Li-av Segev-Zarko's research interests lie in understanding host-pathogen interactions at the molecular level, with a particular focus on membranes in the context of pathogenesis. As a graduate student in the lab of Prof. Yechiel Shai at the Weizmann Institute of Science, she investigated the involvement of host-derived antimicrobial peptides (AMPs) in biofilm prevention and discovered new mechanisms by which AMPs can reduce biofilm formation and degrade existing biofilms. During her postdoc with Prof. John Boothroyd at Stanford University, Dr. Segev-Zarko shifted her focus to a eukaryotic system to study how apicomplexan parasites interact with host cell membranes during invasion. In her work, she developed workflows integrating state-of-the-art imaging techniques, including cryogenic electron tomography (cryo-ET), to study the invasion machinery of Toxoplasma gondii and Plasmodium falciparum. By resolving the 3D organization of the invasion machinery of Toxoplasma gondii in its native cellular context, she revealed an evolutionarily conserved feature and provided new insights into its role during the initial steps of invasion.

These discoveries have formed the basis for her current research lab at UTMB. Dr. Segev-Zarko joined the Department of Biochemistry and Molecular Biology and the Sealy Center for Structural Biology and Molecular Biophysics in 2024.

The phylum Apicomplexa includes several of the most prevalent and important human eukaryotic pathogens. For example, Plasmodium spp. cause malaria, resulting in the deaths of over 600000 individuals in 2021, with 80% being children under the age of 5. Cryptosporidium spp. are a leading global cause of diarrheal burden in children under the age of 5, and Toxoplasma gondii causes toxoplasmosis, especially in immunocompromised patients. To enter a host cell, these parasites utilize a specialized structure at their anterior end called the apical complex (AC), and consists of cytoskeleton elements and specialized secretory organelles. The exact means by which the various components of the AC coordinate invasion have been a mystery due, in part, to a lack of tools capable of resolving the structure of this extraordinary apparatus in its natural context. To address this, we couple cryogenic electron tomography with molecular and biochemical tools to study the invasion machinery of Toxoplasma gondii.

The Segev-Zarko lab studies the identity, structure, and function of parasite and host cell proteins involved in the invasion and manipulation of the host cell. They are particularly focused on studying novel eukaryotic secretion mechanisms that are essential for the close association between parasite and host cell membranes, which is necessary for successful infection.

Segev-Zarko L., Dahlberg P.D., Sun S.Y., Pelt D., Kim C.Y., Egan E.S., Sethian J.A., ChiuW., Boothroyd J.C. Cryo-electron tomography with mixed-scale dense neural networks reveals key steps in deployment of Toxoplasma invasion machinery. PNAS-Nexus (2022) Volume 1, Issue 4.

Sun S.Y.*, Segev-Zarko L.*, Chen M.*, Pintilie G.D., Schmid M.F., Ludtke S.J., Boothroyd J.C., Chiu W. (*equal contribution). Cryo-ET of Toxoplasma parasites gives subnanometer insight into tubulin based structures. Proc. Natl. Acad. Sci. U.S.A. (2022) 119(6):e2111661119.

Sun S.Y.*, Segev-Zarko L.*, Pintilie G.D., Kim C.Y., Staggers S.R., Schmid M.F., Egan E.S., Chiu W., Boothroyd J.C. (*equal contribution). Cryogenic electron tomography reveals novel structures in the apical complex of Plasmodium falciparum. mBio. 2024 Apr 10;15(4):e0286423.