The goal of the Citi laboratory is to understand how specific proteins of the junctional complex of vertebrate epithelial and endothelial cells contribute to physiology and pathology at the molecular, cellular, tissue, organ and organism levels.

Epithelial and endothelial tissues play a fundamental role in in separating different body compartments, and in the absorption, secretion and barrier functions of major organs. The vast majority of cancers arises within epithelial organs, and invasion and metastasis correlate with disruption or loss of cell-cell junctions. Epithelia are also the first target of pathogens. Endothelial cells play a fundamental role in cardiovascular physiology.

We are specifically interested in clarifying how specific protein components of epithelial tight and adherens junctions interact with the cytoskeleton to regulate cell architecture, mechanics of the membrane cortex, signaling and different aspects of epithelial cell and tissue function (barrier, adhesion, pathogen interaction, electrolyte physiology, etc.). We are also interested in how mechanical force affects protein conformation and interactions, and how connections of junctions to the actomyosin cytoskeleton determines the mechanical properties of the plasma membrane cortex. We discovered in 2017 that ZO-1 is a mechanosensing protein; in 2022 that cingulin interaction with ZO-1 regulates ZO-1 conformation; in 2023 that cingulin and paracingulin tethering to the actomyosin cytoskeleton regulates apical membrane cortex stiffness, tight junction membrane tortuosity and adherens junction organization; in 2025 that gamma-actin also regulates apical membrane cortex stiffness.

We use a combination of biochemical, cellular and in vivo approaches, including the generation and characterization of knockout mice, which help us to frame the significance of our discoveries within the context of a whole vertebrate organism.

Please browse the Research and Publications pages for more details of our work!