Andrei Ivanov, PhD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Dr. Ivanov’s research interests are focused on fundamental mechanisms that regulate cell-cell adhesions and epithelial barriers under normal homeostatic conditions and mechanisms controlling disruption and recovery of epithelial barriers during inflammation, infection and tumor progression.
Tissue and organ development is critically regulated by intercellular adhesion proteins which control the assembly of biological barriers, establishment of cell polarity and differentiation, as well as orchestrated movement of cell clusters during tissue morphogenesis and repair. These adhesion proteins cluster into elaborate cell-cell adhesion complexes called junctions whose dynamic assembly, maintenance and disassembly is controlled by a plethora of exogenous and endogenous signaling factors. In turn, cell-cell junctions act as versatile environmental sensors and signal transducers that ignite a variety of intracellular molecular and signaling pathways. Disassembly of cell-cell junctions results in the disruption of epithelial and endothelial barriers during tissue inflammation and dissemination of cancer cells during tumor metastasis.
Dr. Ivanov’s laboratory explores molecular mechanisms that regulate disruption and recovery of most known epithelial adherence and tight junctions during inflammatory diseases and cancer. Furthermore, we are interested in mechanisms by which epithelial junctions control collective cell migration. We are particularly interested in roles of the actin cytoskeleton, myosin motors, septin cytoskeleton and vesicular trafficking machinery in delivering, retaining and removal of different adherens and tight junctional components at the cell-cell adhesion sites. We use a variety of experimental systems including model epithelial cell monolayers treated with different inflammatory and tumor-promoting agents, in vivo models of intestinal inflammation and colitis-associated colon cancer, as well as tissue biopsies from patients with inflammatory bowel diseases and colon cancer. We examine integrity and permeability of epithelial junctions and cell migration by using various, imaging, functional and biochemical approaches.
From the translational perspectives, our work is aimed at developing novel strategies to prevent breakdown of epithelial barriers and accelerate their recovery in different diseases states. These strategies can be used to develop new therapeutic approaches to attenuate tissue inflammation and tumor metastasis.
Research will explore the complex roles of cytoskeletal motors in regulating gut epithelila interaction with bacterial pathogens to develop new defensive therapeutics.
Dr. Ivanov and his team have clarified the essential protective role of Β-actin in regulating the epithelial barrier and intestinal inflammation.