Institut national de la santé et de la recherche médicale (INSERM)

Inserm
Inserm is the leading scientific and technological academic institute in France devoted to biomedical research and public health, with approximately 320 departments and 6000 researchers. Inserm, which holds a portfolio of 1279 patent families (with > 25% licensed patents), ranks 1st among European academic institutions in patent filling for biomedical research.
The Department of Genetics and Pathogenesis of Cerebrovascular Diseases is part of Inserm. The department is committed to advance diagnosis, research and treatment options in inherited diseases affecting the brain vessels. One major focus of our research is on pathogenic mechanisms of monogenic form of cerebral SVDs. Our methodological expertise is in molecular, proteomic, structural and functional analysis of brain microvessels in genetically engineered mouse models using ex vivo and in vivo approaches. The department has a longstanding interest in CADASIL, the most frequent inherited SVD caused by dominant mutations in the NOTCH3 receptor, and has produced some of the seminal work in this field.

Roles and tasks of INSERM in SVDs@target

Inserm will lead WP3 (Microvascular matrisome and vascular integrity). In this WP, Inserm will identify changes in the extracellular matrix of brain microvessels in SVDs, shared by multiple SVDs as well as changes specific for individual SVDs and will determine whether and how these changes contribute to microvessel dysfunction and brain lesions.  Inserm will also contribute to WP2 (analysis of blood brain barrier integrity in mouse models of monogenic forms of SVD), WP4 (proteomic analysis of vascular basement membranes), and WP5 (genetic manipulation of selected targets in the mouse for validation through interventions and in vivo analysis of cerebrovascular function).

 

 

 

Key staff

Prof. Anne Joutel

Research Director

 

Major field of research: SVDs; specific expertise in genetics, mouse models of SVDs, biochemistry, proteomics, electron microscopy and cerebrovascular physiology

 

Prof. Joutel has a longstanding interest in monogenic forms of SVDs and has produced seminal work on CADASIL and cerebrovascular function of Notch3 receptor. Her lab originally identified the Notch3 gene and delineated its role in CADASIL (Joutel et al. Nature 1995; Joutel et al. Lancet 1997). Her lab has developed and characterized multiple Notch3-related mouse models, including the first (and only) mouse model recapitulating most of the key features of CADASIL, as well as conditional and inducible mouse models of activation and inactivation of Notch in SMCs. She has initiated with Prof. Nelson (University of Vermont) a transatlantic research network on the pathogenesis of SVDs funded by the Fondation Leducq (website).

 

Prof. Joutel is a work package leader (WP3) in SVDs@target.

 

SVD@target team at INSERM

Dr. Monara Angelim
Senior Post-Doc


I am a Postdoc in Joutel's team, at IPNP (Paris). After my PhD in Neuroscience, I joined the research group to collaborate in CADASIL project. Our aiming is better characterize the accumulation of Notch3ECD receptor in the brain vessels of CADASIL mouse models. For that, techniques of immunohistofluorescence, electronmicroscopy, confocal/AiryScan imaging and cell  quantification have been used.




Dr. Julien Ratelade
Senior Post-Doc


Dr. Hussein Kalakech
Junior Post-Doc


Mrs. Valerié Domenga
Engineer
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Tweets by SVDS@target

Publications with PubMed ID

Authors: Sleight E, Stringer MS, Marshall I, Wardlaw JM, Thrippleton MJ

Frontiers in physiology. 2021;12:643468

PMID: 33716793    Open Access: PMC7947694

Authors: Valdés Hernández MDC, Grimsley-Moore T, Chappell FM, Thrippleton MJ, Armitage PA, Sakka E, Makin S, Wardlaw JM

Frontiers in neurology. 2021;12:634460

PMID: 33732208    Open Access: PMC7956970

Authors: Webb AJS, Lawson A, Mazzucco S, Li L, Rothwell PM, Oxford Vascular Study Phenotyped Cohort.

Stroke. 2021 Apr;52(4):1330-1338

PMID: 33588593

Authors: Harshfield EL, Georgakis MK, Malik R, Dichgans M, Markus HS

Stroke. 2021 Mar;52(3):931-936

PMID: 33535786    Open Access: PMC7903981

Authors: Liu G, Mestre H, Sweeney AM, Sun Q, Weikop P, Du T, Nedergaard M

Cell reports. 2020 Dec 22;33(12):108524

PMID: 33357428

Authors: van den Brink H, Weaver NA, Biessels GJ

Case reports in neurology. 2020 Sep-Dec;12(3):416-421

PMID: 33362520    Open Access: PMC7747080

Authors: Valdés Hernández MDC, Smith K, Bastin ME, Nicole Amft E, Ralston SH, Wardlaw JM, Wiseman SJ

Lupus. 2021 Feb;30(2):285-298

PMID: 33307988    Open Access: PMC7854491

Authors: Webb AJS, Lawson A, Wartolowska K, Mazzucco S, Rothwell PM

Hypertension (Dallas, Tex. : 1979). 2021 Jan;77(1):193-201

PMID: 33249860    Open Access: PMC7720874

Authors: Biessels GJ

Stroke. 2020 Dec;51(12):3487-3488

PMID: 33148147

Authors: Hamilton OKL, Backhouse EV, Janssen E, Jochems ACC, Maher C, Ritakari TE, Stevenson AJ, Xia L, Deary IJ, Wardlaw JM

Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020 Nov 13;

PMID: 33185327

Authors: Webb AJ, Lawson A, Mazzucco S, Li L, Rothwell PM

International journal of stroke : official journal of the International Stroke Society. 2020 Nov 9;:1747493020971905

PMID: 33167788

Authors: Webb AJ, Lawson A, Li L, Mazzucco S, Rothwell PM, Oxford Vascular Study Phenotyped Cohort.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2020 Nov 5;:271678X20969984

PMID: 33153374

Authors: Clancy U, Appleton JP, Arteaga C, Doubal FN, Bath PM, Wardlaw JM

Chinese medical journal. 2020 Oct 6;134(2):127-142

PMID: 33118960    Open Access: PMC7817338

Authors: Giannetto M, Xia M, Stæger FF, Metcalfe T, Vinitsky HS, Dang JAML, Xavier ALR, Kress BT, Nedergaard M, Hablitz LM

Scientific reports. 2020 Sep 30;10(1):16073

PMID: 32999319    Open Access: PMC7528110

Authors: Cleary CM, Moreira TS, Takakura AC, Nelson MT, Longden TA, Mulkey DK

eLife. 2020 Sep 14;9

PMID: 32924935    Open Access: PMC7521922

Authors: Stringer MS, Lee H, Huuskonen MT, MacIntosh BJ, Brown R, Montagne A, Atwi S, Ramirez J, Jansen MA, Marshall I, Black SE, Zlokovic BV, Benveniste H, Wardlaw JM

Translational stroke research. 2021 Feb;12(1):15-30

PMID: 32936435    Open Access: PMC7803876

Authors: Elschot EP, Backes WH, Postma AA, van Oostenbrugge RJ, Staals J, Rouhl RPW, Jansen JFA

Investigative radiology. 2021 Jan;56(1):10-19

PMID: 32932377

Authors: Hablitz LM, Plá V, Giannetto M, Vinitsky HS, Stæger FF, Metcalfe T, Nguyen R, Benrais A, Nedergaard M

Nature communications. 2020 Sep 2;11(1):4411

PMID: 32879313    Open Access: PMC7468152

Authors: Kerkhofs D, van Hagen BT, Milanova IV, Schell KJ, van Essen H, Wijnands E, Goossens P, Blankesteijn WM, Unger T, Prickaerts J, Biessen EA, van Oostenbrugge RJ, Foulquier S

Theranostics. 2020;10(21):9512-9527

PMID: 32863942    Open Access: PMC7449902

Authors: Lee YK, Rothwell PM, Payne SJ, Webb AJS

Physiological measurement. 2020 Oct 6;41(9):095002

PMID: 32764198    Open Access: PMC7116588

Authors: Gill D, Georgakis MK, Zuber V, Karhunen V, Burgess S, Malik R, Dichgans M

Journal of the American Heart Association. 2020 Jul 21;9(14):e016773

PMID: 32627641    Open Access: PMC7660704

Authors: Georgakis MK, Gill D, Malik R, Protogerou AD, Webb AJS, Dichgans M

Hypertension (Dallas, Tex. : 1979). 2020 Sep;76(3):953-961

PMID: 32623925    Open Access: PMC7418931

Authors: Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, Roth S, Megens RTA, Straub T, Thomas K, Yan G, Schneider M, Ziesch N, Tiedt S, Silvestre-Roig C, Braster Q, Huang Y, Schneider M, Malik R, Haffner C, Liesz A, Soehnlein O, Bernhagen J, Dichgans M

Circulation research. 2020 Aug 28;127(6):811-823

PMID: 32546048

Authors: Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M

Neurology. 2020 Jul 28;95(4):e353-e361

PMID: 32611631    Open Access: PMC7455321

Authors: Mestre H, Mori Y, Nedergaard M

Trends in neurosciences. 2020 Jul;43(7):458-466

PMID: 32423764    Open Access: PMC7331945

Authors: Biessels GJ, Nobili F, Teunissen CE, Simó R, Scheltens P

The Lancet. Neurology. 2020 Aug;19(8):699-710

PMID: 32445622

Authors: Blair GW, Thrippleton MJ, Shi Y, Hamilton I, Stringer M, Chappell F, Dickie DA, Andrews P, Marshall I, Doubal FN, Wardlaw JM

Neurology. 2020 May 26;94(21):e2258-e2269

PMID: 32366534    Open Access: PMC7357294

Authors: Ratelade J, Klug NR, Lombardi D, Angelim MKSC, Dabertrand F, Domenga-Denier V, Al-Shahi Salman R, Smith C, Gerbeau JF, Nelson MT, Joutel A

Circulation. 2020 Jun 23;141(25):2078-2094

PMID: 32183562    Open Access: PMC7311305

Authors: Li Q, Aalling NN, Förstera B, Ertürk A, Nedergaard M, Møllgård K, Xavier ALR

Fluids and barriers of the CNS. 2020 Feb 11;17(1):15

PMID: 32046744    Open Access: PMC7014736

Authors: Georgakis MK, Malik R, Anderson CD, Parhofer KG, Hopewell JC, Dichgans M

Brain : a journal of neurology. 2020 Feb 1;143(2):597-610

PMID: 31968102    Open Access: PMC7009571

Authors: Sloots JJ, Biessels GJ, Zwanenburg JJM

NeuroImage. 2020 Apr 15;210:116581

PMID: 31982580

Authors: Mestre H, Du T, Sweeney AM, Liu G, Samson AJ, Peng W, Mortensen KN, Stæger FF, Bork PAR, Bashford L, Toro ER, Tithof J, Kelley DH, Thomas JH, Hjorth PG, Martens EA, Mehta RI, Solis O, Blinder P, Kleinfeld D, Hirase H, Mori Y, Nedergaard M

Science (New York, N.Y.). 2020 Mar 13;367(6483)

PMID: 32001524    Open Access: PMC7375109

Authors: Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M

Nature communications. 2019 Dec 20;10(1):5819

PMID: 31862893    Open Access: PMC6925280