The females of most mosquito species require blood from vertebrate animals to produce their eggs. During the blood feeding, mosquitoes transmit many devastating diseases, such as malaria, dengue fever, filariasis and West Nile encephalitis. Mosquito population control is crucial to reduce the incidence of infection and transmission of disease. It is of great importance to study regulation of gene expression in mosquito development and reproduction to identify accessible targets that can be exploited to prevent mosquito-vectored disease transmission.
My research interest lies in elucidating the juvenile hormone signaling pathway in mosquitoes. This insect hormone affects a remarkably diverse array of processes in mosquito development and life history, including metamorphosis, reproduction, behavior, diapause, stress resistance and longevity. However, the molecular action of juvenile hormone remains poorly understood. We have recently discovered a key transcriptional regulatory complex that activates the expression of juvenile hormone target genes. This is a major contribution to our understanding of juvenile hormone action at the molecular level. One of the transcriptional activator, the methoprene-tolerant (Met) protein, binds juvenile hormone with high affinity. We are working with Dr. Bevan’s lab to use molecular modeling and structurally driven mutagenesis to characterize the hormone binding pocket in Met. In addition, we are investigating how this regulatory complex is recruited to the juvenile hormone-inducible promoters. This study is expected to provide a framework for understanding the juvenile hormone actions in the mosquito, which in turn may lead to the development of new mosquito pesticides that specifically block the normal functions of juvenile hormone.
My laboratory is also interested in signal transduction and gene regulation in mosquitoes in general, aiming at bridging genomics and proteomics. Rapid progress in mosquito genomics has allowed us to study transcriptome changes in many biological events. At the same time, accumulating evidences demonstrate that expression of many mosquito genes is regulated at the post-transcriptional level. We are working together with colleagues in this department to use genome-wide polysome profiling to assess the translational status of individual mRNA transcripts. This method has led to identification of over 500 genes that are translationally up-regulated when female mosquitoes become infected by malaria parasites. The results from this study will advance our knowledge of the interactions between anopheline mosquitoes and malaria parasites, and reveal genetic factors that determine the ability of the mosquitoes to transmit the parasites.

Li, M., Mead, E.A., and Zhu, J. (2011) Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene expression. Proc. Natl. Acad. Sci. U.S.A. 108: 638-643.

Zhu, J., Busche, J. M., and Zhang, X. (2010) Identification of juvenile hormone target genes in the adult female mosquitoes. Insect Biochem Mol Biol 40: 23-29.

Bian, G., Raikhel, A. S., and Zhu, J. (2008) Characterization of a juvenile hormone-regulated chymotrypsin-like serine protease gene in Aedes aegypti mosquito. Insect Biochem Mol Biol 38: 190-200.

Shiao, S., Hansen, I. A., Zhu, J., Sieglaff, D. H., and Raikhel, A. S. (2008) Juvenile hormone connects larval nutrition with target of rapamycin signaling in the mosquito Aedes aegypti. J Insect Physiol 54: 231-239.

Nene et al. (2007) Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316:1718-23. (95 co-authors).

Zhu, J., Chen, L., and Raikhel A.S. (2007) Distinct roles of Broad isoforms in regulation of the 20-hydroxyecdysone effector gene, Vitellogenin, in the mosquito Aedes aegypti. Mol Cell Endocrinol 267: 97-105.

Zhu, J., Chen, L., Sun, G, and Raikhel A.S. (2006) The competence factor FTZ-F1 directs stage-specific ecdysteroid-induced gene expression. Mol Cell Biol 26: 9402-9412.

Sun, G., J. Zhu, L. Chen, & A.S. Raikhel (2005) Synergistic action of E74B and ecdysteroid receptor in activating a 20-hydroxyecdysone effector gene. Proc. Natl. Acad. Sci. USA. 102:15506-11.

Chen, L., J. Zhu, G. Sun, & A.S. Raikhel (2004) The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti. J. Mol. Endocrinol. 33:743-61.

Sun, G., J. Zhu, & A.S. Raikhel (2004) The early gene E74B isoform is a transcriptional activator of the ecdysteroid regulatory hierarchy in mosquito vitellogenesis. Mol. Cell. Endocrinol. 218:95-105.