Zhiyong Xi

###Education
B.S., 1991, Biopharmaceutics, China Pharmaceutical University
Ph.D., 2005, Medical Entomology, University of Kentucky
Postdoctoral Fellow, 2005-2007, Molecular Microbiology and Immunology, Johns Hopkins University

###Research
Both the distribution range of mosquito vectors and the prevalence of mosquito-borne diseases have rapidly increased because of global warming in recent decades. A highly effective, sustainable, and environmentally friendly vector control strategy is urgently needed because of the insufficiency of traditional approaches. Recently, significant efforts have been made to develop Wolbachia-based approaches to either reduce the mosquito’s ability to transmit pathogens through population replacement or to suppress the mosquito density below the epidemic risk threshold through population suppression. Successful field trials have shown that Wolbachia-based population replacement has reduced dengue incidence by 77.1% and hospitalization by 86.2% in [Indonesia](https://www.nejm.org/doi/full/10.1056/NEJMoa2030243), among several other countries, and population suppression has been shown to produce strong suppression or even [elimination](https://www.nature.com/articles/s41586-019-1407-9) of Aedes mosquito vectors in target areas in multiple countries, with dengue incidence being reduced by up to 71.01% in [Singapore](https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(23)00397-X/fulltext). 

Estimated to infect more than half of all insect species, [Wolbachia](https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(21)00134-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312821001347%3Fshowall%3Dtrue) is a maternally transmitted endosymbiotic bacterium belonging to the order Rickettsiales. It is known for its ability to induce cytoplasmic incompatibility (CI), a phenomenon involving early embryonic death that occurs when the Wolbachia-infected male mates with either an uninfected female or a female carrying a different strain of Wolbachia. Based on CI, a conditional sterility can be induced in the field by releasing the incompatible males to mate with naturally uninfected wild-type females, resulting in population suppression. CI also provides a reproductive advantage to Wolbachia-infected females as compared to uninfected females, since infected females can produce infected offspring after mating with both infected and uninfected males, whereas uninfected females can reproduce only if they mate with uninfected males. With Wolbachia frequencies surpassing a critical equilibrium determined by fitness costs, CI would facilitate the invasion and spread of Wolbachia into uninfected populations and eventually causes the population infected at high frequency, triggering population replacement.

The pillars of a Wolbachia-based disease control strategy include maternal transmission, CI, pathogen blocking, and fitness, all of which can be affected by the external environmental factors mosquitoes encounter in the field and [genetic backgrounds](https://academic.oup.com/pnasnexus/article/1/4/pgac203/6711710) of both mosquito hosts and their transmitted human pathogens. Our long-term goal is to develop Wolbachia-based strategies to control arboviruses, including dengue virus transmitted by Aedes mosquitoes, and malaria transmitted by Anopheles mosquitoes. To achieve this, we will identify factors that enable Wolbachia-based population replacement and suppression to succeed in a manner that controls disease transmission sustainably and cost-effectively. Specifically, we are interested in:

* Developing stable artificial symbiosis between mosquitoes (Aedes, Anopheles, and Culex) and Wolbachia (supergroups A and B), with focuses on exploring the mechanisms underlying novel [symbiosis formation](https://www.nature.com/articles/ismej2017174) and characterizing their profiles for use in disease control according to [WHO standards](https://cdn.who.int/media/docs/default-source/ntds/vector-ecology-mangement/tpp-wolbachia-infected-aedes-aegypti-population-replacement-intervention.pdf?sfvrsn=5296c1dc_3);
* Understanding the molecular mechanism of Wolbachia-mediated [pathogen blocking](https://www.pnas.org/doi/abs/10.1073/pnas.1116932108) in mosquitoes, including suppression of Plasmodium in Anopheles and dengue virus in Aedes;
* Developing effective mosquito [sex separation](https://www.science.org/doi/10.1126/scirobotics.adj6261) system for mass production of Wolbachia-infected males for field release;
* Developing the next-generation improved Wolbachia-based mosquito population replacement and suppression for [disease control at scale](https://divportal.usaid.gov/s/project/a0g3d000000cNZAAA2/testing-a-combined-sitiit-approach-to-control-mosquitoborne-diseases-at-scale?utm_medium=email&utm_source=govdelivery).

As a pioneer and global leader in establishing novel Wolbachia symbiosis, we are the first in the world to successfully establish stable artificial Wolbachia infections in mosquito vectors of dengue ([Aedes aegypti](https://www.science.org/doi/10.1126/science.1117607) and Aedes albopictus) and malaria ([Anopheles stephensi](https://www.science.org/doi/10.1126/science.1236192)), as well as in [hemipteran insects](https://www.cell.com/current-biology/fulltext/S0960-9822(20)31364-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982220313646%3Fshowall%3Dtrue). This technique, often referred to as [transinfection](https://link.springer.com/protocol/10.1007/978-1-0716-3553-7_11), aims to generate a stable, maternally inherited Wolbachia infection—essentially forcing the formation of a novel symbiosis between Wolbachia and mosquito hosts—by using embryonic microinjection to introduce Wolbachia into the germ plasm of early recipient embryos. We (or MSU) have recently been granted a new patent, allowing us to further lead the field of transinfection with efforts to identify the best Wolbachia strain for disease control in regions with specific environmental or ecological conditions, particularly in challenging hosts like Anopheles mosquitoes. Our lab features a state-of-the-art insectary and a BSL-2 facility, enabling us to work on the dengue virus in both mosquito and cell cultures. Additionally, we have strong expertise in functional genomic assays, including RNA interference and mosquito gene editing using CRISPR/Cas9. Over the last ten years, we have also made significant efforts in conducting field trials to develop Wolbachia for dengue control in [China](https://www.nature.com/articles/s41586-019-1407-9) and [Mexico](https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010324).