Research Projects

Current Projects

Cell cycle targets & Cancer

Cell proliferation & differentiation

Cell cycle & Metabolism

Pluripotency & Regenerative medicine

Breast cancer and CDK inhibitors

Group History

Since 2005, our work at the Cell Division and Cancer group at the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncológicas CNIO) focuses on the study of the functional relevance of cell cycle regulators and microRNAs involved in cell proliferation and differentiation. These studies have contributed to improving our understanding of the basic machinery of the cell cycle and its implications in therapeutic strategies directed against cell proliferation in cancer.

Our most recent work has focused on the analysis of mitotic regulators such as quinases (Plk, Aurora, Mastl), phosphatases (Cdc14, PP2A-B55), proteins involved in ubiquitin-dependent degradation (APC/C-Cdh1, Cdc20) and some regulators of the spindle checkpoint (securin, Hec1). In the past, our group has reported the characterization of a new member of the Polo-like kinase family (de Carcer et al., Mol Cell Biol 2011), and the relevance of Aurora A and B kinases in development and cancer (Fernandez-Miranda et al., Development 2011; Perez de Castro et al., Cancer Res 2013). Data from our work on mitotic exit (Manchado et al., Cancer Cell 2010) led to the identification of Mastl as a new kinase whose inhibition is required for cell cycle exit. We later reported an essential function of this kinase ion preventing mitotic collapse due to activation of PP2A phosphatases (Alvarez-Fernandez et al., PNAS 2013). Our group also generated the first models of APC/C-Cdh1/Cdc20 deficient mice and their involvement in several cell cycle processes and neural development (Garcia-Higuera et al. Nat Cell Biol 2008, Eguren et al., Nat Commun 2013; Eguren et al. Cell Reports 2014). More recent work identified the relevance of mitophagy and its consequences in energy control during mitotic arrest (Domenech et al., Nat Cell Biol 2015). His group is also interested in related topics such as the control of proliferation by microRNAs (Bueno et al., Blood 2011) or the molecular and cellular regulation of unconventional cell cycles in vivo (Trakala et al., Dev Cell 2015; Trakala et al., Blood 2015). Our recent work has also characterized the relative relevance of Plk1 as an oncogene or tumor suppressor (de Carcer et al, Nat. Commun. 2018) and an unexpected role of this kinase in the contraction of smooth muscle cells and the control of blood pressure (de Cárcer et al., Nat. Med. 2017).

More recently, our lab has become interested also on deciphering the mechanisms that potentiate pluripotency and fine tune the balance between stemness and differentiation.  Part of the team is focused on stem cell biology, trying to understand how progenitor cells and also cancer stem cells control their differentiation capacity and to design novel strategies for boosting those processes (Salazar-Roa et al., EMBO J., 2020).

Finally, we have a long-standing interest in the relevance of cyclin-dependent kinases (CDKs) and their regulators in cancer biology and therapy. In particular, we are interested in improving the application of CDK4/6 inhibitors in cancer therapy (Salvador et al., Cancer Cell 2020; Alvarez-Fernandez & Malumbres, Cancer Cell 2020) and discovering new therapeutic strategies based on inhibitors of this family of proteins.

For a complete list of publications please visit our Publications page.

For the list of mouse models generated in our lab and genotyping conditions please visit our Resources page.

 

Funding

The CNIO Cell Division and Cancer Group has been funded by major Spanish Agencies such as the MINECO, Comunidad de Madrid, Fundación Científica de la Asociación Españona contra el Cáncer (AECC), Fundación Ramón Areces, La Caixa, etc. We are part of several networks on the cell cycle (CAM) or biology of Cell Differentiation and Cancer (Consolider-Excellence Networks-MINECO). In addition, we have received funding from international agencies such as the Association for International Cancer Research (AICR; now Worldwide Cancer Research) or the EU as part of the European Consortium for the study of mitosis (MitoSYS; 7FP) or a consortium interested in the molecular basis of microcephaly (ERA-NET Neuron). M. Malumbres is coordinator of a regional network on the cell cycle in Madrid and a MINECO network of Excellence on Cell proliferation including 9 additional groups in Spain. The laboratory has also been funded by research agreements with pharmaceutical companies (Merck, Pfizer, Prosenestar and Lilly).