Sandra Citi is a cell biologist and academic. She discovered the protein cingulin in the 1980s. Her work and research interests focus on the molecular mechanisms underlying the function of epithelial cell junctions and their connection to the cytoskeleton, including studies on proteins such as cingulin, paracingulin, ZO-1, and PLEKHA7.
Education
Citi completed her Bachelor of Science in Biological Sciences from the University of Florence in 1982. She was trained in the Structural Studies Division of the MRC Laboratory of Molecular Biology in Cambridge, UK, where she received a Ph.D. in 1986. After completing her Ph.D., she carried out postdoctoral work at the Weizmann Institute of Science in 1987. In 1989, she earned a M.D. degree from the University of Florence.
Career
Citi began her academic career in 1989 as an assistant professor of Cell Biology and Anatomy at Cornell University Medical College, New York, a position she held until 1993. She moved to the University of Padova, Italy, in 1994, where she worked as an assistant professor until 2009. Between 1996 and 2025, she was a principal investigator and associate professor in the Department of Molecular and Cellular Biology at the University of Geneva. She received independent funding from the Swiss National Science Foundation.
Research
Citi's research has focused on the molecular organization, function, and regulation of epithelial junctions. Her work has particularly focused on the protein cingulin, which she discovered in the 1980s, highlighting its structural functions in tethering nonmuscle myosins-2 to tight junctions and its role in regulating the expression of tight junction proteins during epithelial differentiation. She also investigated paracingulin (CGNL1), demonstrating its involvement in linking microtubules to tight junctions through CAMSAP3, and examined its significance in the regulation of GEFs and GAPs. She showed that kinase signaling regulates cadherin-mediated adhesion by modulating cytoskeletal contractility. She also conducted studies on the expression, localization, and phosphorylation of tight junction proteins.
Citi has also studied how molecular interactions and mechanical forces influence junctional components, showing that tension induces conformational changes in the major tight junction scaffolding protein Tight junction protein ZO-1 (TJP1), leading to nuclear signaling events that regulate cell proliferation and barrier function. She also reported that tight junctions act not only as barriers but also as dynamic signaling platforms and are involved in mechanotransduction to regulate apical cortex mechanics. Her work also clarified to the role of PLEKHA proteins in the trafficking and function of the copper pump ATP7A and in host-pathogen interactions. Additionally, her work has also linked alterations in junctional proteins such as Claudin-1 and PLEKHA7 to cancer progression, observing their reduced expression in lung and breast carcinomas.
Citi, S; Sabanay, H; Jakes, R; Geiger, B; Kendrick-Jones, J (1988-05-19). "Cingulin, a new peripheral component of tight junctions". Nature. 333 (6170): 272–276. Bibcode:1988Natur.333..272C. doi:10.1038/333272a0. PMID3285223.
Spadaro, Domenica; Le, Shimin; Laroche, Thierry; Mean, Isabelle; Jond, Lionel; Yan, Jie; Citi, Sandra (2017). "Tension-Dependent Stretching Activates ZO-1 to Control the Junctional Localization of Its Interactors". Current Biology. 27 (24): 3783–3795.e8. Bibcode:2017CBio...27E3783S. doi:10.1016/j.cub.2017.11.014. PMID29199076.
Shah, Jimit; Rouaud, Florian; Guerrera, Diego; Vasileva, Ekaterina; Popov, Lauren M; Kelley, William L; Rubinstein, Eric; Carette, Jan E; Amieva, Manuel R; Citi, Sandra (2018). "A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote α-Toxin Cytotoxicity". Cell Reports. 25 (8): 2132–2147.e7. doi:10.1016/j.celrep.2018.10.088. PMID30463011.
↑Zhu, Guang-Jie; Huang, Yuhang (2023). "Cingulin regulates hair cell cuticular plate morphology and is required for hearing in human and mouse". EMBO Molecular Medicine. 15 (11): 2. doi:10.15252/emmm.202317611– via PubMed.
↑Higashi, Tomohito; Saito, Akira C.; Chiba, Hideki (2024). "Damage control of epithelial barrier function in dynamic environments". European Journal of Cell Biology. 103 (2): 2. doi:10.1016/j.ejcb.2024.151410. PMID38579602.
↑Troyanovsky, R. B.; Klingelhöfer, Jörg; Troyanovsky, Sergey (1999). "Removal of calcium ions triggers a novel type of intercadherin interaction". Journal of Cell Science. 112 (23): 4384. doi:10.1242/jcs.112.23.4379. PMID10564655– via PubMed.
↑Rathman, M.; de Lanerolle, P.; Ohayon, H.; Gounon, P.; Sansonetti, P. (2000). "Myosin light chain kinase plays an essential role in S. flexneri dissemination". Journal of Cell Science. 113 (Pt 19): 3376. doi:10.1242/jcs.113.19.3375. PMID10984429.
↑Danilchik, Michael V; Bedrick, Steven D; Brown, Elizabeth E; Ray, Kimberly (2003). "Furrow microtubules and localized exocytosis in cleaving Xenopus laevis embryos". Journal of Cell Science. 116 (Pt 2): 281. doi:10.1242/jcs.00217. PMID12482913.
↑Eckert, Judith J.; Fleming, Tom P. (2008). "Tight junction biogenesis during early development". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1778 (3): 721. doi:10.1016/j.bbamem.2007.09.031. PMID18339299.
↑Smales, Caroline; Ellis, Moira; Baumber, Rachel; Hussain, Nayer; Desmond, Howard; Staddon, James M. (2003). "Occludin phosphorylation: identification of an occludin kinase in brain and cell extracts as CK2". FEBS Letters. 545 (2–3): 161–166. Bibcode:2003FEBSL.545..161S. doi:10.1016/s0014-5793(03)00525-8. PMID12804768.
↑Rosenbaum, David; Saftig, Paul (2024). "New insights into the function and pathophysiology of the ectodomain sheddase A Disintegrin And Metalloproteinase 10 (ADAM10)". FEBS Journal. 291 (13): 2751. doi:10.1111/febs.16870. PMID37218105.
12Chao, Yu-Chih; Pan, Szu-Hua; Yang, Shuenn-Chen; Yu, Sung-Liang; Che, Ting-Fang; Lin, Chung-Wu; Tsai, Mu-Shiun; Chang, Gee-Chen; Wu, Che-Hsiang; Wu, Yi-Ying; Lee, Yung-Chie; Hong, Tse-Ming; Yang, Pan-Chyr (15 January 2009). "Claudin-1 Is a Metastasis Suppressor and Correlates with Clinical Outcome in Lung Adenocarcinoma". American Journal of Respiratory and Critical Care Medicine. 179 (2): 124. doi:10.1164/rccm.200803-456OC. ISSN1073-449X. PMID18787218.
12Jeung, Hei-Cheul; Puentes, Roisin; Aleshin, Alexander; Indarte, Martin; Correa, Ricardo G.; Bankston, Laurie A.; Layng, Fabiana I. A. L.; Ahmed, Zamal; Wistuba, Ignacio; Yao, Yong; Duenas, Daniela G.; Zhang, Shuxing; Meuillet, Emmanuelle J.; Marassi, Francesca; Liddington, Robert C.; Kirkpatrick, Lynn; Powis, Garth (2021). "PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer". Experimental Cell Research. 409 (2): 2. doi:10.1016/j.yexcr.2021.112930. ISSN0014-4827. PMID34800542.