Preferred Name: Richard A. Gatti
Gatti is interested in translational research, including both the development of diagnostic assays and finding new drugs to treat genetic disorders. His research focuses on DNA repair disorders, using ataxia-telangiectsia (A-T) as the primary working model. The lab collaborates with investigators in many other countries. Ongoing projects include: 1) identification of genes that cause hypersensitivity to ionizing radiation, 2) identification of chemicals that correct the effects of specific types of mutations in the ATM gene, 3) better diagnostic assays for A-T, and 4) identification of chemicals that might be useful in combating a "dirty bomb" attack in a major city. The Gatti lab was the first at UCLA to localize a gene to a particular chromosome by linkage analysis (1988). This was the gene for A-T. An international consortium was then formed to fine map the region of interest on chromosome 11q22-23. Seven years later the Israeli members of the consortium successfully cloned the ATM gene from within this region. The ATM protein is a serine/threonine kinase that phosphorylates over 700 substrates, impacting primarily on cell cycle checkpoints and DNA repair signaling cascades. These findings have accounted for the pleiotropic A-T syndrome, which includes cancer susceptibility, radiation sensitivity, immunodeficiency, a progressive loss of balance, and specific chromosome translocations. The lab identifies ~30 new A-T patientsper year, and has characterized the majority of the ~700 unique ATM mutations (www.LOVD.nl/ATM). The team is now trying to characterize drugs that induce the expression of full length, functional ATM protein in A-T cells lacking the protein due to nonsense-type mutations and in others that carry splicing mutations. A novel high throughput screen was developed and ~70,000 chemicals were tested to identify small molecule readtrhrough (SMRT) compounds. These drugs promise to impact upon the treatment of most genetic diseases and perhaps upon cancer-prone individuals as well. The lab has the largest repository of cell lines from A-T patients, an important resource for these ongoing studies.
Diagnostic Testing Information