Cell cycle targets & Cancer
Cell proliferation & differentiation: genetics & epigenetics
Cell cycle & Metabolism
Pluripotency & Regenerative medicine
The Cell Division and Cancer group (CNIO) is focused to the in vivo analysis of cell cycle regulators and their therapeutic potencial. These studies have addressed the in vivo characterization of the mammalian cell cycle and their deregulation in human cancer. After obtaining the Ph.D. degree In Spain, Dr. Malumbres moved for a postdoctoral stay at the New York University Medical Center for a training in the field of oncogenes and tumor suppressors. In this institution, his work was focused to the molecular biology of Ras oncogenes in carcinogen-induced tumors and the interaction between Ras and the cell cycle regulators.
Since 2005, our work at the Cell Division and Cancer group at the Spanish National Cancer Center (CNIO) focuses on the study of the functional relevance of cell cycle regulators and microRNAs using in vivo models, and specifically genetically-modifed mice. 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 group also reported the role of specific microRNAs in cell proliferation including the first report of a microRNA controlling a tumor-associated translocation protein and it has relevant implications in cancer therapy.
Current work is 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).
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.
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.
The CNIO Cell Division and Cancer Group has been funded by major Spanish Agencies such as the MICINN, 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 Cancer (Consolider-MICINN). 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 is also funded by research agreements with pharmaceutical companies (Pfizer and Prosenestar).
Dr. Malumbres has supervised 17 PhD students in the past + 5 students currently in the lab, as well as a number of master students, etc. Some of the previous members of the group are now group leaders in Germany, Switzerland or Spain.