Paco Real
Epithelial Carcinogenesis Group Leader
Spanish National Cancer Research Centre-CNIO; U. Pompeu Fabra
Friday 27th November 2020 11.00 CET
Experimental designs to harness the potential of genetic mouse models in combination with human data to reveal gene function
Abstract:
“All models are wrong but some are useful” (G. Box). In translational research, the best model is the patient. However, it is not possible to perform all kinds of research in human subjects. Therefore, we use models to learn about questions we cannot address in humans. I will provide examples of how translation occurs in multiple directions. Sometimes, we make initial observations in samples from humans, then move to cells or genetically engineered mice to address mechanisms and perform organism-level studies. On other occasions, initial observations are made in model systems and we search their implications in disease by studying them in patients. These iterative processes allow progress in knowledge acquisition, ensuring that biological questions are properly addressed and their meaning to human health is best harnessed. I will illustrate this with some recent experimental data from our laboratory.
Key references:
Flández M, et al. Nr5a2 heterozygosity sensitizes to, and cooperates with, inflammation in KRasG12V-driven pancreatic tumorigenesis. Gut 2014; 63:647.
Cobo I, et al. Transcriptional regulation by NR5A2 links cell differentiation and inflammation in the pancreas. Nature 2018; 554:533.
Biography:
I trained as a medical oncologist at Memorial Hospital, New York, where I also carried out research on tumor immunology (1981-1986). After 2 years as a staff physician, I returned to IMIM, Barcelona, where I set up from scratch a new research program in cancer cell and molecular biology (1988). In 2003, I became Professor of Cell Biology at UPF where I continue to teach in the undergraduate and graduate programs. In late 2007 I joined the CNIO. Our laboratory has focused on the study of the cell and molecular biology of pancreatic and bladder cancer. Because the challenges posed by these two tumor types are very different, our approaches to them are also different. In pancreatic cancer, we focus on the identification of early mechanisms that favor tumor development. These studies are not possible in humans; therefore, we use genetic mouse models hoping that they will guide us to develop better strategies for identification of subjects at risk of pancreatic cancer. As of bladder cancer, we have as a major aim to understand better the genetic pathways leading to the various bladder cancer subtypes. For this, we combine the use of state-of-the art genetic tools (whole exome and whole genome sequencing) with the establishment of large patient cohorts that allow us to test the translational potential of our findings. We combine the use of genetic mouse models and organoids to study the function of relevant genes. We have a major interest in developing (and replicating) tools for improved treatment of patients with muscle-invasive tumors.