Cancer Heterogeneity and Plasticity

Bruno Sainz, Jr.  PhD

Senior Researcher, Head of Cancer Stem Cells and Fibroinflamatory Microenvironment Group, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) - CSIC-UAM;
Head of Biomarkers and Personalized Approach to Cancer (BIOPAC) Group;
Co-director of Area 3, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad Autónoma de Madrid, Spain
Research Interests: Cancer; cancer stem cells (CSC); CSC-mediated tumorigenesis and metastasis; pancreatic cancer; colon cancer; fibroinflammatory tumor microenvironment; tumor-associated macrophages; pre-metastatic tumor niche; immune-based anti-cancer therapies; anti-CSC drug screening; small animal models of cancer and infectious disease (chimeric mice and transgenic mice); nanotechnology; viral-mediated cancer
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Dr. Bruno Sainz earned his PhD in Microbiology and Immunology from Tulane University in New Orleans, LA, USA in 2005. His early scientific career focused on understanding the role the innate immune system in viral infections, and was funded by a National Institutes of Health (NIH, USA) NRSA research award. As a postdoctoral fellow at the Scripps Research Institute (2005-2006), he developed a more physiologically relevant hepatocyte culture system to study Hepatitis C Virus (HCV) infection in vitro. The more differentiated hepatocyte system also permitted me to independently discover that the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol absorption receptor is an HCV entry factor and the clinically-available and FDA-approved NPC1L1 antagonist ezetimibe (Zetia) can potently block HCV uptake in vitro and in mice with human liver grafts. These findings translated into a 2012 Nature Medicine publication, a US patent application, invited talks and presentations at international conferences and institutes and several follow-up publications. As a semi-independent investigator at the CNIO in Spain from 2011-2014, he changed his research focus and began to study cancer stem cell (CSC) biology in pancreatic cancer. He identified several immune proteins that have powerful pro-CSC properties, including the human cationic antimicrobial protein 18 (hCAP-18)/LL-37 peptide and the interferon-stimulated gene 15 protein. The sum of these studies has advanced our understanding of CSC pathobiology. In addition to the contributions described above, his contributions to science and specifically to the CSC field are best exemplified by his publications aimed at dissecting the biological and molecular signatures of CSCs. From 2014-2020, as an independent Ramón y Cajal investigator (with a positive I3 evaluation) at the UAM, his laboratory discovered a new inherent biomarker present in CSCs, known autofluorescence, which is the result of riboflavin accumulation in ABCG2-coated intracellular vesicles exclusively found in CSCs. Using this marker, we have learned that CSCs are distinct from non-CSCs at the epigenetic level (e.g., genome methylation and miRNA profiles) and these differences in methylation and miRNA expression are necessary for the maintenance of these cells. In addition, he has also learned that CSCs are metabolically different than non-CSCs. While non-CSCs meet their energy requirements via glycolysis, CSCs depend on mitochondrial respiration (i.e., oxidative phosphorylation) to survive. Since July 2020, He is a Cientifico Titular in the Department of Cancer Biology as the Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM). He also leads the “Biomarkers and Personalized Approach to Cancer (BIOPAC)” Group in Area 3: Cancer at the IRYCIS, where he is also Co-Director of the Area, and I am Co-PI of Dr. Alfredo Carrato’s CIBERONC group. His accomplishments and research have resulted in 95 publications, 3 Triennios, 2 Quinquenniums and 4 Sexseniums, 4 defended PhD thesis, several awarded US (Cancer Research Institute, Concern Foundation), Spanish (Ramón y Cajal Merit Award, ISCIII, AECC, ACANPAN, Beca FERO) and European (EURO-NanoMed, ERC-PoC) grants, 3 patents, numerous invited talks and presentations, editorial affiliations and international recognition. I have a broad background in immunology, microbiology and oncology, with specific expertise in pancreatic cancer, small animal models of cancer and drug discovery.

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