Robert Schiestl, PhDProfessor, Departments of Pathology and Laboratory Medicine, Environmental Health Sciences, Radiation Oncology, Jonsson Comprehensive Cancer Center, UCLA
Robert H. Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being professor at Harvard at the age of 31 where he stayed for 10 years. Since 15 years he is professor at UCLA with 187 publications, 10 patents and 2 startup companies.
Intestinal microbiota plays a role in the nutrient metabolism, modulation of the immune system, arthritis, obesity and intestinal inflammation. In the literature there have been huge differences in the same Atm deficient mice in different labs reported. When our lab moved from Harvard to UCLA we found a similar difference in genetic instability and logevity. When we changed the intestinal microbiota back to conventional microbiota we could reproduce the phenotype at Harvard. We tested Atm deficient mice for genotoxicity, genetic instability, DNA damage, inflammation markers, cancer latency and longevity and high throughput sequencing of the intestinal microbiota. Isogenic mice from different housing facilities showed a four fold difference in life expectancy, a 4.5 fold difference in genetic instability and DNA damage. The onset of lymphomas was significantly 2 fold different. We sequenced the microbiota of both facilities and found Lactobacillus johnsonii 456 as dominant bacterial strain in the health beneficial microbiota. Just this bacterium by itself reduced genotoxicity, reduced inflammation and reduced levels of cytotoxic T cells in the liver and blood. We also found similar differences in Trp53 deficient and even in wildtype mice. The underlying mechanisms is probably due to inflammation promotion or suppression mediated by the intestinal microbiota. The understanding of this effect may lead to a breakthrough in the understanding of the causes of carcinogenesis, which might lead to prevention of AT, a currently incurable progressive disease and possibly other cancer-prone DNA repair deficient diseases or even wildtype mice and people.
Relevant Recent Publications
- Yamamoto, L. I. Maier , A. T. Dang , D. Berry , J. Liu, P. M. Ruegger , J. Yang, P. A. Soto, L. L. Presley, R. Reliene , A. M. Westbrook , B. Wei , A. Loy , C.r Chang , J. Braun , J. Borneman, R. H. Schiestl (2013) Intestinal bacteria modify lymphoma penetrance in genetically susceptible mice via inflammation-mediated systemic host oxidative stress and leucocyte genotoxicity- Cancer Research 73(14):4222-4232 July 15, 2013 PMCID: PMC3718495
- Westbrook, A. and R.H. Schiestl (2010) Atm deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation. Cancer Research 70, 1875, March 1, 2010. PMCID: PMC2831166