Dr Egle SolitoReader in Immunobiology and Education Centre Lead (TMT)Centre: Translational Medicine and TherapeuticsEmail: e.solito@qmul.ac.ukTelephone: +44(0) 20 7882 2117ProfileResearchKey PublicationsSponsorsCollaboratorsNewsTeachingDisclosuresProfileORCID iD: 0000-0001-5279-0049 Egle Solito obtained her PhD at the University of Pavia. After important spells at the Sclavo Research Centre in Siena and Chiron in San Francisco, USA, she was awarded an EU fellowship (Marie Cure-Biotech program 1994) and she joined the Institut Cochin de Genetique Moleculaire, INSERM, in Paris, France. Here she began a fruitful line of research centred on the transcriptional regulation of annexin A1 in cell transformation and differentiation. In January 2000, she moved to Imperial College London, UK, where she continued her long-term interest in annexin A1 biology and started to investigate the role of this protein in the HPA axis and the brain under the sponsorship of the Wellcome Trust (2003-2012), with particular interest in the role it plays in neuroinflammatory and neurodegenerative diseases. Her research spans all aspects of annexin A1 biology and pharmacology ranging from cell biology through to its role in human disease. In October 2006 she was awarded a non-clinical Senior Lectureship in the division of Neuroscience and Mental Health at Imperial College London, UK.In July 2011 she moved to the William Harvey Research Institute (founded by the Nobel Laureate Sir John Vane), Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK within the Centre for Translational Medicine, and Therapeutics.ResearchGroup membersIrina Zalivina (Research Assistant); Anna Poliniewicz (PhD Student) Summary Impact of peripheral inflammation in the central immune response: immune cell trafficking across brain barriersAs the population's average age rapidly increases, so does the incidence of age-associated neurological disease. Hence, there is an urgent need to investigate the mechanisms of senescence and ageing to ameliorate the huge social and economic costs of “ageing welfare”. It was long thought that the brain was protected from systemic inflammation, but growing evidence shows that systemic inflammatory stimuli, such as infection, also trigger a central response. Many pathologies such as Diabetes and hypertension have been linked with cognitive impairment yet studies to date have failed to establish a direct link between traditional vascular risk factors. As the primary interface between the peripheral system and the brain, the blood-brain barrier is a major player in communication between the two compartments, and, alongside the major brain immune cell, the microglia, represent an ideal target system to investigate how peripheral disease and inflammation can affect brain function. We are particularly interested in identifying mechanisms and molecules responsible for the alteration of the BBB as well as the brain immune system. Lab Projects topicsDiet impact on cerebrovascular cell senescence: a risk factor for vascular dementiaAn unhealthy diet, hypertension, and heart disease are the most common factors contributing to or accelerating vascular ageing and are thus major risk factors for brain vascular alterations (e.g. Vascular dementia VaD). With our ageing population, cognitive decline is becoming an important co-morbidity in metabolic disorders. We have shown that young mice fed a high-fat high sugar diet exhibit chronic, low-grade inflammation, blood-brain barrier (BBB) leakage due to tight junction, and basal lamina disruption.This leads to the entry of peripheral immune cells and soluble factors into the brain parenchyma, resulting in glial activation and local inflammation. Most importantly, our data demonstrate that either pharmacological intervention or dietary reversal to a more balanced, healthy diet corrected the BBB leakage via stabilisation of tight junction assembly and the control of tissue inhibitor of metalloproteinase (TIMP-1) expression1. Moreover, we have shown that: 1) older patients with diet-induced type 2 diabetes (T2DM) present with brain vascular leakage, immune cell infiltration, and microglia activation, and 2) serum from T2DM patients significantly disrupt BBB function in vitro (Sheikh et al. FASEB J. 2022). Given these parallels with our murine studies, we hypothesise that consumption of a high-fat high-sugar diet in adult/old age may lead to progressive cerebral damage and cognitive impairment, effectively accelerating the ageing process. Moreover, we will explore whether dietary reversion interventions (as are clinically recommended for T2DM management) can contribute to ameliorating vascular damage, neuroinflammation, and cognitive impairment. In this project we aim to test the hypothesis that high fat-high sugar diet-induced low-grade inflammation, BBB damage, and microglial activation may trigger premature ageing and/or aggravate normal ageing, increasing susceptibility to VaD. Thus, we will further test the hypothesis that the progression of VaD can be controlled by the reversal of the high-fat-high-sugar diet intervention.Pathophysiology of vascular dementia in the heart-brain axisVascular dementia (VaD) is an intracranial vessel disease and the second-most-common type of dementia. Not only cardiovascular risk factors consistently showed a strong association with dementia, but diverse cardiac diseases, including myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), and myocarditis have also been reported to increase the risk of dementia. Coronary artery disease may lead to dementia through its association with brain small vessel disease. Small vessel disease, in turn, disturbs cerebral blood flow (CBF) regulation and perfusion disrupts the blood–brain barrier and leads to an increased susceptibility to neurological insults. Blood vessels provide the vital infrastructure for the delivery of oxygen and essential nutrients throughout the body, and the term “blood-brain barrier” (BBB) is used to describe the unique characteristics of the blood vessels that vascularize the central nervous system. Multiple mediators such as oxidative injury, inflammatory, autoimmune mechanisms, and genetic predisposition have been proposed to play a role in vascular dementia.However, the lack of early diagnosis and therapies highpoint the importance of identifying and controlling immune and vascular factors in heart diseases (e.g., atrial fibrillation) early in life to prevent dementia. This project’s main aim is to identify circulating factors (e.g., fibrinogen, cytokines) that would damage the cerebral endothelium focusing particularly on the BBB and studying the interplay between the immune system and the BBB in VaD. COVID 19 Long-Term Impact on the Brain. A Study at the Interface of the Cerebral Vasculature and Immune System Long COVID, known as ‘post-acute sequelae of COVID-19’, affects multiple body systems including the CNS, and causes prolonged acute and severe symptoms following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At least 65 million people worldwide have long COVID, with more than 651 million cases of COVID-19 documented worldwide. Furthermore, a proportion of long COVID patients develop Myalgic Encephalomyelitis, a chronic autoimmune condition with neurological and immunological symptoms.The WHO has declared COVID-19 an endemic, no longer representing a global health emergency. However, the threat of new variants capable of causing surges in disease remains. It is clear with the lack of diagnostic biomarkers or treatment options; this number will only increase.A main feature of long COVID is neurological symptoms, which develop during or following SARS-CoV-2 infection. Persistent cognitive impairment called COVID-19 ‘brain fog’ is prominent amongst lasting neurological symptoms, characterised by impaired memory and brain functioning. SARS-CoV-2 infection is demonstrated to be linked with a reduction in grey matter thickness of the orbitofrontal cortex, an area of the brain important for cognition, in a landmark UK biobank study. The cerebral vascular system comprises blood vessels essential for brain function, there are approximately 400 miles of capillaries in the brain. The Blood-Brain barrier (BBB), at the capillary level, protects the brain from potentially harmful circulating substances infiltrating into the brain parenchyma. Through post-mortem studies, the mechanisms for brain fog are thought to be that of BBB leakage, inducing activation microglial, the resident innate immune cells in the brain, and the induction of reactivity in astrocytes, triggering the release of damaging reactive oxygen species (ROS). Activated microglia are recognised as a hallmark of neuroinflammation. Neuro-inflammation is also characterised by increased cytokines and chemokines in the cerebrospinal fluid that bathes the brain. Ultimately this leads to neuron loss and neural circuit dysfunction. The AIM of this project is to identify changes in the regulation of BBB components and expression of activated microglia, understand how circulating factor (e.g. cytokines) induced by COVID-19 affects barrier permeability, and define the role of innate/adaptive immune cells in CNS. Key Publications Full list of publications Impact of metabolic disorders on the structural, functional, and immunological integrity of the blood-brain barrier: Therapeutic avenues. Sheikh MH, Errede M, d'Amati A, Khan NQ, Fanti S, Loiola RA, McArthur S, Purvis GSD, O'Riordan CE, Ferorelli D, Dell'Erba A, Kieswich J, Reutelingsperger C, Maiorano E, Yaqoob M, Thiemermann C, Baragetti A, Catapano AL, Norata GD, Marelli-Berg F, Virgintino D, Solito E. FASEB J. 2022 Jan;36(1):e22107. doi: 10.1096/fj.202101297R.PMID: 34939700 The Impact of Ageing on the CNS Immune Response in Alzheimer's Disease. Chee SEJ, Solito E. Front Immunol. 2021 Sep 17;12:738511. doi: 10.3389/fimmu.2021.738511. 2021.PMID: 34603320 Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Cheung KCP, Fanti S, Mauro C, Wang G, Nair AS, Fu H, Angeletti S, Spoto S, Fogolari M, Romano F, Aksentijevic D, Liu W, Li B, Cheng L, Jiang L, Vuononvirta J, Poobalasingam TR, Smith DM, Ciccozzi M, Solito E*, Marelli-Berg FM*. Nat Commun. (I.F. 12) 2020 Jul 17; 11(1):3595. doi: 10.1038/s41467-020-17329 Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Hoyles L, Pontifex MG, Rodriguez-Ramiro I, Anis-Alavi MA, Jelane KS, Snelling T, Solito E, Fonseca S, Carvalho AL, Carding SR, Müller M, Glen RC, Vauzour D, McArthur S. Microbiome. 2021 Nov 27;9(1):235. doi: 10.1186/s40168-021-01181-z.PMID: 34836554 Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology. Ries M, Watts H, Mota BC, Lopez MY, Donat CK, Baxan N, Pickering JA, Chau TW, Semmler A, Gurung B, Aleksynas R, Abelleira-Hervas L, Iqbal SJ, Romero-Molina C, Hernandez-Mir G, d'Amati A, Reutelingsperger C, Goldfinger MH, Gentleman SM, Van Leuven F, Solito E*, Sastre M*. Brain. 2021 Jun 22;144(5):1526-1541. doi: 10.1093/brain/awab050.PMID: 3414807 Identification of an essential endogenous regulator of blood brain barrier integrity: pathological and therapeutic implications. Cristante, E., McArthur, S., Mauro, C., Maggioli, E., Romero, I.A., Wylezinska-Arridge, M., Couraud, PO., Lopez-Tremoleda, J., Christian, H., Weksler, BB., Malaspina, A., Solito, E. Proc Natl Acad Sci USA. 2013 Jan 15;110(3):832-41 Annexin A1: a central player in microglial efferocytosis of apoptotic neurons – implications for neurodegenerative disease, McArthur, S, Cristante, E., Paterno, M., Roncaroli, F., Gillies, GE & Solito E. J. Immunol.185(10):6317-28 (2010) Sponsors Alzheimer Research UK British Heart Foundation (BHF) CollaboratorsInternal Prof. Federica Marelli-Berg Prof. Sian Henson Dr. Simon McArthur External Prof. Magdalena Sastre (Imperial College, London) Prof. Daniela Virgintino (University of Bari School of Medicine, Italy) Dr Helen Stolp (Royal Veterinary College, University of London) Prof. Caroline Menard (Laval University-Canada) Dr Veronica DeRosa (IEOS-CNR-Naples Italy) Dr Nicola Marchi INSERM Montpellier (France) News Silvia Fanti won a poster prize at the 24th international symposium on Blood-Brain Barriers (22-24 September 2022 Bari-Italy), September 2022 Madehaa Sheikh was awarded a Guarantors of Brain travel fellowship to participate in the 13th CVB-2019 Miami FL (USA), June 2019 Madehaa Sheikh was awarded a Guarantors of Brain travel fellowship to participate in the 12th CVB-2017 Melbourne (AU), November 2017 Scientists breach the brain barrier to treat sick patient, BBC News, 10 November 2015 Elisa Maggioli was awarded a BPS travel Fellowship to participate to 8th International Conference on Annexins Maastricht, Netherlands, 8th - 11th Sep 2015. Elisa Maggioli was awarded a Guarantors of Brain travel fellowship to participate in the 11th CVB 2013-Paris (France), 2013 Elisa Maggioli won a poster prize at the London Vascular Biology Forum, December 2013 Restoring the Blood-Brain Barrier, JAMA, 6 February 2013 Annexin A1 (ANXA1): SciBX: Science-Business eXchange - Nature › Journal home › Past Issues › Distillery: Therapeutics Distillery: Therapeutics - Neurology. SciBX 6(3); doi :10.1038/scibx.2013.64. Published online 24 January 2013 Research opens up possibility of therapies to restore blood-brain, Queen Mary University of London (Press Release), 2 January 2013 TeachingProf. Solito teaches at undergraduate and postgraduate (GEP-MRes) levels and supervises BMedSci, MRes and PhD students.• Module Lead BSc in Pharmacology & Innovative Therapeutics (BMD171)• Education Centre Lead• Member of the Education Committee• Member of the International PhD VIVA committeeDisclosures 2017 Dr Solito has received consultancy funds from TRIO-Medicines-Limited. Back to top
Full list of publications Impact of metabolic disorders on the structural, functional, and immunological integrity of the blood-brain barrier: Therapeutic avenues. Sheikh MH, Errede M, d'Amati A, Khan NQ, Fanti S, Loiola RA, McArthur S, Purvis GSD, O'Riordan CE, Ferorelli D, Dell'Erba A, Kieswich J, Reutelingsperger C, Maiorano E, Yaqoob M, Thiemermann C, Baragetti A, Catapano AL, Norata GD, Marelli-Berg F, Virgintino D, Solito E. FASEB J. 2022 Jan;36(1):e22107. doi: 10.1096/fj.202101297R.PMID: 34939700 The Impact of Ageing on the CNS Immune Response in Alzheimer's Disease. Chee SEJ, Solito E. Front Immunol. 2021 Sep 17;12:738511. doi: 10.3389/fimmu.2021.738511. 2021.PMID: 34603320 Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Cheung KCP, Fanti S, Mauro C, Wang G, Nair AS, Fu H, Angeletti S, Spoto S, Fogolari M, Romano F, Aksentijevic D, Liu W, Li B, Cheng L, Jiang L, Vuononvirta J, Poobalasingam TR, Smith DM, Ciccozzi M, Solito E*, Marelli-Berg FM*. Nat Commun. (I.F. 12) 2020 Jul 17; 11(1):3595. doi: 10.1038/s41467-020-17329 Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Hoyles L, Pontifex MG, Rodriguez-Ramiro I, Anis-Alavi MA, Jelane KS, Snelling T, Solito E, Fonseca S, Carvalho AL, Carding SR, Müller M, Glen RC, Vauzour D, McArthur S. Microbiome. 2021 Nov 27;9(1):235. doi: 10.1186/s40168-021-01181-z.PMID: 34836554 Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology. Ries M, Watts H, Mota BC, Lopez MY, Donat CK, Baxan N, Pickering JA, Chau TW, Semmler A, Gurung B, Aleksynas R, Abelleira-Hervas L, Iqbal SJ, Romero-Molina C, Hernandez-Mir G, d'Amati A, Reutelingsperger C, Goldfinger MH, Gentleman SM, Van Leuven F, Solito E*, Sastre M*. Brain. 2021 Jun 22;144(5):1526-1541. doi: 10.1093/brain/awab050.PMID: 3414807 Identification of an essential endogenous regulator of blood brain barrier integrity: pathological and therapeutic implications. Cristante, E., McArthur, S., Mauro, C., Maggioli, E., Romero, I.A., Wylezinska-Arridge, M., Couraud, PO., Lopez-Tremoleda, J., Christian, H., Weksler, BB., Malaspina, A., Solito, E. Proc Natl Acad Sci USA. 2013 Jan 15;110(3):832-41 Annexin A1: a central player in microglial efferocytosis of apoptotic neurons – implications for neurodegenerative disease, McArthur, S, Cristante, E., Paterno, M., Roncaroli, F., Gillies, GE & Solito E. J. Immunol.185(10):6317-28 (2010)