Prf Ignacio Romero Romero

Professor In Cellular Neuroscience

School of Life, Health & Chemical Sciences

nacho.romero@open.ac.uk

Biography

Professional biography

I am a cell biologist with research and teaching interests in blood-brain barrier physiology and pathology and in neuroimmunology.

Research interests

Overview: My research interests focus on the function of cerebral blood vessels in health and disease. In particular, I am interested in the pathogenic mechanisms of blood-brain barrier (BBB) dysfunction in disorders of the central nervous system (CNS) such as multiple sclerosis (MS) and Alzheimer’s disease (AD). I have currently focused my research strategy in identifying the molecular mechanisms mediating abnormal increases in BBB permeability and in leukocyte migration, which ultimately contribute to neuronal death. My research has applications not only as a means to identify potential therapeutic targets for CNS pathologies but also to provide a basis to enhance drug delivery to the CNS. In order to address these questions, my research group uses cell and molecular techniques applied to cultured human brain endothelium and astrocytes and in vivo animal models of disease.

https://www.researchgate.net/profile/Ignacio_Romero2

Current Research Projects:

Development and characterization of in vitro human blood-brain barrier models
Transcriptional and post-trancriptional control of brain endothelial phenotype in neuroinflammation and ageing, in particular microRNAs and lncRNAs
Identification of non-antibody binding domains targeting brain-endothelial cell surface moieties as drug transport carriers

Teaching interests

Overview: Open University teaching is based upon distance learning, with students studying core teaching materials designed, produced and led by academics. Our modules are studied for both standard undergraduate purposes and for CPD by professional scientists across the world. Our module materials are produced by teams of academics and production media specialists and teaching is directly provided in small groups by our specialised teams of associated lecturers. Modules are taken by a number of students ranging from ~100 (e.g. practical modules) to ~1,500 (e.g. biological psychology) every presentation. Assessment is in the form of tutor- (TMA) or computer-marked (CMA) assessments and examinable components (ECA). My main teaching area reflects my research field of cell and molecular neurobiology.

Roles in modules I have contributed to

Module Team Chair: Level 3 The molecular basis of human disease (15 points) (2009-2012) and Level 2 Human Biology (30 points) (2004-2005): As a module chair I worked on overseeing the presentation of the which includes the delivery of assessment to students, chairing Exam Boards, Standardisation and Awards meetings and organizing script marking.

Author of distance teaching material (text and activities) and assessment: Level 3 Infectious Disease, author 2 chapters and computer-marked assessment; Level 1 Understanding Cancers, Author 5 chapters, Web-based CD-ROM activities, and computer-marked continuous and examinable assessment; Level 3 The molecular basis of human disease, author 3 chapters CD-ROM based Experimental Investigation and Activities; Level 2 Biological psychology: Exploring the Brain, author 2 chapters, Web-based ‘Exploring the Brain’ CD-ROM, tutor-marked continuous and examinable assessment; Level 3 Molecular and Cell Biology, author 2 chapters, CD-ROM based Activities and tutor-marked continuous and examinable assessment.

Design of Laboratory Practical Experimentation: Level 3 The molecular basis of human disease: (15 points) (2006-2012). A laboratory based module studied by 120 students per year, focussed on the relationship between human genetic variation and susceptibility to HIV1 infection. Practical teaching covered area of PCR and western blot analysis.

Design of Virtual Experimentation: Level 2 Practical Science Drug metabolism and genetic variation (30 points) (2010-present); Level 3 Plants, Pigments and Light (15 points) (2004-2005); Level 3 Fat – the physiology of adipose tissue (15 points) (2004-2005); Level 3 The molecular basis of human disease: (15 points) (2006-2012).

Extra-curricular Distance Teaching: Academic Editor of Communicable Diseases module and workshop facilitator for the Open University’s Health Education and Training (HEAT) Programme in collaboration with the Ethiopian Federal Ministry of Health (2011), aimed at training frontline healthcare workers in Sub-Saharan Africa.

Projects

Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics Into The Brain Acronym

DISCOVERY AND CHARACTERISATION OF BLOOD-BRAIN BARRIER TARGETS AND TRANSPORT MECHANISMS FOR BRAIN DELIVERY OF THERAPEUTICS TO TREAT NEURODEGENERATIVE & METABOLIC DISEASES

Investigation into the molecular mechanisms underlying idiopathic intracranial hypertension (IIH)

Investigation into the molecular mechanisms underlying idiopathic intracranial hypertension Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by increased intracranial pressure in the absence of a tumour or other diseases. IIH affects primarily pre-menopausal obese women but the contribution of reproductive hormones and/or obesity to the pathogenesis of this disease is unknown. Indeed, as its name implies, its aetiology remains elusive although a possible role for inflammatory mediators has been suggested. From a physiological point of view, raised intracranial pressure may be the result of increased cerebrospinal fluid (CSF) secretion, decreased CSF drainage or a combination of both factors. The objectives for this project are: Year 1. To determine transcriptomic and microRNA changes in choroid plexus of female control rats and rats fed a high-fat diet and in young and old female rats. Years 2 and 3. First, to establish an in vitro rat model of the blood-CSF barrier and, second, to select candidates from the transcriptomic/microRNA analysis that are differentially regulated and investigate their effects on the secretory and transport activity of rat and/or human choroid plexus epithelium (both cell lines and primary cultures)

Long non-coding RNAs implicated in neuroendocrine prostate cancer initiation and progression: novel therapeutic targets for an incurable disease.

Neuroendocrine prostate cancer (NEPC) is the most aggressive prostate cancer type. This disease is resistant to all available therapies, highly metastatic and rapidly fatal. We believe that the elucidation of NEPC-driving pathways could pave the way for the development of effective therapies. Long non-coding RNAs (lncRNAs) are a vast and mostly uncharted region of the human transcriptome. Despite their emerging role in cancer biology, no study has assessed the relevance of lncRNAs in NEPC development. Our collaborator Dr. Wang (BC Cancer Agency) has developed a unique collection of patient-derived prostate cancer models. This collection includes the first-in-field model of transdifferentiation from prostatic adenocarcinoma to NEPC. Aims. We propose to study the role of lncRNAs in NEPC development. The objectives of this study are to determine: 1) whether transcriptomic profiles of lncRNAs in PCa pre-clinical models can elucidate the mechanisms of NEPC development. 2) if selected lncRNAs are promising therapeutic targets for NEPC. Accordingly, our specific aims will be: AIM 1: Identification, functional and clinical characterization of NEPC-driving lncRNAs. AIM 2: Development of innovative therapeutic strategies to prevent NEPC development. At the end of this project, we hope to shed new light on an incurable disease, and to identify viable therapeutic targets, which will be investigated in future translational and clinical studies.

BtRAIN (Brain Barriers training) - To understand the brain barriers

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/

Role of microRNAs in endothelial-derived extracellular vesicles on leukocyte migration across the blood-brain barrier

Intercellular communication between immune cells and tissue-resident cells is essential to coordinate an effective immune response and involves both cell-contact dependent and independent processes that ensure the transfer of information between bystander and distant cells. There is a rapidly growing body of evidence on the pivotal role of extracellular vesicles (EVs) in cell communication and these structures are emerging as important mediators for immune modulation upon delivery of their molecular cargo. In the last decade, EVs have been shown to be efficient carriers of genetic information, including microRNAs, that can be transferred between cells and regulate gene expression and function on the recipient cell. However, little is known about regulation of cellular function by EVs at the blood-brain barrier (BBB), the main route of entry of immune cells into the central nervous system (CNS), in pathological conditions. We have recently shown that EVs isolated from MS patients induce blood-brain barrier dysfunction, characterised by leakiness of the barrier, in a human culture model (1) and that the microRNA profile of brain endothelium undergoes profound changes in inflammation (2,3). Thus, the proposed project will investigate the role of microRNAs secreted in EVs in activation of brain endothelium and subsequent leukocyte migration. In year 1, the miroRNA profile of EVs released by cultured human brain endothelium in inflammatory conditions and in plasma of MS patients will be determined. In year 2, the effects of endothelial-derived and MS plasma-derived EVs on leukocyte adhesion, both leukocyte cell lines and peripheral blood mononuclear cells, under flow will be investigated. In year 3, specific microRNAs will be knocked-down in cultured human brain endothelium prior to EV collection and subsequent effects on leukocyte adhesion will be investigated

Investigation Into The Molecular Mechanisms Underlying Idiopathic Intracranial Hypertension (IIH) - Four Months Stipend Payment extension

IIH is a neurological condition characterized by increased intracranial pressure in the absence of a tumor or other diseases but whose cause remains elusive. A possible role for leptin and inflammatory mediators such as CCL2 has been suggested. The objectives for this project are: 1. To determine, the effect of these inflammatory mediators on cerebrospinal fluid (CSF) secretion and drainage 2. To determine the role of sex and high-fat diet on CSF secretion and drainage. 3. to establish an in vitro human model of the blood-CSF barrier and to determine , using transcriptomic analysis, the effect of inflammatory mediators on gene profile of cultures of human choroid plexus epithelium . These results may help identify potential therapeutic molecular targets for IIH