Conferencia
Senescencia celular en el desarrollo, la regeneración tisular y el cáncer
Manuel Collado, PhD
Instituto de Investigación Sanitaria (IDIS)
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela, España
Día y hora - CAMBIO POR MEDIDAS GREMIALES
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Viernes 29 de setiembre de 2023
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10:00 horas
Lugar
- Anfiteatro Maggiolo, Facultad de Medicina
Invita
Centro de Investigaciones Biomédicas, Facultad de Medicina
Scientific contributions
Our laboratory was created officially in June 2012 when I was awarded a Miguel Servet, although laboratory space was not available until February 2013. Since then, we have worked to establish a group within the Health Research Institute of Santiago de Compostela, IDIS, whose main scientific focus has been to advance our knowledge of the cellular senescence process in general, and specifically to improve cancer treatment. In the last 10 years we have published 36 papers and book chapters.
During these years we have advanced our knowledge on the process of cellular senescence to expand the range of settings in which this response plays crucial roles. For example, we identified developmentally-induced senescence as a crucial morphogenetic player during embryogenesis, an observation that we also made in lower vertebrates such as fish, showing that this process is evolutionarily conserved. We also identified senescence contributing to tissue repair and regeneration using zebrafish and demonstrated how the transient induction of senescence favors tissue regeneration.
In cancer, we showed that inflammation can contribute to pancreatic cancer development by inhibiting oncogene-induced senescence and identified the Cardiac glycosides as a new family of broad spectrum senolytic compounds. This discovery provides a new set of senolytics, reveals vulnerabilities of senescent cells, and proves the “one-two punch” strategy against cancer based on the combination of pro-senogenic chemotherapy and senolytics.
We have also worked on cellular reprogramming and used it to deepen our knowledge of the plasticity associated with oncogenic transformation. In this sense, we identified a previously unrecognized tumor suppression activity for cell cycle regulators p27Kip1 and the retinoblastoma family related with the transcriptional repression of pluripotency gene Sox2. We also observed how the activation of oncogenic Ras results in signaling promoting dedifferentiation, measured as enhanced reprogramming to pluripotency. This might be one of the key elements in the transforming activity of this oncogene. Finally, we demonstrated how the exhaustion of adult stem cell populations leads to cellular senescence and premature aging as demonstrated by using a mouse model of conditional depletion of Sox2+ cells.
We have also contributed review articles by invitation to recapitulate our current knowledge of senescence in development, repair and regeneration, and senolytics, as well as a key review in the field setting the standards of definition, description, markers, function, etc, of cellular senescence (published in Cell).
We have published 75 articles, receiving close to 120 citations per item on average, h-index 32.
I am part of the International Cell Senescence Association (ICSA) steering committee and organized their second conference in Santiago de Compostela in July 2015. I created the Cellular senescence coordinated group of the SEBBM. I am part of the Spanish Network in Cellular Senescence and organized our latest meeting in Santiago in November 2021. I am frequently invited to review articles for top journals (Nature Communications, Nature Aging, Nature Cancer, Nature Metabolism, Nature Cell Biology, Cancer Cell, Aging Cell, PNAS, etc), and grants and contracts from international funding agencies from Israel, France, UK, The Netherlands, Belgium, Czech Rep, Switzerland, etc.
