John E. French, PhD
John E. “Jef” French, PhD, joined the Nutrition Research Institute as a Visiting Professor of Nutrition for the 2017-2018 academic year.
Areas of Research Interest
His research interests focus on identifying the gene x environment interactions (including nutrients) and the underlying mechanisms that aid explanation of inter-individual differences in susceptibility and resistance to disease. Current NRI collaborative research projects in development using new genetically-diverse mouse models include the genetics of increased risk for basal-like breast cancer associated with obesity and resistance to carboplatin chemotherapy (Stephen Hursting Lab) and the genetics of maternal-fetal alcohol toxicity and the potential for dietary intervention (Susan Smith Lab).
Previously, Dr. French led The Host Susceptibility Initiative (HSI) at the National Toxicology Program, National Institute of Environmental Health Sciences, in Research Triangle Park. In this research, he used both haplotype diversity panels of inbred mice and Diversity Outbred mice to investigate inter-individual differences resulting from chemical stressor induced toxicity and disease. The HSI collaborated on the sequencing of 15 homozygous inbred strains for comparison to the C57BL/6 sequence. Analysis of the DNA sequence of these strains by several labs, including UNC-CH, showed that the laboratory mice used in contemporary research are not as genetically diverse as originally understood. Although more than 8 million new SNPs were identified along with significant identity by descent with no SNP variants for haplotype-phenotype association studies. Indirectly, this data increased support for the creation of the Collaborative Cross recombinant inbred lines (CC RIL) to support quantitative genetic research in biology and medicine. In addition, this work provided incentive for the Sanger Institute to deep sequence 18 inbred mouse strains, including the founders of the CC RIL. Multiple investigators from the Complex Traits Community had pursued an eight-way multiple advanced generation intercross to increase genetic diversity that supported mouse population genetics research. The CC RIL and the Diversity Outbred mice, which were derived by completely random mating of a large founding population of early CC RIL, provide powerful and complementary tools for quantitative genetics research. Genetic diversity in the CC RIL or DO mice approximate that in ethnic human populations (~45 millions single nucleotide polymorphisms and structural variants), but they have a much higher minor allele frequency (~12%) compared to human populations that significantly increases the power of genotype-phenotype association using smaller population samples. These mouse populations have the potential to identify risk variants of significant effect size in an experimental model with potential outcomes for translation to human biology and medicine.
Education and Professional Accomplishments
Dr. French received his PhD from North Carolina State University at Raleigh in Comparative Biochemistry and Molecular Toxicology under Ernest Hodgson and John Roberts. He was a postdoctoral trainee in radiation biology at the NIH-NNMC in Bethesda, Maryland) where he investigated ionizing radiation toxicity and suppression of immune and xenobiotic metabolism systems in multiple model organisms. Tenured at the NIH-FDA as a Supervisory Research Physiologist, he led a research group and served as a scientific reviewer for New Drug Applications using biological therapeutics. Later, he was recruited to the NIEHS-NTP in Research Triangle Park, NC, where he served as research scientist and project officer for toxicology and carcinogenesis studies and investigate the effects of caloric restriction and dietary antioxidants on growth hormone and IGF1 axis mechanisms in the suppression of cancer in genetically-engineered mouse models. He received an NIH-USPHS fellowship to research loss of heterozygosity and cancer susceptibility genes in human lung cancers related to asbestos and smoking exposures under the Nordic Ministries Cancer Research Initiative at the Finnish Institute of Occupational Health in Helsinki, Finland and the Swedish Institute of Occupational Health in Stockholm Returning to the NIEHS, Dr. French led the Transgenic Carcinogenesis Group (Laboratory of Environmental Carcinogenesis and Mutagenesis and Laboratory of Molecular Toxicology, NIEHS) and used genetically altered mouse models (Trp53, Hras, etc.) to investigate chemical and ionizing radiation mutagenesis and carcinogenesis. Dr. French also led the Host Susceptibility initiative for the NTP/NIEHS. Research was focused on the development and use of population based animal models to investigate chemical and ionizing radiation toxicity and cancer phenotypes. Currently, he is a NIH Special Volunteer and serves as Adjunct Professor in the Center for Pharmacogenetics and Individualized Therapy in the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill. He has co-authored more that 150 peer-reviewed research publications and published technical reports.