Bronchioalveolar cellular and molecular hierarchy in homeostasis and disease
Juan-Jose Ventura Juan started his PhD studies in Molecular Biology at the University Complutense of Madrid focusinghis work on the role of inflammatory signals in liver development. Following his interest in MAPKs, he moves to Roger Davis group at the HHMI/UmassMed school in Worcester, MA. After that period, Juan moved back to Madrid with a Ramon y Cajal contract to work at the CNIO with Angel Nebreda. In this group, they uncover a novel role for the p38a/MAPK in lung homeostasis and cancer. Juanâ€™s growing interest in this topic led him to become a PI and start his own group at the newly established CSCR in the University of Cambridge. He has been trying to study the insights of lung bronchioalveolar regulation since then.
The Ventura lab is interested in deciphering the ways used by the lung to replenish its damaged tissue in normal conditions and how that can go wrong in disease, and especially in lung cancer. Using animal models and human samples we are trying to determine the existence of specific groups of cells with a potential to differentiate and regenerate any other cell types that can have died, allowing the maintenance of lung functionality. Defining molecules that specifically can be targeted for distinct populations will allow the tracking, isolation, study and potential use as cellular therapy to regenerate damaged areas. Knowing the intracellular mechanisms involved in regulating when those progenitors should differentiate and into what cell type will be essential to understand the process of regeneration and any possible used in the clinic. We have uncovered some molecular targets that target progenitor populations with diverse differentiation potential and mechanisms involved in maintaining the proper process of regeneration. Failure of the mechanisms regulating these cell populations results in lung diseases as lung fibrosis or cancer. Combining in vivo experiments with the optimization of lab methods we are increasing our knowledge on lung physiology and the possibility to manipulate it to combat disease.
Lineage tracing of Lrig1 cells after bronchiolar injury
Funding MRC CRUK EMBO Herchel-Smith
Key Publications F. Oeztuerk-Winder, A. Guinot, A. Ochalek and J-J. Ventura. Corresponding author..Regulation of Human Lung Alveolar multipotent cells by a novel p38a MAPK/miR-17-92 axis. EMBO J. 2012 Jul 24;31(16):3431-41. doi: 10.1038/emboj.2012.192. Epub 2012 Jul 24. PMID::22828869 F. Oeztuerk-Winder and J-J. Ventura. Corresponding author. The many faces of p38 mitogen-activated protein kinase in progenitor/ stem cell differentiation. REVIEW. Biochem J. 445(2012), 1-10. PMID: 22702973
J-J. Ventura, S. Tenbaum, E. Perdiguero, C. Guerra, M. Barbacid, M. Pasparakis, and AR. Nebreda. Corresponding author Essential role of p38Îą MAP kinase in lung stem/progenitor cell proliferation and differentiation: implications for tumorigenesis Nat Genetics. 39 (2007). 750-58. Epub 2007 Apr 29. DOI.10.1038/ng2037. PMID: 17468755
Feride Oeztuerk-Winder Anna Guinot Josue Ruiz Medina