scince 271:
1731-1734. (1996)
Johnson RL., Rothman AL, Xie J., Goodrich LV., Bare JW., Bonifas JM., Quinn AG., Myers RM., Cox
DR., Epstein EH jr., Scott MP. Human homolog of patched, a candidate gene for the basal cell nevus
syndrome. Science 272:1668-1671. (1996)
Areas of Study
Molecular Neurobiology
SBRC
Ph.D.