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>Miguel Rovira, researcher at IRB Barcelona</p>
30 Jul 2018

TV3's "Telenotícies" programme interviewed Miguel Rovira, a PhD student at IRB Barcelona and the first author of a recent study published in the journal EMBO Molecular Medicine.

<p>Manuel Serrano, group leader of the Cellular Plasticity and Disease laboratory at IRB Barcelona.</p>
27 Jul 2018

El Punt Avui, Al Día, Noticias de la Ciencia, Catalunya Press, among other media, have published an article about a study led by Manuel Serrano, leader of the Laboratory of Cellular Plasticity and

<p>The figure shows two views, frontal and lateral, of the image obtained by CT of the lungs of a mouse with fibrosis (grey areas) before and after receiving nano-therapy directed at senescent cells. (Guillem Garaulet and Francisca Mulero, CNIO)</p>
26 Jul 2018

Senescent cells are damaged cells that do not perform their normal roles anymore but that are not dead –hence they are commonly known as zombi cells.

<p>Image: BIST</p>
27 Jun 2018

Gabby Silberman, director general of the Barcelona Institute of Science and Technology, took advantage of his speech welcoming the more than 300 researchers participating in the BIST annual

Upcoming events

04 Oct
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Andre Nussenzweig, Ph.D. NIH Distinguished Investigator. Center for Cancer Research National Cancer Institute. Bethesda, Maryland (US)
05 Oct
Aula Fèlix Serratosa, Parc Científic de Barcelona
15 Nov
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Louis Vermeulen MD, PhD. Center for Experimental and Molecular Medicine, Academic Medical Center. Amsterdam. The Netherlands