• Education:

2010.9–2015.6: Institute of Plant Physiology and Ecology, CAS, Zoology, PhD

2006.9–2010.7: Shannxi Normal University, Biological Sciences, Bachelor

• Working experience:

2026.3-Present: CAS Center for Excellence in Molecular Plant Sciences, Investigator

2025.6- Present: Scripps Research Institute, Staff Scientist

2024.7–2025.6: University of California, San Diego，Staff Research Associate III

2018.7–2024.6: University of California, San Diego, Postdoctoral Fellow

2015.6–2018.6: Institute of Plant Physiology and Ecology, CAS, Assistant Professor

Gene-drive is a promissing strategy for genetic control of insect populations. By targeting specific genomic loci to induce DNA double-strand breaks and trigger cellular homologous recombination repair, it enables the preferential spread and Super-Mendelian inheritance of target genes within populations.

Gene-drive overcomes the technical bottlenecks of traditional population genetic control, including low efficiency and the requirement for large-scale release of transgenic individuals, providing an innovative approach for the efficient management of insect pests. However, significant differences exist among mosquito species in reproductive and developmental patterns, genome size and structure, which directly affect DNA homologous recombination repair and lead to substantial variations in gene-drive efficiency: 95% in Anopheles mosquitoes, 80% in Aedes mosquitoes, and falls below 70% in Culex mosquitoes.

Our main research intends to use Aedes albopictus, which transmits the widest variety of viruses and poses the most severe public health threat in China, as the research model, to elucidate the molecular mechanisms underlying the low efficiency of gene-drive in Aedes mosquitoes, and then develop novel, high efficient and precise gene-drive systems for Aedes, providing new insights and techniques for combating mosquito-borne viruses.

Our research interests focus on understanding of “Double-stranded Breaks (DSBs) repair mechanism in somatic cells” and “Using gene-drive strategy to combat malaria transmission in Anopheles mosquitoes”. The detailed research achievements are as follows:

We developed a CopyCatcher system in Drosophila to detect and quantify homology-directed recombination (HDR) events in somatic cells. Our study demonstrated that HDR efficiency in Drosophila somatic cells exceeds 30%, significantly higher than the efficiency in mammalian cells (<10%). By combining CopyCatcher with RNA interference (RNAi) technology, we conducted a small-scale in vivo genetic screening in Drosophila, identifying several conserved key factors involved in homologous recombination. These findings were further validated in mammalian cells through collaboration with Professor Stephen M. Hedrick’s lab, at the University of California, San Diego. The discovery of these key somatic DSB repair factors could be potentially used for improving the efficiency of CRISPR/Cas9-mediated gene therapy. Additionally, CopyCatcher represents an innovative and efficient platform for studying somatic cell HDR repair pathways. The work was published in Nature Communications (2021).

Secondly, we developed the ICP (Integrated Classifier Pipeline), a bioinformatics tool designed to investigate somatic DSB repair mechanism using Drosophila as a model organism. By integrating next-generation sequencing (NGS) with computational analysis, ICP enables precise characterization of CRISPR/Cas9 editing outcomes at the allelic level. The pipeline visualizes editing products as mutant fingerprints, categorizing alleles based on reads ratio and mutation types. Using this approach, we discovered that DSB repair pathways usage dynamically shifts during insect development, revealing new insights into the regulation of somatic DNA repair. ICP provides a novel platform for high-throughput analysis of gene editing outcomes and repair mechanisms in vivo. This work was published in Nature Communications (2024).

Building on the foundational research into insect somatic DSB repair mechanism, we optimized gene drive technology in Anopheles stephensi and developed a novel population replacement gene drive system, linked allelic-drive. This system successfully propagated a naturally occurring point mutation that confers broad malaria parasite-infection resistance, throughout the mosquito population and effectively blocked the parasite transmission within mosquitoes. This innovative approach represents a transformative paradigm for safer and more efficient population-level vector control and has been published in Nature (2025).

First Author Publications:

1. Li, Z.#, Dong, Y.#, You, L., Corder, M.R., Arzobal, J., Yeun, A., Yang, L., Marshall, M.J., Dimopoulos, G., Bier, E.* (2025) Driving a protective allele of the mosquito FREP1 gene to combat malaria. Nature. 645(8081): 746-754.

2. Li Z., You L., Hermann A., Bier E.* (2024) Developmental progression of DNA double strand break repair deciphered by a single-allele resolution mutation classifier. Nat. Commun. 15(1): 2629.

3. Li, Z., You, L., Zhang, Q., Yu, Y., Tan, A.* (2022) A targeted in-fusion expression system for recombinant protein production in Bombyx mori. Front. Genet. 4: 12.

4. Li, Z., Nimi, M., Devkota, S., Auradkar, A., Hedrick, M.S., Gantz, M.V., Bier, E.* (2021) CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion. Nat. Commun. 2(1): 2625.

5. You, L., Zhang, F., Huang, S., Merchant, A., Zhou, X.*, Li, Z.* (2020) Over-expressing of RNA interference (RNAi) core machinery improves susceptibility to RNAi in silkworm larvae. Insect Mol. Biol. 29(4): 353-362.

6. You, L., Bi, H., Wang, Y., Li, X., Chen, X., Li, Z.* (2019) CRISPR/Cas9-based mutation reveals Argonaute1 is essential for pigmentation in Ostrinia furnacalis. Insect Sci. 26(6): 1020-1028.

7. Li, Z., You, L., Y, Dong, James, A.A., Huang, Y., Tan, A.* (2018) Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination. PLoS Genet. 14(2): e1007245.

8. Li, Z., You, L., Zeng, B., Ling, L., Xu, J., Huang, Y.*, Tan, A.* (2015) Ectopic over-expression of ecdysone oxidase disrupted larval-pupal transition in Bombyx mori. Proc. Biol. Sci. 282(1809).

9. Li, Z., Zeng, B., Ling, L., Xu, J., You, L., Aslam, A., Tan, A.*, Huang, Y.* (2014) Enhancement of larval RNAi efficiency by over-expressing the Argonaute2 in Bombyx mori. Int. J. Biol. Sci. 11(2): 176-185.

10. Li, Z., Zeng, B., Ling, L., Xu, J., You, L., Aslam, A., Huang, Y.*, Tan, A.* (2014) CYP18A1 regulates tissue-specific steroid hormone inactivation in Bombyx mori, Insect Biochem. Mol. Biol. 54C: 33-41.

11. Li, Z., Jiang, J., Chen, Y., You, L., Niu, B., Meng, Z., Huang, Y., Tan, A.* (2014) PDP1 regulates energy metabolism through the IIS-TOR pathway in the red flour beetle, Tribolium castaneum. Arch. Insect. Biochem. Physiol. 85(3): 127-136.

Co-author Publications:

1. Lima, L., Berni, M., Mota, J., Bressan, D., Julio, A., Cavalcante, R., Macias, V., Li, Z., Rasgon, J., Bier, E., Araujo, H.* (2024) Gene editing in the chagas disease vector Rhodnius prolixus by Cas9-mediated ReMOT control. CRISPR J. 7(2): 88-89.

2. Terradas, G., Bennett, J., Li, Z., Mashall, M.J., Bier, E.* (2023) Genetic conversion of a split-drive into a full-drive element. Nat. Commun. 14(1): 191.

3. Roy, S., Juste, S., Sneider, M., Auradkar, A., Klanseck, C., Li, Z., Julio, A., Lopez, V., Bier, E., Guichard, A.* (2022) Cas9/Nickase-induced allelic conversion by homologous chromosome-templated repair in Drosophila somatic cells. Sci. Adv. 8(26): eabo0721.

4. You, L., Li, Z., Zhang, Z., Hu, B., Yu, Y., Yang, F., Tan, A.* (2022) Two dehydroecdysone reductases act as fat body-specific 20E catalyzers in Bombyx mori. Insect Sci. 29(1).

5. Liu, Z., Li, Z., Shang, P., Huang, Y., Tan, A.* (2019). Effects of the space environment on silkworm development time. In: Duan, E., Long, M. (eds) Life Science in Space: Experiments on Board the SJ-10 Recoverable Satellite. Research for Development. Springer, Singapore.

6. Xu, J., Zhan, S., Chen, S., Zeng, B., Li, Z., James, A.A., Tan, A., Huang, Y.* (2017) Sexually dimorphic traits in the silkworm, Bombyx mori, are regulated by doublesex. Insect Biochem. Mol. Biol. 80: 42-51.

7. Zeng, B., Zhan, S., Wang, Y., Huang, Y., Xu, J., Liu, Q., Li, Z., Huang, Y., Tan, A.* (2016) Expansion of CRISPR targeting sites in Bombyx mori. Insect Biochem. Mol. Biol. 72: 31-40.

8. Ling, L., Ge, X., Li, Z., Zeng, B., Xu, J., Chen, X., Shang, P., James, AA., Huang, Y.*, Tan, A.* (2015) MiR-2 family targets awd and fng to regulate wing morphogenesis in Bombyx mori. RNA Biol. 12(7): 742-748.

9. Xu, J., Bi, H., Chen, R., Aslam, AFM., Li, Z., Ling, L., Zeng, B., Huang, Y., Tan, A.* (2015) Transgenic characterization of two testis-specific promoters in the silkworm, Bombyx mori. Insect Mol. Biol. 24(2): 183-190.

10. Xu, J., Wang, Y., Li, Z., Ling, L., Zeng, B., James, AA., Tan, A.*, Huang, Y.* (2014) Transcription activator-like effector nuclease (TALEN)-mediated female-specific sterility in the silkworm, Bombyx mori. Insect Mol. Biol. 23(6): 800-807.

11. Wang, Y., Tan, A., Xu, J., Li, Z., Zeng, B., You, L., Chen, Y., James, AA.*, Huang, Y.*, (2014) Sit-specific, TALENs-mediated transformation of Bombyx mori. Insect Biochem. Mol. Biol. 55: 26-30.

12. Chen, Y., Li, M., Islam, I., You, L., Wang, Y., Li, Z., Ling, L., Zeng, B., Xu, J., Huang, Y., Tan, A.* (2014) Allelic-specific expression in relation to Bombyx mori resistance to Bt toxin. Insect Biochem. Mol. Biol. 54: 53-60.

13. Xu, J., Wang, Y., Li, Z., Ling, L., Zeng, B., You, L., Chen, Y., slam, AFM., Huang, Y., Tan, A.* (2014) Functional characterization of the vitellogenin promoter in the silkworm, Bombyx mori. Insect Mol. Biol. 23(5): 550-557.

14. Ling, L., Ge, X., Li, Z., Zeng, B., Xu, J., Aslam, AFM., Song, Q., Shang, P., Huang, Y.*, Tan, A.*, (2014) MicroRNA Let-7 regulates molting and metamorphosis in the silkworm, Bombyx mori. Insect Biochem. Mol. Biol. 53: 13-21.

15. Wang, Y., Li, Z., Xu, J., Zeng, B., Ling, L., You, L., Chen, Y., Huang, Y.*, Tan, A.* (2013) The CRISPR/Cas system mediates efficient genome engineering in Bombyx mori. Cell Research. 23(12): 1414-1416.

16. Tan, A., Fu, G., Jin, L., Guo, Q., Li, Z., Niu, B., Meng, Z., Neil, I.M., Luke, A., Huang, Y.* (2013) Transgene-based, female-specific lethality system forgenetic sexing of the silkworm, Bombyx mori. PNAS. 4: 12.

17. Jiang, J., Ge, X., Li, Z., Wang, Y., Song, Q., Stanley, WD., Tan, A.*, Huang, Y.* (2013) MicroRNA-281 regutaltes the expression of ecdysone receptor (EcR) isform B in the silkworm, Bombyx mori. Insect Biochem. Mol. Biol. 43(8): 692-700.

18. Ge, X., Zhang, Y., Jiang, J., Zhong, Y., Yang, X., Li, Z., Huang, Y., Tan, A.* (2012) Identification of microRNAs in Helicoverpa armigera and Spodoptera litura based on deep sequencing and homology analysis. Insect Biochem. Mol. Biol. 9(1), 1.

19. Zhao, Y., Zhang, H., Li, Z., Duan, J., Jiang, J., Wang, Y., Zhan, S., Akinkurolere RO., Xu， _A., Qian, H., Miao, X., Tan, A., Huang, Y. * (2012) A major faclitator superfamily protein participates in the reddish brown pigmentation in Bombyx mori. J. Insect Physiol. 58(11): 1397-1405.