Research interests

1. De novo mutations occur not only in tumor cells but also in normal somatic cells. Although mutations in tumors are easily identifiable because most of them are clonally expanded, mutations in normal cells are usually unique to each individual cell and not distinguishable from technical errors when sequencing a bulk cell population. Dr. Zhang and her colleagues in the Vijg lab developed a novel in vitro single-cell DNA amplification method of high enough fidelity to accurately determine unique mutations from the whole genome of a single cell at single base pair level.

2. DNA mutations as a consequence of errors during DNA damage repair, replication or mitosis/meiosis are the substrate for evolution. People can estimate genome maintenance accuracy through the measurement of DNA mutations. Genome maintenance has long been implicated in the evolution of species-specific maximum life span and aging. Dr. Zhang applied the new single-cell sequencing method that she developed to study somatic mutations in humans during aging and in different species with diverse life spans. She found that somatic mutations accumulate in human B cells during aging and that these mutations are deleterious in functional genomic regions. And She discovered that mouse has a significantly higher mutation frequency than human. These results provided the first evidence that the accumulation of somatic mutations can be a causal factor in aging and a determinant of diverse life spans.

Publications

1. Zhang L* Dong X* Lee M, Maslov AY, Wang T, Vijg J. Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan. Proceedings of the National Academy of Sciences. 2019; 116 (18), 9014-901(*Co-first author)

2. Zhang L and Vijg J. Somatic mutagenesis in mammals and its implications for human disease and aging. Annual Review of Genetics. 2018 Nov 23; 52:397-419

3. Dong X, Zhang L*, Milholland B, Lee M, Maslov AY, Wang T, Vijg J. Accurate and reliable identification of single nucleotide variants in whole genome-amplified single cells. Nature Methods. 2017; 14: 491-493 (*Co-first author)

4. Vijg J, Dong X, and Zhang L. A high-fidelity method for genomic sequencing of single somatic cells reveals a very high mutational burden. Exp Bio Med. 2017; 242(13):1318-1324

5. Milholland B, Dong X, Zhang L*, Hao X, Suh Y, Vijg J. Profound differences between germline and somatic mutation rates in humans and mice. Nature Communications. 2017; 8 15183 (*Co-first author)

6. Vijg J, Dong X, Milholland B and Zhang L. Genome instability: a conserved mechanism of aging? Essays Biochem. 2017 May 26. pii: EBC20160082

7. Nie XQ, Yang B, Zhang L, Gu Y, Jiang WH, Yang S and Yang C. PTS regulation domain-containing transcriptional activator CelR and sigma factor σ54 control cellobiose utilization in Clostridium acetobutylicum. Molecular Microbiology. 2016 100(2):289-302

8. Zhang L, Nie XQ, Gu Y, Jiang WH, and Yang C. Redox-responsive repressor Rex modulates alcohol production and oxidative stress tolerance in Clostridium acetobutylicum. Journal of Bacteriology. 2014 196(22):3949-3963

9. Zhang L, Leyn SA, Gu Y, Jiang WH, Rodionov DA, and Yang C. Ribulokinase and Transcriptional Regulation of Arabinose Metabolism in Clostridium acetobutylicum. Journal of Bacteriology. 2012 194(5):1055-1064

10. Liu LX, Zhang L*, Tang W, Gu Y, Hua Q, Yang S, Jiang WH, and Yang C. Phosphoketolase Pathway for Xylose Catabolism in Clostridium acetobutylicumRevealed by 13C Metabolic Flux Analysis. Journal of Bacteriology, 2012 194(19):5413-5422, (*Co-first author)

11. Gu Y, Li j, Zhang L, Chen J, Niu LX, Yang YL, Yang S, Jiang WH. Improvement of xylose utilization in Clostridium acetobutylicumvia expression of the talA gene encoding transaldolase from Escherichia coli. Journal of Biotechnology. 143(2009), 284-287, 2009

12. L Zhang, X Dong, M Lee, AY Maslov, T Wang, J Vijg. Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan
    Proceedings of the National Academy of Sciences 116 (18), 9014-9019