ABSTRACTParasites of the genera Plasmodium and Toxoplasma represent a substantial source of often-deadly global human parasitic infections. Toxoplasma gondii infects over two billion people worldwide, resulting in life-long chronic infection, and has a profound impact on host health, and manifests in disease primarily in immunocompromised individuals. An exceptional and important aspect of this protozoan is its widespread ability to infect any nucleated warmed-blooded animal. The life cycle of the parasite in a host causes rounds of host cell lysis, resulting in tissue damage. Sequential discharge of micronemes, rhoptries and dense granules, which form a unique triad of secretory endomembranes, contributes to the extraordinarily successfulness of this parasite to invade and propagate within its infected cells. Upon and after cell invasion, Toxoplasma releases a myriad of host modulating effectors to promote its survival and dissemination. Of the many host-manipulating proteins, the dense granules effectors (GRAs) are responsible for structural modification of the parasitophorous vacuole in which the parasite develops within the cell. Several GRAs have also been identified as controlling multiple host cell biological processes, including manipulation of signaling events, alteration of host transcription, apoptosis, immune function, and the cell cycle program. This dissertation explores how T. gondii manipulates the host cell cycle to force its genome replication. We characterized a GRA effector HCE1 by determining its role in the induction of the host cell cycle via the upregulation of Cyclin E to stimulate G1/S-phase transition and reveal a block in S-phase progression and DNA synthesis in the host. Moreover, we demonstrated that this S-phase block was dependent on the host cell. Notably, we illustrated that removal of host cell contact inhibition promotes DNA synthesis and this S-phase block was dependent on the host cell background. These data offer the first evidence of a T. gondii effector capable of modulating host cell cycle phases and answers a long-standing question in the field of Toxoplasma biology in manipulating its infected host. This dissertation also examines other aspect of Toxoplasma biology, including our investigation of the roles of Secretory Effector Binding protein 1 (SEB1), an essential Golgi-resident protein, in parasite survival and replication.