Laureano De La Vega

Biography

Laureano de la Vega is a biochemist graduate from the University of Cordoba (Spain), he finished his PhD in Biochemistry in 2007 obtaining the highest degree, Summa Cum Laude, for his work investigating the molecular mechanisms regulating HIV latency. Following this, he moved to Giessen(Germany) to join the team of Prof. Lienhard Schmitz as a postdoctoral researcher from 2007 to 2013. During that time his research was focused on post-translational modifications of HIPK2, an important regulator of cell growth, cell death and differentiation. In 2013 he moved to Dundee where he started his own group focused on regulation of cancer-related proteins by post-translational modification and their relevance in tumour progression and chemoresistance acquisition

Research Interest

Stress Responses To sustain the cellular homeostasis that is vital to the normal functions of cells, certain cellular programs have evolved to respond to stress in a dynamic environment which is essential for adaptation and cell survival. Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Example of stress responses pathways include the p53, NRF2, or NF-κB pathways. These stress responses are by definition acute, and their transient activation help normal cells to cope with a variety of cellular stresses. On the other hand, most cancer cells are under some type of stress (i.e. DNA damage stress, mitotic stress, metabolic stress, proteotoxic stress, or oxidative stress), and in order to survive, cancer cells depend on the activation of stress response pathways. Additionally, it has become apparent that aberrant sustained activation of stress responses can also promote metabolic activities that support cell proliferation, tumour growth and resistance to therapy. Two clear examples of this are the gain-of-function mutations found for the p53 and the NRF2 pathway in a variety of tumours. Modulating the outcome of cellular stress responses toward cell death in tumour cells without affecting surrounding normal cells, is one of the ultimate aims in the development of new cancer therapeutics. In that sense, our lab is focused in obtaining a detailed understanding of cellular stress response pathways and their aberrations in cancer. For that, we are interested not only on key master regulators of stress responses (i.e. NRF2 or p53) but as well in the upstream regulatory pathways that modulate their activity (i.e. upstream kinases). HIPK/DYRK family Homeodomain-interacting protein kinases (HIPKs) are a subfamily of the Dual specificity tYrosine Regulated Kinase (DYRK) family of kinases. These kinases function as hubs for a wide variety of stress signals, ranging from DNA damage and hypoxia to reactive oxygen species and metabolic stress. HIPK/DYRKs function as integrators for these stress signals and modulate different downstream pathways in order to allow cells to cope with these situations. Different posttranslational modifications modulate the activity and physiological role of HIPK/DYRKs, and the study of how their activity is regulated in different phatophysiological scenarios is an important line of investigation in cancer research. Based on the literature and on previous studies from the lab it has become apparent that HIPK/DYRKs can play a dual role in cancer; either inducing apoptosis or promoting cell survival. While the pathways involved in their tumour suppressor role are relatively well studied, the underlying mechanisms mediating their pro-survival function(s) are not well characterised. Specifically, we are interested in i) understanding how this family of kinases is regulated in cancer cells; ii) identifying novel HIPK/DYRK-regulated pro-survival/oncogenic pathways and iii) to identify the basis for such functional duality in cancer, as it will inform us in which type of cancer or under which conditions (i.e initial stages of cancer versus well stablished cancers) these kinases can support cancer cell survival and tumour growth.