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>Roger Gomis, head of the Growth Control and Cancer Metastasis Lab</p>
27 Jun 2018

Gabby Silberman, director general del Barcelona Institute of Science and Technology, ha aprovechado su discurso de bienvenida a los más de 300 investigadores participantes en la conferencia

<p>Manuel Serrano, head of the Cellular Plasticity and Disease laboratory at IRB Barcelona</p>
26 Jun 2018

El programa “30 Minuts” de TV3, ha publicado un reportaje que plantea si será posible alargar la vida más allá de los límites actuales, ralentizando o deteniendo el envejecimiento como si fuera una

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

El próximo miércoles 27 de junio más de 300 líderes de investigación se reunirán en CosmoCaixa para debatir los últimos avances científicos en ámbitos punteros —energía, salud, medio ambiente— de g

<p>Image: El País</p>
15 Jun 2018

El diario El País ha publicado un artículo sobre la aplicación de la técnica CRISPR en células humanas, que podría fomentar la aparición de tumores, según dos artículos publicados en la revista Nat

Upcoming events

27 Jul
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Evripidis Gavathiotis, PhD – Associate Professor – Department of Biochemistry – Department of Medicine – Center for Experimental Therapeutics Albert Einstein Cancer Research – Wilf Family Cardiovascular Research Institute – Institute of Aging Research – N