Luis del Peso Ovalle

Biosketch

Oncogenes, programmed cell death and gene expression. The discovery of activated RAS genes in human cancer in 1982 concept of the cellular oncogene and triggered an intense effort to understand their biochemistry and biology. For this reasons, for my PhD (1991-1996) I decided to join this hot topic of research to study the role of ras family proteins on signalling pathways leading to cell proliferation under the supervision of Dr. Juan Carlos Lacal (CSIC). My thesis work contributed to support phospholipase D as target of RAS and revealed a role for RHO members, a sub-family of RAS, in the promotion of metastasis (https://www.ncbi.nlm.nih.gov/pubmed/9444953). After completing my PhD, I joined Dr. Nuñez's lab at University of Michigan (MI, USA) for posdoctoral training (1996-1999). Dr. Nuñez's group was working on the identification of the molecules involved in the process of apoptosis, an exciting new topic at that time. Exploiting my background on signal transduction, I proposed a project to gain insight on the mechanisms by which growth factors supress cell death. This work uncovered the first link between extracellular signals and the apoptosis machinery and resulted in a seminal publication describing the PI3K/Akt/BAD axis (https://www.ncbi.nlm.nih.gov/pubmed/9381178). Next, aiming to identify new molecules regulated by the PI3K/Akt pathway, we found a transcription factor, FKHR, whose activity was regulated in response to extracellular signals through this pathway (https://www.ncbi.nlm.nih.gov/pubmed/10602488). This study sparked my interest in the regulation of gene expression and accepted a job position at the Hospital de La Princesa where Dr. Landazuri’s group was starting a research line on the Hypoxia Inducible Factor (HIF), a transcription factor responsible for the cellular adaptation to chronic hypoxia. Thus, in 2000, I started my our research group on the biology of hypoxia. Firstly, capitalizing on my background, we investigated the effect of hypoxia on the induction of apoptosis (https://www.ncbi.nlm.nih.gov/pubmed/11294857)and the (lack of) role of the PI3K/Akt on the regulation of HIF by oxygen Next, we focused on the identification of novel HIF-target genes by the computational prediction of HIF-binding sites. Our first work on this direction led us to the identification the long-sought hypoxia-response element on EGLN3, a gene encoding for an oxygen-sensor (https://www.ncbi.nlm.nih.gov/pubmed/15823097). It is worth mentioning that we approach most of our research projects by a combination of computational and experimental techniques, an strategy that has allowed us to tackle old problems, such as identification of HIF-target genes, from novel angles (https://www.ncbi.nlm.nih.gov/pubmed/20061373). To to gain further training on computational biology, I spend a year (2011-2012) as a vissiting professor at the University of British Columbia working in the laboratory of Dr. Wyeth Wasserman, a world leading expert on bioinformatics approaches to study transcription factors. Since then, we use a blend of web lab and in silico approaches to continue exploring the regulation of transcription by hypoxia and its role on human disease. In this regard, we are currently interested in understanding how genetic variation in HIF binding regions affect the transcriptional response to hypoxia and its role in disease progression (https://www.ncbi.nlm.nih.gov/pubmed/27625398).

Finally, my position as associate professor includes research and teaching responsibilities. I find both activities complementary and equally rewarding. Accordingly, I have also participated in projects trying to improve our teaching methodologies (https://www.ncbi.nlm.nih.gov/pubmed/23483652). I currently teach undergraduate courses on “Bioinformatics and Systems Biology” and “Programming Tools for Biochemistry and Molecular Biology” and graduate courses on “Applied Statistics” and “Regulation of Gene Expression”

Gestión

• Nov_2015- Miembro Claustro UAM en representación de Profesores Doctores con Vinculación Permanente.
• Ene_2016- Miembro Junta Facultad (Medicina) en representación Profesores Permanentes.
• Oct_2012- Miembro Comisión Grado Bioquímica.
• Jul_2013- Coordinador 4º curso del Grado en Bioquímica.
• Dic_2007-Dic_2010 Secretario Departamento Bioquímica.

PhD theses supervised

• Salvador Naranjo (Feb 2006) “Regulation of Hypoxia Inducible Transcription Factor 2 by NGF and effect of hypoxia on PC12 cells viability”. Cum Laude.
• Yolanda Cuevas (May 2006) “Development of a conditional replicative adenovirus (Ad-9XHRE1A) targeting tumors with active HIF pathway. Antitumoral efficacy against VHL-defficient clear cell renal carcinomas” Cum Laude.
• Nuria Pescador (Mayo 2007) “Identification of cis-elements responsible for gene expression regulation in response to hypoxia Inducible Factors.” Cum Laude.
• María Luisa Alcaide (Jun 2009) “Generation of a yeast system to study the regulation of the mammalian Hypoxia Inducible Factor. Optimization to identify small molecules affecting HIF prolyl hydroxylases activity” Cum Laude.
• Diego Villar (Feb 2010) “The role of binding selectivity in the HIF pathway: biochemical identification of a substrate binding region in HIF prolyl hydroxylases and in silico prediction of ancillary sequences contributing to HIF DNA binding selectivity” Cum Laude, European Thesis.
• Amaya Ortiz (Sep 2010) “A computational approach for the identification of novel Hypoxia Inducible Factor target genes”. Cum Laude.
• Laura Gomez (Dic 2013) ”Regulation of EFNA3 expression by hypoxia through a novel lncRNA-mediated mechanism. A potential role in cancer metastasis” Cum Laude, European Thesis.
• Laura Deguiz (Dic 2015) “Identification of non-coding genetic variants in samples from hypoxemic respiratory disease patients that affect the transcriptional response to hypoxia.” Cum Laude.
• María Tiana (Ene 2016)” Characterization of the molecular machinery responsible for gene downregulation during hypoxia by a combination of computational and experimental tools” Cum Laude, European Thesis.