Centre for Discovery Brain Sciences
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Dr Blanca Díaz Castro

Our aim is to deepen the understanding of the molecular and cellular mechanisms that link brain vascular dysfunction and dementia with the hope that our results will be translated into the development of early diagnostic methods and treatments.

Dr Blanca Díaz Castro

UK Dementia Research Institute Fellow

  • Chancellor's Building
  • 49 Little France Crescent Edinburgh
  • EH16 4SB

Contact details

Personal profile

  • 2019 - Present: Group Leader (Fellow), University of Edinburgh, UK Dementia Research Institute.

  • 2017 - 2019:       Assistant Project Scientist IV at University of California, Los Angeles (Advisor: Prof. Baljit Khakh).

  • 2014 - 2017:       Postdoc at University of California, Los Angeles (Advisor: Prof. Baljit Khakh).

  • 2013 - 2014:       Postdoc at Northwestern University, Chicago (Advisor: Prof. Peter Penzes).

  • 2006 - 2012:       Ph.D. in Biology, University of Seville, Spain (Advisors: Prof. Dr. Jose Lopez Barneo, Dr. Jose I. Piruat Palomo).

  • 2007 - 2008:       M.S. in Biomedicine, University of Seville, Spain.

  • 2001 - 2006:       B.S. in Biology, University of Seville, Spain.

Research Theme

Research

Unlike other organs, the exchange of substances between the blood and the brain is tightly regulated by a multicellular functional entity called the Blood Brain Barrier (BBB). The BBB provides a cellular boundary that restricts the invasion of toxins and pathogens into the brain, controls the uptake of molecules from the blood, metabolizes nutrients and clears the brain of toxic by-products. Failure in BBB homeostasis leads to severe neurological disorders.

Remarkably, BBB dysfunction is one of the earliest observations in neurodegenerative diseases and precedes neurodegeneration. In spite of the crucial function of the BBB and efforts made to understand the mechanisms that underlie its dysfunction, there are important aspects of BBB physiology that remain largely unexplored. How is the BBB maintained? How do the BBB cellular components interact? What are the molecular pathways leading to BBB dysfunction?

The two most widespread components of the BBB are the brain endothelial cells (BECs) and the astrocytes. BECs form the first barrier between the blood and the brain parenchyma thanks to protein complexes called tight junctions (TJs) that keep BECs closely bound. Astrocytes have a unique strategic position in the brain by intimately contacting neurons and covering the vasculature of the brain through specialized structures called astrocyte end-feet.

The three main objectives of our research are:

1. Comparative molecular characterisation and functional exploration of astrocyte and BEC interactions during BBB maturation, and in neurological disease. 

2. Functional mechanistic assessment, in vivo and in vitro, of new astrocyte-BEC interaction pathways unveiled by health and disease comparative studies.

3. Development of research tools that will allow a better understanding of the BBB in health and disease.

The understanding of the BBB cell interactions is necessary to better comprehend the BBB maintenance and pathology. This knowledge will allow us to identify therapeutic targets and design new treatments.

Funding

Team members

  • Isabel Bravo-Ferrer
  • Steve Hill

Collaborations

Selected publications

Diaz-Castro B.#, Bernstein A.M., Coppola G., Sofroniew M.V., and Khakh B.S.#. Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation.  Cell Reports 2021, Aug 10;36(6):109508. PMID: 34380036 (# Corresponding authors) 

Nagai J., Bellafard A., Zhe Q., Yu X., Ollivier M., Gangwani M.R., Diaz-Castro B., Coppola G., Schumacher Bass S M., Golshani P., Gradinaru V., Khakh B.S. Astrocyte Gq GPCR signaling attenuation in vivo. Neuron 2021 Jun 10;S0896-6273(21)00376-7.

Escartin C.*#, Galea E.*#, Lakatos A.§, O’Callaghan J.P.§, Petzold G.C.§, Serrano-Pozo A.§, Steinhauser C.§, Volterra A.§, Carmignoto G.§, Agarwal A., Allen N.J.,  Araque A., Barbeito L., Barzilai A., Bergles D.E, Bonvento G., Butt A.M, Chen W.T., Cohen-Salmon M., Cunningham C., Deneen B., De Strooper B., Díaz-Castro B., Farina C., Freeman M., Gallo V., Goldman J.E., Goldman S.A, Götz M., Gutiérrez A., Haydon P.G., Heiland D.H., Hol E.M., Holt M.G., Iino M., Kastanenka K.V., Kettenmann H., Khakh B.S., Koizumi S., Lee C.J., Liddelow S.A., MacVicar B.A., Magistretti P., Messing A., Mishra A., Molofsky A.V., Murai K., Norris C.M, Okada S., Oliet S.H.R., Oliveira J.F., Panatier A.,Parpura V., Pekna M., Pekny M., Pellerin L., Perea G., Pérez-Nievas B.G., Pfrieger F.W., Poskanzer K.E., Quintana F.J., Ransohoff R.M., Riquelme-Perez M., Robel S., Rose C.R., Rothstein J., Rouach N., Rowitch D.H., Semyanov A., Sirko S., Sontheimer H., Swanson R.A., Vitorica J., Wanner I.B., Wood L.B., Wu J., Zheng B., Zimmer E.R., Zorec R., Sofroniew M.V.*#, Verkhratsky A.#. Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience (in press). DOI: 10.1038/s41593-020-00783-4.

Murphy-Royal C., Johnston A., Boyce A., Diaz-Castro B., Institoris A., Peringod G., Zhang O., Stout R., Spray D., Thompson R., Khakh B., Bains J., and Gordon G. Stress gates an astrocytic energy reservoir to impair synaptic plasticity. Nature Communications 2020, Apr 24;11(1):2014.

Diaz-Castro B., Gangwani M., Yu X., Coppola G. and Khakh B.S. Astrocyte molecular signatures in Huntington’s disease. Science Translational Medicine 2019 Oct 16;11(514).

Moye S.L., Diaz-Castro B., Gangwani M.R. and Khakh B.S. Visualizing Astrocyte Morphology Using Lucifer Yellow Iontophoresis. Journal of Visual Experiments 2019 Sep 14;(151).

Chai H.*, Diaz-Castro B.*, Shigetomi E., Monte E., Octeau J.C., Yu X., Cohn W., Rajendran P.S., Vondriska T.M., Whitelegge J.P., Coppola G. & Khakh B.S. Neural circuit-specialized astrocytes: genomic, proteomic, morphological and functional evidence. Neuron 2017 95(3):531-549.e539. *Equally contributing authors.

Blizinsky K.D., Diaz-Castro B., Forrest M.P., Schürmann B., Bach A.P., Martin-de-Saavedra M.D., Wang L., Csernansky J.G., Duan J., Penzes P. Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub. Proc Natl Acad Sci 2016 113(30):8520-5.

Jiang R., Diaz-Castro B., Looger L. L. & Khakh B. S. Dysfunctional calcium and glutamate signaling in striatal astrocytes from Huntington’s disease model mice. J Neurosci 2016 36(12):3453-70.

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here