Manuel Serrano

Manuel Serrano

Institut de Recerca Biomèdica de Barcelona

Life & Medical Sciences

Manuel Serrano obtained his PhD in 1991 for his research at the Centre for Molecular Biology (CSIC/UAM, Madrid)) under the supervision of M. Salas and J.M. Hermoso. From 1992 to 1996 he worked as a Postdoctoral Fellow in the laboratory of D. Beach at the Cold Spring Harbor Laboratory, New York, USA. In 1997, he returned to Spain to start his own research group at the Spanish National Biotechnology Centre (CSIC, Madrid). He moved to the Spanish National Cancer Research Centre (Madrid) in 2003 to lead the Tumour Suppression Group, where he also served as Director of the Molecular Oncology Programme (2012-2017). In May 2017, he relocated to the Institute for Biomedical Research-IRB Barcelona to establish the Cellular Plasticity and Disease Group within the Molecular Medicine Research Programme. He has accomplished important scientific contributions to the understanding of Ageing from different perspectives: Cancer & Ageing, Metabolism & Ageing, Regeneration & Ageing.

Research interests

The unifying concept that has guided our research is that tumour suppressors protect the organism from many types of damage, regardless of the pathology that a given damage may cause. Protection from cancer is just one of the outcomes of tumour suppressors, others being protection from chronic diseases, nutritional overload, tissue injuries, or aging. Tumour suppressors often trigger a cellular state known as cellular senescence, and we have pioneer the concept that cellular senescence is critical to signal tissue damage and to elicit tissue regeneration. The key emerging paradigm is that tumour suppressors, by triggering cellular senescence, recruit inflammatory cells and create a tissue microenvironment that favours tissue repair and regeneration. Damage → Tumour Suppressors → Cellular Senescence → (secreted factors) → Cellular Plasticity → Tissue Repair

We are now focused on two major areas of research:

- Cellular plasticity: this is a property that many cells have intrinsically (this is the case of stem/progentor cells and many cancer cells) but it is also a property that can be acquired upon injury or damage (this is the case of facultative progenitor cells).  We are interested in two concepts: induction of plasticity using as a tool the Yamanaka factors (Oct4, Sox2, Klf4 and Myc); and reduction of plasticity using as a tool our recently reported "agonist of enhancers" (an inhibitor of CDK8 that potentiates MEDIATOR).

- Cellular senescence:  we are trying to understand the mechanisms underlying this response, the mechanisms of survival, the particular metabolic adaptations of these cells, non-invasive methods for their detection in vivo, their interplay with the immune system, and strategies to trigger the elimination of long-term resident (pathological) senescent cells.

Our overarching goal is to understand and manipulate tissue repair and regeneration.

Selected publications

- Salazar-Roa M ...//... Serrano M ...//... & Malumbres M. 2020, 'Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells', Embo Journal, 39, e104324.  

- Lynch CJ ...//... Serrano M. 2020, 'Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases', Nature Cell Biology, 22, 1223-1238.

- Lynch CJ, Bernad R, Calvo I & Serrano M 2020, 'Manipulating the Mediator complex to induce naive pluripotency', Experimental Cell Research, 395, 112215.

- Rodriguez-Matellan A, Alcazar N, Hernandez F, Serrano M & Avila J 2020, 'In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice', Stem Cell Reports, 15, 1056 - 1066.  

- Gonzalez-Gualda E ...//... Serrano M, Doherty GJ, Martinez-Mañez R & Muñoz-Espin D. 2020, 'Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity', Aging Cell, 19, e13142.

- Galiana I ...//... Serrano M, Martinez-Mañez R & Orzaez M. 2020, 'Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic', Journal Of Controlled Release : Official Journal Of The Controlled Release Society, 323, 624 - 634.

- Wilkes MC...//... Serrano M, Flygare J & Sakamoto KM 2020, 'Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase', Nature Communications, 11, 3344.

- Cash TP ...//... Serrano M & Sainz Jr B 2020, 'Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells', Cancers, 12, 1790.

Selected research activities

Creation of the startup company Rejuversen, AG, in Switzerland.  The main goal of this company is to develop immunological strategies that eliminate senescent cells from cancer.