Molecular MedicineCellular Plasticity and Disease

Cellular Plasticity and Disease
Group Leader

ICREA Research Professor, ERC Advanced Grant, "la Caixa" Foundation

+34 93 40 20287
Joint appointment: Oncology

The unifying concept that has guided our research over the years is that tumor suppressor genes protect from many types of damage regardless of the particular detrimental consequences of the damage. In other words, tumor suppressors protect from damage even if that damage is not going to produce cancer, but a degenerative disease. According to this view, cancer protection is just one of the outcomes of tumor suppressors, being other outcomes protection from chronic diseases, from nutritional overload, from tissue injuries, or from aging.

Tumor suppressors often trigger a stereotypic cellular state known as cellular senescence, and our group has made seminal contributions to the understanding of cellular senescence from a physiological perspective.

During the last 5 years, we have made key contributions to the advance of our understanding of tumor suppression, damage, cellular senescence and tissue regeneration:

  1. The primary function of cellular senescence is to orchestrate tissue regeneration (Cell 2013; Science 2016).
  2. Tumor suppressors protect from aging (Cell Metab. 2012) and from the damage caused by nutritional overload, including obesity and metabolic syndrome (Cell Metab. 2015).
  3. Tumor suppressors regulate cell plasticity (Nature 2009; Cell Stem Cell 2012).
  4. Cell plasticity can be induced and manipulated in vivo (Nature 2013).

The key emerging paradigm is that tumor suppressors, by triggering cellular senescence, recruit inflammatory cells and create a tissue microenvironment that favors tissue repair and regeneration.

We are dissecting the molecular mechanisms and we are applying this knowledge to the treatment of various diseases, including pulmonary fibrosis and cancer.

1. Tissue regeneration in the reprogrammable mice.
We are actively studying tissue regeneration in our reprogrammable mice (where we can induce the four Yamanaka factors in vivo) and how this is affected by tissue injury, senescence and inflammation.

2. Therapeutic effects of elimination of pathological senescent cells.
We have a very original project on the use of silica nanoparticles to deliver drugs selectively into senescent cells. We are focused on their therapeutic potential in pulmonary fibrosis.

3. Manipulating and understanding pluripotency.
We have several projects aimed to manipulate and stabilize pluripotency with chemical compounds, both in mouse and in human cells. For example, we can hyperactivate the Mediator complex with a chemical compound and in this manner we can stabilize the naïve state of pluripotency in mouse and human cells. We are attempting to deliver reprogramming chemicals in vivo to enhance tissue regeneration.

4. Targeting pluripotency in cancer.
We have a strong line of research on cancer and in this regard we have identified new chemical compounds that selectively target cancer stem cells.

5. Understanding aging.
We have several projects aimed to understand the connection between metabolic pathways, tumor suppressors and aging.

Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R.M., Chondronasiou, D., Rovira, M., Fernández-Marcos, P.J., Muñoz-Martin, M., Blanco-Aparicio, C., Pastor, J., Gómez-López, G., de Martino, A., Blasco, M.A., Abad, M. and Serrano, M.
Science, 6315 (354), -pii: aaf4445 (2016)
Ortega-Molina, A., Lopez-Guadamillas, E., Mattison, J.A., Mitchell, S.J., Muñoz-Martin, M., Iglesias, G., Gutierrez, V.M., Vaughan, K.L., Szarowicz, M.D., González- García, I., López, M., Cebrián, D., Martinez, S., Pastor, J., de Cabo, R. and Serrano, M.
Cell Metab., (21), 570-558 (2015)
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M. and Serrano, M.
Cell, 1104 (21), -1118 (2013)
Abad, M., Mosteiro, L., Pantoja, C., Cañamero, M., Rayon, T., Ors, I., Graña, O., Megías, D., Domínguez, O., Martínez, D., Manzanares, M., Ortega, S. and Serrano, M.
Nature, (502), 345-340 (2013)
Ortega-Molina, A., Efeyan, A., Lopez-Guadamillas, E., Muñoz-Martin, M., Gomez, G., Cañamero, M., Mulero, F., Pastor, J., Martinez, S., Romanos, E., Gonzalez-Barroso, M.M., Rial, E., Valverde, A.M., Bischoff, J.R. and Serrano, M.
Cell Metab., (15), 394-382 (2012)
Li, H., Collado, M., Villasante, A., Matheu, A., Lynch, C.J., Cañamero, M., Rizzoti, K., Carneiro, C., Martínez, G., Vidal, A., Lovell-Badge, R. and Serrano, M.
Cell Stem Cell, (7), 852-845 (2012)
Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M.A. and Serrano, M.
Nature, (460), 1139-1136 (2009)

  • ERC Advanced Grant (European Research Council)
  • Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation)
  • "la Caixa" Foundation

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Group news & mentions

<p>Manuel Serrano Lab</p>
19 Gen 2018

La regulació del activitat de l'ARN polimerasa II, que catalitza la transcripció de l'ADN per generar ARN missatgers, és central en la diferenciació cel·lular i el manteniment de la identitat cel·l

<p>Manuel Serrano, group leader of the Cellular Plasticity and Disease laboratory at IRB Barcelona.</p>
22 Des 2017

La Vanguardia, La Razón, Diari Médico, entre altres mitjans, han destacat el reconeixement a

<p>Manuel Serrano, group leader of the Cellular Plasticity and Disease laboratory at IRB Barcelona.</p>
20 Des 2017

El cap del laboratori de Plasticitat Cel·lular i Malaltia de l’Institut de Recerca Biomèdica (IRB Barcelona) i professor d'Investigació d'ICREA, Manuel Serrano, ha estat guardonat amb el XVII Premi

30 Oct 2017

Diario Médico explica, a través de la investigadora de l’IRB Barcelona Cristina Pantoja, la feina que es du a terme en medicina regenerativa al laboratori Plasticitat Cel·lular i Malaltia.

Upcoming events

24 Gen
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Dr Travis Johnson, Lecturer, Head - Drosophila developmental biology group, Faculty of Science School of Biological Sciences, Australia
26 Gen
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Alejandra Bruna, PhD Associate Scientist Cancer Research UK Cambridge Institute University of Cambridge
31 Gen
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Marta Shahbazi, Postdoctoral Fellow Department of Physiology, Development and Neuroscience, University of Cambridge, UK