Michael Schnoor PhD

Full Professor Cinvestav 3D
SNI: Level 3
PhD in Biochemistry (2004), University of Münster, Germany
Office: +52 (55) 5747-3321
Lab: +52 (55) 57473800 ext-5026

Website

 

Summary

The inflammatory response is a crucial element of survival. Inflammation protects the body from invading pathogens and is the first step of regeneration and wound healing after injury. All inflammatory responses start with the extravasation of leukocytes from the blood stream into affected tissues. Inflammation is also often accompanied by increased vascular permeability. These processes need to be tightly regulated, because if not controlled properly, a continuous inflammatory response can lead to tissue damage and chronic inflammatory diseases. Thus, elucidating the molecular mechanisms that control vascular permeability and leukocyte extravasation is of utmost importance for understanding why and when an acute inflammation turns into a chronic inflammation. Although much effort has been spent on elucidating the molecular mechanisms regulating vascular permeability and leukocyte extravasation in inflammatory diseases, many details are still poorly understood. While several adhesion molecules play a key role in mediating endothelial cell contact stability and leukocyte transmigration, much less is known about the role of actin, actin-binding molecules and related intracellular signaling.

We are investigating mechanisms of inflammation regulated by actin-binding proteins in vitro using cell culture systems and in vivo using genetically manipulated mice. To this end, we apply state-of-the-art methodology including intravital microscopy, confocal microscopy, multi-panel flow cytometry, permeability assays, and xenotransplantations, among others. We utilize experimental disease models including DSS colitis, CLP-sepsis, leukemic xenotransplantations, and cremaster inflammation.

We have shown that the endothelial actin-binding protein cortactin regulates vascular permeability and neutrophil extravasation in vivo by distinct molecular mechanisms including activation of small GTPases such as Rap1 and RhoG, and clustering of key endothelial adhesion molecules for leukocytes such as ICAM-1.

Cortactin also regulates intestinal epithelial permeability and leukocyte recruitment into the intestinal mucosa by controlling epithelial actomyosin contractility. Cortactin deficient mice are more susceptible to experimental colitis and individuals suffering from IBD show reduced cortactin levels.

Importantly, we could also show that cortactin is overexpressed in children with acute lymphoblastic leukemia, and that high levels of cortactin in leukemic B cells are related to increased risks of organ infiltration and disease relapse.

Using these approaches, we are also examining the role of other actin-binding proteins such as HS1, myosin-1e, adducin and WIP in leukocyte extravasation and tissue barrier regulation.

Currently, we are also trying to identify new treatment approaches for severe Covid-19 using a model of lung inflammation in pre-clinical studies.

(full list: https://pubmed.ncbi.nlm.nih.gov/?term=schnoor+m&sort=date)

  • Valle-Reyes, S., Dobrovinskaya, O., Pelayo, R. Schnoor, M. Acute lymphoblastic leukemia cell lines in immunology research. Trends in Immunology, 2021, epub ahead of print, doi: 10.1016/j.it.2020.12.007.

  • Schnoor, M., Vadillo, E., Guerrero-Fonseca, I.M. The extravasation cascade revisited from a neutrophil perspective. Current Opinion in Physiology, 2021, epub ahead of print. https://doi.org/10.1016/j.cophys.2020.09.014

  • Stahnke, S., Döring, H., Kusch, C., de Gorter, D.J.J., Dütting, S., Guledani, A., Pleines, I., Schnoor, M., Sixt, M., Geffers, R., Rohde, M., Müsken, M., Kage, F., Steffen, A., Faix, J., Nieswandt, B., Rottner, K., Stradal, T.E.B. Loss of Hem1 disrupts macrophage function and impacts on migration, phagocytosis and integrin-mediated adhesion. Current Biology, 2021, Mar 6:S0960-9822(21)00287-6. doi: 10.1016/j.cub.2021.02.043, epub ahead of print.

  • Castellanos-Martínez, R., Jiménez-Camacho, K.E., Schnoor, M. Cortactin expression in the hematopoietic system: implications for hematological malignancies. American Journal of Pathology, 2020, 190, 5, 958-967. ISSN print: 00029440; ISSN online: 15252191.

  • Vadillo, E., Chánez-Paredes, S., Vargas-Robles, H., Guerrero-Fonseca, I.M., Castellanos-Martínez, R., García-Ponce, A., Nava, P., Girón-Pérez, D.A., Santos-Argumedo, L., Schnoor, M. Intermittent rolling is a new defect of the extravasation cascade caused by Myosin1e-deficiency in neutrophils. Proceedings of the National Academy of Science USA, 2019, 116, 52, 26752-26758. pii: 201902502. doi: 10.1073/pnas.1902502116. ISSN print: 00278424; ISSN online: 10916490

  • Velázquez-Avila, M., Balandrán, J.C., Ramírez, D., Velázquez-Avila, M., Sandoval, A., Felipe-López, A., Nava, P., Alvarado-Moreno, J.A., Dozal, D., Prieto-Chávez, J.L., Schaks, M., Rottner, K., Dorantes-Acosta, E., López-Martínez, B., Schnoor, M.*, Pelayo, R*. High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse. Leukemia, 2019, 33, 6, 1337-1348. doi: 10.1038/s41375-018-0333-4. *shared senior and corresponding authorship. ISSN print: 08876924; ISSN online: 14765551

  • Castro Ochoa, K.F., Vargas Robles, H., Chánez-Paredes, S., Felipe-López, A., Cabrera-Silva, R.I., Shibayama, M., Betanzos, A., Nava, P., Galinski, E.A., Schnoor M. Homoectoine protects against colitis by preventing a claudin switch in epithelial tight junctions. Digestive Diseases and Sciences, 2019, 64, 2, 409-420. doi: 10.1007/s10620-018-5309-8. Epub 2018 Sep 29. ISSN print: 01632116; ISSN online: 15732568

  • Schnoor, M., Stradal, T.E., Rottner, K. Cortactin: cell functions of a multi-faceted actin-binding protein. Trends in Cell Biology, 2018, 28, 2, 79-98. doi: 10.1016/j.tcb.2017.10.009. ISSN print: 09628924; ISSN online: 18793088

  • Vadillo, E., Dorantes-Acosta, Pelayo, R., Schnoor, M. T cell acute lymphoblastic leukemia (T-ALL): new insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies. Blood Reviews, 2018, 32, 1, 36-51. doi: 10.1016/j.blre.2017.08.006. ISSN print: 0268960X; ISSN online: 15321681

  • Citalán-Madrid, A.F., Vargas-Robles, H., García-Ponce, A., Shibayama, M., Betanzos, A., Nava, P., Salinas Lara, C., Rottner, K., Mennigen, R., Schnoor, M. Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction and disproportionately severe DSS-induced colitis. Mucosal Immunology, 2017, 10, 5, 1237-1247. doi: 10.1038/mi.2016.136. ISSN print: 19330219; ISSN online: 19353456

  • Latasiewicz, J., Artz, A., Jing, D., Pacheco-Blanco, M., Currie, S.M., Velázquez Avila, M., Schnoor, M.,* Vestweber, D.* HS1 deficiency impairs neutrophil recruitment in vivo and activation of the small GTPases Rac1 and Rap1. Journal of Leukocyte Biology, 2017, 101, 5, 1133-1142, doi:10.1189/jlb.1A0416-195R, *shared corresponding authorship. ISSN print: 07415400; ISSN online: 19383673

  • García-Ponce, A., Citalán-Madrid, A.F., Vargas-Robles, H., Chánez-Paredes, S., Nava, P., Betanzos, A., Zarbock, A., Rottner, K., Vestweber, D. Schnoor, M. Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility. Scientific Reports, 2016, 6, srep29003, doi:10.1018/srep29003. ISSN print: N/A; ISSN online: 20452322

  • Schnoor, M. Alcaide, P., Voisin, M.B., van Buul, J.D. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation. Mediators of Inflammation, vol. 2015, Article ID 946509, 23 pages, 2015. doi:10.1155/2015/9465092015.

  • Schnoor, M., Lai, F.P.L., Zarbock, A., Kläver, R., Polaschegg, C., Schulte, D., Weich, H.A., Oelkers, J.M., Rottner, K., Vestweber, D. Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo. Journal of Experimental Medicine, 208, 8, 2011,1721-1735.

  • Schnoor, M., Betanzos, A., Weber, D. A., Parkos, C. A. Guanylate binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-? and regulates barrier function through effects on apoptosis. Mucosal Immunology, 2, 1, 2009, 33-42.