Richard A. Gatti, M.D.


Professor, Pathology and Laboratory Medicine

Professor In-Residence, Human Genetics

Member, Basic/Translational Research, Jonsson Comprehensive Cancer Center

Brain Research Institute

JCCC Cancer and Stem Cell Biology Program Area

Physics & Biology in Medicine GPB Home Area

Faculty, Cellular and Molecular Pathology PhD Program

Awards and Honors:

Children's Memorial Medical Center

Children's Memorial Medical Center

Karolinska Institutet

University of Minnesota Hospital and Clinic

Contact Information

Work Phone Number: (310) 825-7618
310 650 3431

Laboratory Address:

MRL 4609


Work Address:

MRL 4736
CAMPUS - 173216


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 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, specific chromosome translocations, and perhaps a resistance to infection by HIV. The lab identifies ~30 new A-T patients, worldwide, per year, and has characterized the majority of the ~500 unique ATM mutations ( Individual ongoing projects are now trying to characterize drugs that correct the expression of full length, functional ATM protein in cells with nonsense-type mutations and in others that have splicing mutations. These involve high throughput screening of 10,000s of chemicals, as well as collaborations with pharma companies and with the NIH for Neurological Diseases and Stroke (NINDS) on other compounds. This lab has the largest repository of cell lines from A-T patients, an important resource for these ongoing studies. Recent publications include: Lange et al. Localization of an ataxia-telangiectasia gene to a ~500 kb interval on chromosome 11q23.1: linkage analysis of 176 families in an international consortium. Amer J Hum Genet 57: 112-119, 1995. Savitsky et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268: 1749-1753, 1995. [Accompanying Research News article by R. Nowak: Discovery of AT gene sparks biomedical research bonanza. Science 268: 1700-1701, 1995.] Pan-Hammarstrom et al. ATM is not required in somatic hypermutation of VH, but is involved in the introduction of mutations in the switch u region. J. Immunol. 170:3707-3716, 2003 Lai et al. Correction of ATM gene function by aminoglycoside-induced readthrough of premature termination codons. Proc Natl Acad Sci.101: 15676-81, 2004. Birrell et al. ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia. Hum Mutation 25: 593m 2005. Nahas et al. Post-irradiation phosphorylation of structural maintenance chromosome 1 (SMC1) is independent of the Fanconi protein pathway. Intl J Rad Oncol Biol. Physics 61: 1167-72, 2005. Cavalieri et al. ATM mutations in Italian families with ataxia-telangiectasia include two distinct large genomic deletiions. Hum Mutation 27:1061-71, 2006 Du L, Pollard J, Gatti RA. Correction of prototypic ATM splicing mutation and aberrant ATM function with antisense morpholino oligonucleotides. PNAS 104: 6007-6012, 2007.