具有增殖能力和分化多能性的生发细胞是泡球蚴在宿主体内持续生长发育的基础。我们研究发现：宿主EGF可通过激活泡球蚴EGFR信号通路，促进生发细胞增殖/自我更新和泡球蚴生长发育，同时G1/S期关键分子Cyclin D显著上调；抑制EGFR/ERK信号通路则下调Cyclin D、E，生发细胞增殖和泡球蚴生长发育受到抑制，推测相关信号通路通过调控生发细胞周期继而影响泡球蚴生长发育。本项目为验证假说，拟开展：分析泡球蚴生发细胞周期调控特点；研究宿主EGF对生发细胞周期的影响；阐明EGFR-ERK-Cyclin D-CDK4/6、Cyclin E-CDK2信号通路在泡球蚴生长发育中的作用机制以及宿主因子的影响；动物实验探索靶向CDK激酶的小分子药物对宿主体内泡球蚴生长发育的影响。本项目从宿主因子影响生发细胞周期调控这一新角度出发，对泡球蚴生长发育的分子机理展开研究，亦有助于发现泡球蚴病的新药物靶标。

Germinative cells, a population of cells that are totipotent and capable of extensively proliferating, are essential for the continuous larval growth and development of Echinococcus multilocularis in human. In our previous study, we found that host EGF can activate the EGFR signaling in the parasite and promote the proliferation/self-renewal of germinative cells and larval growth. Meanwhile, the transcriptional level of Cyclin D, a key regulator of G1/S phase, was significantly upregualted. We also found downregulated Cyclin D/E and impaired germinative cell proliferation and larval growth upon the inhibition of the parasite’s EGFR/ERK signaling. These results are suggestive of relevant cell-cycle-regulating signaling pathways involved in controlling the behaviors of germinative cells and the larval growth and development of E. multilocularis. In this project, we will study the mechanisms regulating the cell cycle of germinative cells in E. multilocularis. We will elucidate the role of EGFR-ERK-Cyclin D-CDK4/6 and Cyclin E-CDK2 signaling pathways in regulating larval development of the parasite as well as the influence of host EGF. We will also investigate in vivo the effects of CDK inhibitors on the development of the parasite in host using the animal model. This research will offer a new sight to study the mechanisms regulating the larval growth and development of E. multilocularis, and will be helpful in discovering new drug targets for the treatment of alveolar echinococcosis.