Cell Biologist with research and teaching interests in the fields of neuroimmunology and vascular cell biology.
Professor of Biology, since 1999.
Our current research is on the development of nanoparticles as carriers for therapeutic cytokines and transgenes into the CNS. We have shown that gold nanocarriers efficiently cross brain endothelium in vitro and enter the CNS in vivo. We also work on targeting systems for nanocarriers, using peptides directed against receptors on the endothelial cells. We are now optimising the attachment of therapeutic cargo molecules to the nanocarriers, and improving targeting to glial cells in the CNS. The most recent work involves the development of a blood-brain barrier model using endothelium differentiated from human stem cells. This work has been supported by our Industrial partners Midatech Pharma plc and Medimmune, Sheffield Hospital Trust and the European Union, Innovative medicines initiative.
Previous research has been primarily concerned with the mechanisms by which immune reactions and inflammation develop in the CNS, and the way in which leukocyte migration into the brain is controlled. To understand inflammation in the brain we have undertaken a great deal of work on the blood brain barrier and brain vascular endothelial cells. We have developed several in vitro tissue culture systems to investigate the mechanisms by which brain endothelium differentiates and the role of transcription factors. Earlier studies investigated how inflammatory cytokines and micro-RNAs affect the barrier properties of brain endothelium.
I have a particular interest in the use of multimedia for developing virtual laboratories, and have lead work on the development of virtual microscopes for the OpenScience laboratory. These include a JISC-funded slide collection 'Histology and Histopathology (320 sections) and a collection for teaching A-level biology (100 sections), which was funded by the Wolfson Trust. This resource has now been developed and incorporated into a MOOC Histology and histopathology: Disease under the microscope.
I am author and editor of a number of text books and CD-ROMs on basic and clinical Immunology.
I currently teach Infectious Disease, (SK320), and contribute as section on gene transcription and translation to the level-3 bioscience course (S317). When our teaching labs reopen, I will be tutoring on the level-3 practical course SS032, again. I have also contributed sections on immunological techniques in two new courses S285 (genetic variation in cytochromes) and S290 (autoimmunity and autoimmune disease). These courses both include extensive sets of virtual laboratory experiments based on the ELISA and qPCR techniques. I maintain external teaching commitments in neuroimmunology on MSc courses at the Institute of Psychiatry, (KCH) and the London School of Hygiene and Tropical Medicine.
We have worked closely with Midatech Pharma plc on the development of gold nanocarriers for the CNS and with Medimmune on targeting systems for brain endothelium. This work has also been supported by Sheffield Hospital Trust, and we have external collaborators at the University of Bristol.
We are collaborating with Prof Mehmet Kaya, Koc University, Istanbul, on nanocarrier delivery to the brain. We have recently hosted visiting researchers and a PhD student from the Universities of Madrid and Barcelona, as well as four visiting B.Tech students from ENSTBB (Bordeaux).
|Biomedical Research Network (BRN)||Network||Faculty of Science|
|Role||Start date||End date||Funding source|
|Lead||01 Jan 2019||31 Dec 2023||EC (European Commission): FP (inc. Horizon Europe, H2020, ERC)|
DISCOVERY AND CHARACTERISATION OF BLOOD-BRAIN BARRIER TARGETS AND TRANSPORT MECHANISMS FOR BRAIN DELIVERY OF THERAPEUTICS TO TREAT NEURODEGENERATIVE & METABOLIC DISEASES
|Role||Start date||End date||Funding source|
|Co-investigator||01 Sep 2015||31 Aug 2019||EC (European Commission): FP (inc. Horizon Europe, H2020, ERC)|
The general aim of the current proposal is to the function of the neurovascular unit across species and the impact of several conditions (development, inflammation, ageing, exposure to drugs)on the function of the blood-brain barriers. The aims are: 1. Prediciting brain barrier function using in vitro BBB models 2. Brain barriers signature in vertrebrates 3. Brain barriers as therapeutic and diagnostic target The OU will lead the project within the BtRAIN network focused on age-associated changes in gene and microRNA expression at the blood-brain barrier. See the network webpage http://www.btrain-2020.eu/
Endothelial-Derived Extracellular Vesicles Induce Cerebrovascular Dysfunction in Inflammation (2021-09)
Roig-Carles, David; Willms, Eduard; Fontijn, Ruud D.; Martinez-Pacheco, Sarai; Mäger, Imre; de Vries, Helga E.; Hirst, Mark; Sharrack, Basil; Male, David K.; Hawkes, Cheryl A. and Romero, Ignacio A.
Pharmaceutics, 13, Article 1525(9)
Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus (2021-05)
Frias Anaya, Eduardo; Gromnicova, Radka; Kraev, Igor; Rogachevsky, Vadim; Male, David; Crea, Francesco; Hawkes, Cheryl and Romero, Ignacio A.
Neurobiology of Aging, 101 (pp. 273-284)
Tissue distribution and cellular localization of gold nanocarriers with bound oligonucleotides (2021-04)
Fatima, Nayab; Akcan, Ugur; Kaya, Mehmet; Gromnicova, Radka; Loughlin, Jane; Sharrack, Basil and Male, David
Nanomedicine, 16(9) (pp. 709-720)
Comparison of polypeptides that bind the transferrin receptor for targeting gold nanocarriers (2021)
Mcquaid, Conor; Halsey, Andrea; Dubois, Maeva; Romero, Ignacio A and Male, David
PLoS ONE, 16, Article e0252341(6)
EZH2 inhibition: a promising strategy to prevent cancer immune editing (2020-08)
Kang, Ning; Eccleston, Mark; Clermont, Pier-Luc; Latarani, Maryam; Male, David Kingsley; Wang, Yuzhuo and Crea, Francesco
Gold nanocarriers for transport of oligonucleotides across brain endothelial cells (2020)
Fatima, Nayab; Gromnicova, Radka; Loughlin, Jane; Sharrack, Basil and Male, David
PLOS ONE, 15, Article e0236611(9)
Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo (2019-05-06)
Aparicio-Blanco, Juan; Romero, Ignacio A.; Male, David K.; Slowing, Karia; Garcia-Garcia, Luis and Torres-Suarez, Ana
Molecular Pharmaceutics, 16(5) (pp. 1999-2010)
PPARγ agonist-loaded PLGA -PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies (2018-09-20)
Silva-Abreu, Marcelle; Calpena, Ana Cristina; Benito, Pol Andres; Romero, Ignacio A.; Roig-Carles, David; Gromnicova, Radka; Espina, Marta; Ferrer, Isidre; Garcia, Maria Luisa and Male, David
International Journal of Nanomedicine, 13 (pp. 5577-5590)
MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium (2017-04-30)
Cerutti, Camilla; Edwards, Laura J.; de Vries, Helga E.; Sharrack, Basil; Male, David K. and Romero, Ignacio A.
Scientific Reports, 7 (p 45284)
Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues (2016-08-25)
Gromnicova, Radka; Kaya, Mehmet; Romero, Ignacio A.; Williams, Phil; Satchell, Simon; Sharrack, Basil and Male, David
PLoS ONE, 11, Article e0161610(8)
Localisation and mobility of glucose-coated gold nanoparticles within the brain (2016-03-31)
Gromnicova, Radka; Yilmaz, Canan Ugur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather; Williams, Phil; Romero, Ignacio A.; Sharrack, Basil and Male, David
Nanomedicine, 11(6) (pp. 617-625)
A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions (2016-01-21)
Reddy, P; Gromnicova, Radka; Davies, Heather; Phillips, James; Romero, Ignacio A and Male, David
F1000Research, 4, Article 1279
Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation. (2015-03-01)
Wu, Dongsheng; Cerutti, Camilla; Lopez-Ramirez, Alejandro; Pryce, Gareth; King-Robson, Josh; Simpson, Julie E.; van der Pol, Susanne M. A.; Hirst, Mark C.; de Vries, Helga E.; Sharrack, Basil; Baker, David; Male, David K.; Michael, Gregory J. and Romero, Ignacio A
Journal of Cerebral Blood Flow & Metabolism, 35(3) (pp. 412-23)
MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. (2014-06-01)
Lopez-Ramirez, Miguel Alejandro; Wu, Dongsheng; Pryce, Gareth; Simpson, Julie E.; Reijerkerk, Arie; King-Robson, Josh; Kay, Oliver; de Vries, Helga E.; Hirst, Mark C.; Sharrack, Basil; Baker, David; Male, David Kingsley; Michael, Gregory J. and Romero, Ignacio Andres
FASEB Journal, 28(6) (pp. 2551-2565)
Glucose-coated gold nanoparticles transfer across
human brain endothelium and enter astrocytes in vitro (2013-12-05)
Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Pedagannganagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B. and Male, David K.
PLoS ONE, 8, Article e81043(12)
Cytokine-induced changes in the gene expression profile of a human cerebral microvascular endothelial cell-line, hCMEC/D3. (2013-09-19)
Lopez-Ramirez, Miguel Alejandro; Male, David Kingsley; Wang, Chunfang; Sharrack, Basil; Wu, Dongsheng and Romero, Ignacio Andres
Fluids and Barriers of the CNS, 10, Article 27(1)
Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues (2012-10)
Gromnicova, Radka; Romero, Ignacio A and Male, David
PLoS ONE, 7, Article e48189(10)
Role of caspases in cytokine-induced barrier breakdown in human brain endothelial cells (2012)
Lopez-Ramirez, Alejandro; Fischer, Roman; Torres-Badillo, Claudia C.; Davies, Heather A.; Logan, Karen; Pfizenmaier, Klaus; Male, David K.; Sharrack, Basil and Romero, Ignacio A.
Journal of Immunology, 189(6) (pp. 3130-3139)
Amyloid-β-induced occludin down-regulation and increased permeability in human brain endothelial cells is mediated by MAPK activation (2010-01)
Tai, L. M.; Holloway, K. A.; Male, D. K.; Loughlin, A. J. and Romero, I. A
Journal of Cellular and Molecular Medicine, 14(5) (pp. 1101-1112)
Polarized P-glycoprotein expression by the immortalised human brain endothelial cell line, hCMEC/D3, restricts apical-to-basolateral permeability to rhodamine 123 (2009-09-23)
Tai, Leon M.; Reddy, P. Sreekanth; Lopez-Ramirez, M. Alejandro; Davies, Heather A.; Male, A. David K.; Loughlin, A. Jane and Romero, Ignacio A.
Brain Research, 1292 (pp. 14-24)
P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-β (2009-06)
Tai, Leon M.; Loughlin, A. Jane; Male, David K. and Romero, Ignacio A.
Journal of Cerebral Blood Flow and Metabolism, 29(6) (pp. 1079-1083)
Transcriptional control of occludin expression in vascular endothelia: regulation by Sp3 and YY1 (2009-03)
Sade, Hadassah; Holloway, Karen; Romero, Ignacio A. and Male, David
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1789(3) (pp. 175-184)
Expression of chemokines and their receptors by human brain endothelium: Implications for multiple sclerosis (2009-03)
Subileau, Eve A; Rezaie, Payam; Davies, Heather; Colyer, Frances; Greenwood, John; Male, David and Romero, Ignacio A
Journal of Neuropathology and Experimental Neurology, 68(3) (pp. 227-240)
Expression and induction of p-glycoprotein-1 on cultured human brain endothelium (2009)
Male, David K.
Journal of Cerebral Blood Flow and Metabolism, 29(11) (pp. 1760-1763)
Chemokine production and chemokine receptor expression by human glioma cells: Role of CXCL10 in tumour cell proliferation (2008-08)
Maru, Seema V.; Holloway, Karen A.; Flynn, Geraldine; Lancashire, Christine L.; Loughlin, A. Jane; Male, David K. and Romero, Ignacio A.
Journal of Neuroimmunology, 199(1-2) (pp. 35-45)
Action of transcription factors in the control of transferrin receptor expression in human brain endothelium (2007-02-02)
Holloway, Karen; Sade, Hadassah; Romero, Ignacio A. and Male, David
Journal of Molecular Biology, 365(5) (pp. 1271-1284)
Chemokine transport across human vascular endothelial cells (2007-01)
Mordelet, Elodie; Davies, Heather A.; Hillyer, Philippa; Romero, Ignacio A. and Male, David
Endothelium - Journal of Endothelial Cell Research, 14(1) (pp. 7-15)
Blood-brain barrier-specific properties of a human adult brain endothelial cell line (2005-09)
Weksler, B.B.; Subileau, E.A.; Perriere, N.; Charneau, P.; Holloway, K.; Leveque, M.; Tricoire-Leignel, H.; Nicotra, A.; Bourdolos, S.; Tourowski, P.; Male, D.K.; Roux, F.; Greenwood, J.; Romero, I.A. and Couraud, P.O.
FASEB Journal, 19(13) (pp. 1872-1874)
Expression of chemokines on the surface of different human endothelia (2005-08)
Hillyer, Phillipa and Male, David
Immunology and Cell Biology, 83(4) (pp. 375-382)
Microglia in the cerebral wall of the human telencephalon at second trimester (2005-07)
Rezaie, Payam; Dean, Andrew; Male, David and Ulfig, Norbert
Cerebral Cortex, 15(7) (pp. 938-949)
Transient expression of MIDC-8 in the normal mouse brain (2005-04-04)
Rezaie, Payam; Corbisiero, Vanessa and Male, David
Neuroscience Letters, 377(3) (pp. 189-194)
Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration (2003-12)
Hillyer, P.; Mordelet, E.; Flynn, G. and Male, D.
Clinical and Experimental Immunology, 134(3) (pp. 431-441)
Regulation of chemokine receptor expression in human microglia and astrocytes (2003-03)
Flynn, Geraldine; Maru, Seema; Loughlin, Jane; Romero, Ignacio A. and Male, David
Journal of Neuroimmunology, 136(1-2) (pp. 84-93)
Microglia in fetal and adult human brain can be distinguished from other mononuclear phagocytes through their lack of CD163 expression (2003)
Rezaie, Payam and Male, David
Neuroembryology, 2(3) (pp. 130-133)
Distribution and morphology of GFAP-positive astrocytes in the human fetal brain at second trimester (2003)
Rezaie, Payam; Ulfig, Norbert and Male, David
Neuroembryology and Aging, 2(2) (pp. 50-63)
Microglial colonization of the developing mouse brain: the effects of CD11b deletion [poster presentation] (2002-04)
Jeetle, J.K.; Hagger, G.N.; Topps, S.S.; Male, D.K. and Rezaie, P.
Neuropathology and Applied Neurobiology, 28 (p 164)
Motility and ramification of human fetal microglia in culture: an investigation using time-lapse video microscopy and image analysis (2002-03-10)
Rezaie, P.; Trillo-Pazos, G.; Greenwood, J.; Everall, I.P. and Male, D.K.
Experimental Cell Research, 274(1) (pp. 68-82)
Differentiation, ramification and distribution of Microglia within the central nervous system examined (2002)
Rezaie, Payam and Male, David
Neuroembryology and Aging, 1(1) (pp. 29-43)
Mesoglia & microglia: a historical review of the concept of mononuclear phagocytes within the central nervous system (2002)
Rezaie, Payam and Male, David
Journal of the History of the Neurosciences, 11 (pp. 325-374)
Expression of beta-chemokines and chemokine receptors in human fetal astrocyte and microglial co-cultures: potential role of chemokines in the developing CNS (2002)
Rezaie, Payam; Trillo-Pazos, G.; Everall, I.P. and Male, David
Glia, 37(1) (pp. 64-75)
Transplantation of neural stem cells in a rat model of stroke: assessment of short-term graft survival and acute host immunological response (2002)
Modo, Michael; Rezaie, Payam; Heuschling, Paul; Patel, Sara; Male, David K. and Hodges, Helen
Brain Research, 958(1) (pp. 70-82)
Colonisation of the human central nervous system by microglia: the roles of chemokines and vascular adhesion molecules (2001-12-07)
Male, David and Rezaie, Payam
Progress In Brain Research, 132 (pp. 81-93)
Immunology 9th edition (2020-02-19)
Male, David; Peebles, R Stokes and Male, Victoria
ISBN : 978-0-7020-7844-6 | Publisher : Elsevier | Published : London
Immunology: an illustrated outline. 4th edition (2003-10)
ISBN : 0-7234-3336-4 | Publisher : Elsevier | Published : London, UK
Gold nanoparticles for imaging and drug transport to the CNS (2016)
Male, David; Gromnicova, Radka and Mcquaid, Conor
In: Al-Jamal, Khuloud ed. Nanotechnology and the Brain. International Review of Neurobiology (130) (pp. 155-189)
ISBN : 978-0-12-804636-4 | Publisher : Elsevier | Published : London
Immunology (8th ed.) (2012-08)
Male, David; Brostoff, Jonathan; Roth, David and Roitt, Ivan eds.
ISBN : 978-0-323-08058-3 | Publisher : Elsevier | Published : New York
Immunology. 7th edition (2006-04)
Male, David ed.
ISBN : 0-323-03399-7 | Publisher : Elsevier | Published : UK
Toxicity and internalization of polymeric nanoparticles in brain endothelial cells (2017-10-27)
Silva de Abreu, Marcelle; Calpena, Ana C.; Espina, Marta; Garcia, Maria Luisa; Romero, Ignacio A. and Male, David
In : 20th International Symposium on Signal Transduction at the Blood-Brain Barrier (13-15 Sep 2017, Krakow, Poland) (p 19)
Microglial progenitors in the human forebrain during the second trimester [poster presentation] (2004-12)
Rezaie, P.; Male, D.K. and Ulfig, N.
In : 15th Biennial Meeting of the International Society for Developmental Neuroscience (4-7 Aug 2004, Edinburgh, UK)
Colonization of the developing mouse brain by microglial progenitors [poster presentation] (2003)
Corbisiero, V.; Hagger, G.; Topps, S.; Kohsaka, S.; Imai, Y.; Male, D. and Rezaie, P.
In : Third International Symposium on Normal and Abnormal Development of the Human Fetal Brain (13-15 Jun 2003, Zagreb, Croatia)
Microglia in the CD11b knockout mouse [poster presentation] (2002)
Jeetle, J.; Hagger, G.N.; Topps, S.; Male, David and Rezaie, Payam
In : Second International Symposium on Normal and Abnormal Development of the Human Fetal Brain (24-25 May 2002, Institute of Anatomy, University of Rostock, Germany)