I completed my Ph.D. in Neurological Sciences at McGill University in 2006, studying the role of the insulin-like growth factor-II (IGF-II/M6P) receptor in the regulation of cholinergic neurons.
I then undertook a post-doctoral fellowship at the Tanz Centre for Neurodegenerative Diseases at the University of Toronto, where I conducted experiments using small molecules to prevent the accumulation of the β-amyloid (Aβ) peptide that occurs in the Alzheimer’s disease brain.
I joined the Faculty of Medicine at the University of Southampton in 2009 to study how the blood vessels of the brain change with age and how this impacts on the development of Alzheimer’s disease.
In 2014, I joined the Dept. of Life, Health and Chemical Sciences at the Open University as a Lecturer in Neuroscience to continue working on the vasculature of the ageing brain and how this is impacted by risk factors for Alzheimer's disease and Cerebral Amyloid Angiopathy.
B.Sc., Neuroscience, University of Alberta, Edmonton, Canada (2000)
Ph.D., Neurological Sciences, McGill University, Montreal, Canada (2006)
The aetiology and treatment of Cerebral Amyloid Angiopathy
One of my primary research interests is the pathogenesis of Alzheimer’s disease (AD), with particular focus on cerebral amyloid angiopathy (CAA), the deposition of toxic ß-amyloid (Aß) aggregates that accumulate in the walls of blood vessels in the elderly brain. These vascular Aβ deposits cause vasoconstriction, inhibit angiogenesis and induce endothelial and smooth muscle cell death, leading to microhaemorrhage, stroke and dementia. Despite affecting nearly 30% of all elderly individuals and over 90% of AD patients, this phenomenon is significantly under-researched. Moreover, there are no currently approved therapies for the treatment or prevention of CAA.
My goal is to determine key elements that underlie cerebrovascular ageing and the development of CAA and to uncover physiologic and therapeutic mechanisms by which it can be prevented and treated.
Impact of maternal obesity on the health of the offspring across the lifecourse
I am also interested in the long-term impact of perinatal health and of maternal obesity in particular, on brain function in ageing and the risk of developing AD. Increasing evidence supports a role of maternal obesity in influencing the health of the offpsring, including a predisposition to obesity, metabolic disoders and premature death. However, much less is known about how this affect brain ageing and cogntive function. My goal is detemine how maternal obesity affects cognitive function in the aged offpsring and the epigenetic and cellular mechanisms that underlie these effects.
SDK228 The science of the mind: investigating mental health
SK299 Human Biology
Prof. Roxana Carare, University of Southampton
|Role||Start date||End date||Funding source|
|Co-investigator||01 Oct 2016||30 Sep 2019||Sheffield Teaching Hospitals|
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)
|Role||Start date||End date||Funding source|
|Co-investigator||01 Oct 2015||30 Sep 2018||Sheffield Teaching Hospitals|
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
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)
Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice (2021)
Nizari, Shereen; Wells, Jack A.; Carare, Roxana O.; Romero, Ignacio A. and Hawkes, Cheryl A.
Acta Neuropathologica Communications, 9, Article 12(1)
The evolutionarily conserved long non‐coding RNA LINC00261 drives neuroendocrine prostate cancer proliferation and metastasis via distinct nuclear and cytoplasmic mechanisms (2021)
Mather, Rebecca L.; Parolia, Abhijit; Carson, Sandra E.; Venalainen, Erik; Roig-Carles, David; Jaber, Mustapha; Chu, Shih‐Chun; Alborelli, Ilaria; Wu, Rebecca; Lin, Dong; Nabavi, Noushin; Jachetti, Elena; Colombo, Mario P.; Xue, Hui; Pucci, Perla; Ci, Xinpei; Hawkes, Cheryl; Li, Yinglei; Pandha, Hardev; Ulitsky, Igor; Marconett, Crystal; Quagliata, Luca; Jiang, Wei; Romero, Ignacio A; Wang, Yuzhuo and Crea, Francesco
Molecular Oncology ((Early Access))
LncRNA HORAS5 promotes taxane resistance in castration-resistant prostate cancer via a BCL2A1-dependent mechanism (2020-07)
Pucci, Perla; Venalainen, Erik; Alborelli, Ilaria; Quagliata, Luca; Hawkes, Cheryl; Mather, Rebecca; Romero, Ignacio A; Rigas, Sushila; Wang, Yuzhuo and Crea, Francesco
Epigenomics, 12(13) (pp. 1123-1138)
Cerebrospinal fluid dynamics modulation by diet and cytokines in rats. (2020-02-10)
Alimajstorovic, Zerin; Pascual-Baixauli, Ester; Hawkes, Cheryl A.; Sharrack, Basil; Loughlin, A. Jane; Romero, Ignacio A. and Preston, Jane E.
Fluids and barriers of the CNS, 17, Article 10 (2020)
Knockout of apolipoprotein A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model of Alzheimer's disease (2019-12)
Contu, Laura; Carare, Roxana O. and Hawkes, Cheryl A.
Neuropathology and Applied Neurobiology, 45(7) (pp. 698-714)
3D Reconstruction of the Neurovascular Unit Reveals Differential Loss of Cholinergic Innervation in the Cortex and Hippocampus of the Adult Mouse Brain (2019)
Nizari, Shereen; Carare, Roxana O.; Romero, Ignacio A. and Hawkes, Cheryl A.
Frontiers in Aging Neuroscience, 11, Article 172
Pre- and postnatal high fat feeding differentially affects the structure and integrity of the neurovascular unit of 16-month old male and female mice (2019)
Contu, Laura; Nizari, Shereen; Heath, Christopher J. and Hawkes, Cheryl A.
Frontiers in Neuroscience, 13, Article 1045
Convective infux/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways (2018-07-31)
Albargothy, Nazira J.; Johnston, David A.; MacGregor-Sharp, Matthew; Weller, Roy O.; Verma, Ajay; Hawkes, Cheryl A. and Carare, Roxana O.
Acta Neuropathologica, 136(1) (pp. 139-152)
Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology (2018-04-30)
Horsburgh, Karen; Wardlaw, Joanna M.; van Agtmael, Tom; Allan, Stuart M.; Ashford, Mike L. J.; Bath, Philip M.; Brown, Rosalind; Berwick, Jason; Cader, M. Zameel; Carare, Roxana O.; Davis, John B.; Duncombe, Jessica; Farr, Tracy D.; Fowler, Jill H.; Goense, Jozien; Granata, Alessandra; Hall, Catherine N.; Hainsworth, Atticus H.; Harvey, Adam; Hawkes, Cheryl A.; Joutel, Anne; Kalaria, Rajesh N.; Kehoe, Patrick G.; Lawrence, Catherine B.; Lockhart, Andy; Love, Seth; Macleod, Malcolm R.; Macrae, I Mhairi; Markus, Hugh S.; McCabe, Chris; McColl, Barry W.; Meakin, Paul J.; Miller, Alyson; Nedergaard, Maiken; O'Sullivan, Michael; Quinn, Terry J.; Rajani, Rikesh; Saksida, Lisa M.; Smith, Colin; Smith, Kenneth J.; Touyz, Rhian M.; Trueman, Rebecca C.; Wang, Tao; Williams, Anna; Williams, Steven C. R. and Work, Lorraine M.
Clinical Science, 132(8) (pp. 851-868)
The role of perivascular innervation and neurally mediated vasoreactivity in the pathophysiology of Alzheimer's disease (2017-06)
Nizari, Shereen; Romero, Ignacio A. and Hawkes, Cheryl A.
Clinical Science, 131(12) (pp. 1207-1214)
Vascular basement membranes as pathways for the passage of fluid into and out of the brain (2016-05)
Morris, Alan W. J.; Sharp, Matthew MacGregor; Albargothy, Nazira J.; Fernandes, Rute; Hawkes, Cheryl A.; Verma, Ajay; Weller, Roy O. and Carare, Roxana O.
Acta Neuropathologica, 131(5) (pp. 725-736)
Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet (2016-02-25)
Nizari, Shereen; Carare, Roxana O. and Hawkes, Cheryl A.
Scientific reports, 6, Article 21981
A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain (2016-02-12)
Diem, Alexandra K.; Tan, Mingyi; Bressloff, Neil W.; Hawkes, Cheryl; Morris, Alan W. J.; Weller, Roy O. and Carare, Roxana O.
Frontiers in Aging Neuroscience, 8, Article 18
Does the difference between PART and Alzheimer’s disease lie in the age-related changes in cerebral arteries that trigger the accumulation of Aβ and propagation of tau? (2015-05)
Weller, Roy O.; Hawkes, Cheryl A.; Carare, Roxana O. and Hardy, John
Acta Neuropathologica, 129(5) (pp. 763-766)
Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring (2015-02-10)
Hawkes, Cheryl A.; Gentleman, Steve M.; Nicoll, James A. R. and Carare, Roxana O.
Journal of Pathology, 235(4) (pp. 619-631)
White matter changes in dementia: role of impaired drainage of interstitial fluid (2015-01)
Weller, Roy O.; Hawkes, Cheryl A.; Kalaria, Raj N.; Werring, David J. and Carare, Roxana O.
Brain Pathology, 25(1) (pp. 63-78)
The cerebrovascular basement membrane: Role in the clearance of β-amyloid and cerebral amyloid angiopathy (2014-09-19)
Morris, Alan W. J.; Carare, Roxana O.; Schreiber, Stefanie and Hawkes, Cheryl A.
Frontiers in Aging Neuroscience, 6, Article 251
Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid (2014-08-31)
Maki, Takakuni; Okamoto, Yoko; Carare, Roxana O.; Hase, Yoshiki; Hattori, Yorito; Hawkes, Cheryl A.; Saito, Satoshi; Yamamoto, Yumi; Terasaki, Yasukazu; Ishibashi-Ueda, Hatsue; Taguchi, Akihiko; Takahashi, Ryosuke; Miyakawa, Taihei; Kalaria, Raj N.; Lo, Eng H.; Arai, Ken and Ihara, Masafumi
Annals of Clinical and Translational Neurology, 1(8) (pp. 519-533)
Afferent and efferent immunological pathways of the brain. Anatomy, Function and Failure (2014-02)
Carare, R. O.; Hawkes, C. A. and Weller, R. O.
Brain, Behavior, and Immunity, 36 (pp. 9-14)
Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the chicken and the egg (2014)
Hawkes, Cheryl A.; Carare, Roxana O. and Weller, Roy O.
Acta Neuropathologica, 127(4) (pp. 617-618)
Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy (2014)
Hawkes, Cheryl A.; Jayakody, Nimeshi; Johnston, David A.; Bechmann, Ingo and Carare, Roxana O.
Brain Pathology, 24(4) (pp. 396-403)
Stroke-induced opposite and age-dependent changes of vessel-associated markers in co-morbid transgenic mice with Alzheimer-like alterations (2013-12)
Hawkes, Cheryl A.; Michalski, Dominik; Anders, Rebecca; Nissel, Sabine; Grosche, Jens; Bechmann, Ingo; Carare, Roxana O. and Härtig, Wolfgang
Experimental Neurology, 250 (pp. 270-281)
MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice (2013-12)
Hawkes, C. A.; Shaw, J. E.; Brown, M.; Sampson, A. P.; McLaurin, J. and Carare, R. O.
Neurodegenerative Diseases, 13(1) (pp. 17-23)
Review: Cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy (2013-10)
Carare, R. O.; Hawkes, C. A.; Jeffrey, M.; Kalaria, R. N. and Weller, R. O.
Neuropathology and Applied Neurobiology, 39(6) (pp. 593-611)
Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease (2013-08-09)
Carare, Roxana Octavia; Teeling, Jessica Liesbeth; Hawkes, Cheryl A.; Püntener, Ursula; Weller, Roy O.; Nicoll, James A. R. and Perry, Victor Hugh
Acta neuropathologica communications, 1, Article 48(1)
Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer's disease (2012-10-01)
Dorr, Adrienne; Sahota, Bhupinder; Chinta, Lakshminarayan V.; Brown, Mary E.; Lai, Aaron Y.; Ma, Keran; Hawkes, Cheryl A.; McLaurin, JoAnne and Stefanovic, Bojana
Brain, 135(10) (pp. 3039-3050)
Single-transmembrane domain IGF-II/M6P receptor: potential interaction with G protein and its association with cholesterol-rich membrane domains (2012-10)
Amritraj, Asha; Posse de Chaves, Elena I.; Hawkes, Cheryl; MacDonald, Richard G. and Kar, Satyabrata
Endocrinology, 153(10) (pp. 4784-4798)
In vivo uptake of β-amyloid by non-plaque associated microglia (2012-09-30)
Hawkes, Cheryl A.; Deng, LeHua; Fenili, Daniela; Nitz, Mark and McLaurin, JoAnne
Current Alzheimer Research, 9(8) (pp. 890-901)
Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele (2012-07-25)
Hawkes, Cheryl A.; Sullivan, Patrick M.; Hands, Sarah; Weller, Roy O.; Nicoll, James A. R. and Carare, Roxana O.
PLoS ONE, 7, Article e41636(7)
S1P is associated with protection in human and experimental cerebral malaria (2011-07)
Finney, Constance A. M.; Hawkes, Cheryl A.; Kain, Dylan C.; Dhabangi, Aggrey; Musoke, Charles; Cserti-Gazdewich, Christine; Oravecz, Tamas; Liles, W. Conrad and Kain, Kevin C.
Molecular Medicine, 17(7-8) (pp. 717-725)
Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy (2011)
Hawkes, Cheryl A.; Härtig, Wolfgang; Kacza, Johannes; Schliebs, Reinhard; Weller, Roy O.; Nicoll, James A. and Carare, Roxana O.
Acta Neuropathologica, 121(4) (pp. 431-443)
Small molecule β-amyloid inhibitors that stabilize protofibrillar structures in vitro improve cognition and pathology in a mouse model of Alzheimer's disease (2010-01-18)
Hawkes, Cheryl A.; Deng, Le-Hua; Shaw, James E.; Nitz, Mark and McLaurin, JoAnne
European Journal of Neuroscience, 31(2) (pp. 203-213)
Small molecule inhibitors of Aβ-aggregation and neurotoxicity (2009-03-19)
Hawkes, Cheryl A.; Ng, Vivian and McLaurin, JoAnne
Drug Development Research, 70(2) (pp. 111-124)
Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy (2009-01-27)
Hawkes, Cheryl and McLaurin, JoAnne
Proceedings of the National Academy of Sciences of the United States of America, 106(4) (pp. 1261-1266)
Altered levels and distribution of IGF-II/M6P receptor and lysosomal enzymes in mutant APP and APP + PS1 transgenic mouse brains (2009-01)
Amritraj, A.; Hawkes, C.; Phinney, A. L.; Mount, H. T.; Scott, C. D.; Westaway, D. and Kar, S.
Neurobiology of Aging, 30(1) (pp. 54-70)
Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation (2008-08-01)
Sun, Yedi; Zhang, Guohau; Hawkes, Cheryl A.; Shaw, James E.; McLaurin, JoAnne and Nitz, Mark
Bioorganic & Medicinal Chemistry, 16(15) (pp. 7177-7184)
Clinical immunotherapy trials in Alzheimer's disease (2008)
Hawkes, Cheryl A. and McLaurin, JoAnne
Drug Discovery Today: Therapeutic Strategies, 5(3) (pp. 177-183)
Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria (2007-12)
Lovegrove, Fiona E.; Gharib, Sina A.; Patel, Samir N.; Hawkes, Cheryl A.; Kain, Kevin C. and Liles, W. Conrad
American Journal of Pathology, 171(6) (pp. 1894-1903)
Immunotherapy as treatment for Alzheimer's disease (2007-11)
Hawkes, Cheryl A. and McLaurin, JoAnne
Expert Review of Neurotherapeutics, 7(11) (pp. 1535-1548)
Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor: functional interaction and relevance to cell signaling (2007-06)
Hawkes, C.; Amritraj, A.; MacDonald, R. G.; Jhamandas, J. H. and Kar, S.
Molecular Neurobiology, 35(3) (pp. 329-345)
Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the IGF2-deficient adult mouse brain (2007)
Dikkes, P.; Hawkes, C.; Kar, S. and Lopez, M. F.
Brain Research, 1131(1) (pp. 77-87)
Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal-lysosomal markers in surviving neurons after 192-IgG-saporin administrations into the adult rat brain (2006-10)
Hawkes, Cheryl; Kabogo, Doreen; Amritraj, Asha and Kar, Satyabrata
American Journal of Pathology, 169(4) (pp. 1140-1154)
Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model (2006-07)
McLaurin, JoAnne; Kierstead, Meredith E.; Brown, Mary E.; Hawkes, Cheryl A.; Lambermon, Mark H. L.; Phinney, Amie L.; Darabie, Audrey A.; Cousins, Julian E.; French, Janet E.; Lan, Melissa F.; Chen, Fusheng; Wong, Sydney S.N.; Mount, Howard T. J.; Fraser, Paul E.; Westaway, David and St. George-Hyslop, Peter
Nature Medicine, 12(7) (pp. 801-808)
Cyclin-dependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3β (2006-03-14)
Li, Tong; Hawkes, Cheryl; Quereshi, Hamid Y.; Kar, Satyabrata and Paudel, Hemant K.
Biochemistry, 45(10) (pp. 3134-3145)
Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology (2006-02)
Kar, S.; Poirier, J.; Guevara, J.; Dea, D.; Hawkes, C.; Robitaille, Y. and Quirion, R.
Neurobiology of Aging, 27(2) (pp. 199-210)
Single transmembrane domain insulin-like growth factor-II/mannose-6- phosphate receptor regulates central cholinergic function by activating a G-protein-sensitive, protein kinase C-dependent pathway (2006-01-11)
Hawkes, Cheryl; Jhamandas, Jack H.; Harris, Kim H.; Fu, Wen; MacDonald, Richard G. and Kar, Satyabrata
Journal of Neuroscience, 26(2) (pp. 585-596)
Selective loss of basal forebrain cholinergic neurons by 192 IgG-saporin is associated with decreased phosphorylation of Ser9 glycogen synthase kinase-3β (2005)
Hawkes, Cheryl; Jhamandas, J.H. and Kar, S.
Journal of Neurochemistry, 95(1) (pp. 263-272)
The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system (2004-03)
Hawkes, Cheryl and Kar, S.
Brain Research Reviews, 44(2-3) (pp. 117-140)
Insulin-like growth factor-II/mannose-6-phosphate receptor: Widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype (2003-03-31)
Hawkes, Cheryl and Kar, Satyabrata
Journal of Comparative Neurology, 458(2) (pp. 113-127)
Insulin-like growth factor-II/Mannose-6-phosphate receptor in the spinal cord and dorsal root ganglia of the adult rat (2002-01)
Hawkes, Cheryl and Kar, S.
European Journal of Neuroscience, 15(1) (pp. 33-39)
Analysis of receptor localization in the central nervous system using in vitro and in vivo receptor autoradiography (2007)
Kar, S. and Hawkes, C.
In: Lajtha, Abel; Baker, Glenn; Dunn, Susan and Holt, Andrew eds. Handbook of Neurochemistry and Molecular Neurobiology: Practical Neurochemistry Methods (pp. 275-292)
ISBN : 978-0-387-30401-4 | Publisher : Springer
The Case For Cholinesterase Inhibition To Modify Neurodegenerative Diseases Through The Intramural Periarterial Drainage Of The Cns (IPAD) (2019-07)
Rich, Steven A.; Carare, Roxana O.; Snyder, Peter J. and Hawkes, Cheryl A.
In : Alzheimer's Association International Conference 2019 (14-18 Jul 2019, Los Angeles, California) (P926)