Professor Rafael Carazo Salas

WELCOME TO THE CARAZO SALAS’ INTEGRATIVE STEM CELL BIOLOGY LABORATORY

The Carazo Salas Lab is interested in understanding the cell biological mechanisms that control the efficiency and specificity of human stem cell differentiation, and how those mechanisms can be leveraged to improve the production of therapeutically-useful cells & tissues for Personalised, Regenerative Medicine.

Qualification and history

  • 2001:           PhD European Molecular Biology Laboratory, Heidelberg, Germany
  • 2002-2007:  Postdoc, Cancer Research UK, LRI, London, UK
  • 2007:           Research Associate, The Rockefeller University, New York, USA
  • 2008-2010:  Group Leader, ETH Zurich, Switzerland
  • 2010-2016:  Group leader, Gurdon Institute, Genetics Department, Cambridge Systems Biology Centre & Pharmacology Department, University of Cambridge, UK
  • 2016 - :        Professor and Chair in Biomedical Sciences, University of Bristol, UK          

Awards:

  • 2002-2005:   EMBO and HFSP Postdoctoral Fellow
  • 2009-2012:   HFSP Young Investigator
  • 2010-2016:   ERC Starting Independent Researcher

Vision

The Regenerative Medicine of the future will rely on being able to produce a wide variety of “designer” tissues of choice (neurons, heart cells, liver cells, etc) that can be used for tissue replacement in the clinic. This dream has become achievable thanks to the Nobel Prize winning discovery a decade ago of human induced Pluripotent Stem (iPS) cells, a revolutionary technology allowing any cells in our body to be converted into pluripotent stem cells from which almost any desired target tissue of choice could be derived by differentiation in vitro.

However, key challenges have to be overcome before the promise of stem cell therapeutics becomes a reality. First, we do not yet know how to control with precision the differentiation of iPS cells into the target tissues of choice. Most procedures to induce differentiation of iPS cells remain quite inefficient, unspecific, and unsafe (i.e. some of the cells obtained after differentiation retain the capacity to keep proliferating and make tumours, for reasons that are not understood). Secondly, even when generated in exactly the same way in the laboratory, it is now clear that iPS cells derived from some people can be programmed better into target tissues than those from other people, for reasons that remain unknown.

Our work aims to apply quantitative, data driven approaches to discover the molecular mechanisms that control the specific, efficient and safe differentiation of human (iPS) stem cells into specific target cells/tissues, and exploit that information to optimize cell/tissue production in a precise, personalized manner. In the long term this will help elucidate how to produce therapeutically-useful cells & tissues of choice for Personalised, Regenerative Medicine research and applications.

Mission and impact

We aim to understand how to produce specifically, efficiently and robustly “designer” cells/tissues of choice using a person’s own stem cells, for Regenerative Medicine and therapeutics applications.

Approach

In the past decade, the Carazo Salas group has pioneered the development of quantitative (high-throughput/high-content) microscopy cellular phenotyping strategies and biological Big Data approaches to study cells as integrated systems and wire the molecular networks that control them. This has allowed us to systematically discover hundreds of genes controlling & linking fundamental cell biological processes like cell polarity, the cell cycle, cell shape and microtubule organization, and to provide a comprehensive picture of how those processes interact in a cause-effect manner.

Building on that work, our group has recently established innovative experimental and computational technologies to investigate human stem cell differentiation quantitatively and spatiotemporally at single cell resolution, using human pluripotent stem cells (Embryonic Stem (ES) and iPS cells) in vitro. These include: (1) experimental protocols for in vitro culturing, differentiation and imaging by high-throughput timelapse microscopy human pluripotent stem cells, (2) fluorescent reporter combinations that allow to simultaneously monitor & extract through days the proliferation and differentiation characteristics of “live” pluripotent stem cells at single cell level, and (3) image analysis & statistical analysis pipelines to analyse the microscopy data obtained from 1000s of stem cells across multiple stem cell lines, to compare quantitatively how cell lines from different individuals differ in their capacity to become differentiated along lineages of choice and to assess the role of stem cells’ pheno-genotypic heterogeneity in controlling cell differentiation.

Using this approach our group is currently investigating systematically which proliferative characteristics (cell growth, division, migration and death rates, position of a cell within a cell colony, size of the cell colony, etc) of human pluripotent stem cells are good predictors of their capacity to become differentiated, as a way to identify properties that might be manipulated to predictively improve personalised, targeted cell differentiation in vitro.

Selected publications

Please find further publications on Explore Bristol Research.

  1. Reconstructing regulatory pathways by systematically mapping protein localization interdependency networks. Dodgson J, Chessel A, Vaggi F, Giordan M, Yamamoto M, Arai K, Madrid M, Geymonat M, Abenza JF, Cansado J, Sato M, Csikasz-Nagy A, Carazo Salas RE. BioRxiv 2017 Mar. doi:10.1101/116749.
  2. The Image Data Resource: A Scalable Platform for Biological Image Data Access, Integration, and Dissemination. Williams E, Moore J, Li S, Rustici G, Tarkowska A, Chessel A, Leo S, Antal B, Ferguson RK, Sarkans U, Brazma A, Carazo Salas RE, Swedlow JR. Nature Methods 2017, 14, 775–781. Resource available at https://idr.openmicroscopy.org/
  3. Big Data-Driven Stem Cell Science and Tissue Engineering: Vision and Unique Opportunities. Del Sol A, Thiesen HJ, Imitola J, Carazo Salas RE. Cell Stem Cell 2017. Feb 2, 20:157-160.
  4. Mineotaur: a tool for high-content microscopy screen sharing and visual analytics. Antal B, Chessel A, Carazo Salas RE. Genome Biology 2015. Dec 17;16(1):283.
  5. A genomic multi-process survey of machineries that control and link cell shape, microtubule organisation and cell cycle progression. Graml V, Studera X, Lawson JL, Chessel A, Geymonat M, Bortfeld-Miller M, Walter T, Wagstaff L, Piddini E, Carazo Salas RE. Developmental Cell 2014, Oct 27;31: 10.1016/j.devcel.2014.09.005. Journal Cover.

Funding

Our lab has been generously funded by many funders through the years. Previous funders include the European Research Council (ERC), Human Frontier Science Program (HFSP), the Wellcome Trust and the BBSRC. Current funding comes partly from the Wellcome Trust and the EPSRC.

Professor Rafael Carazo Salas
Edit this page