Adénovirus : Récepteurs, Trafic Intracellulaire et Vectorologie

Eric J Kremer

Projets de recherche

For the last 20 years, the Kremer lab has had a broad interest in adenovirus biology. Adenoviruses are nonenveloped, double-stranded DNA pathogens with a genome size of 28 – 42 kb. To date, ~70 human and > 150 nonhuman adenovirus types have been described. We focus on human and canine adenoviruses (CAV-2) vectors.

OUR PRINCIPLE AREAS OF INTEREST ARE:

1.Understanding the function of CAR, the coxsackievirus adenovirus receptor, in the healthy and disease brain, and during adenovirus trafficking.

As the name suggests, CAR was originally identified as an attachment molecule for coxsackie B viruses and some adenoviruses, including canine adenovirus type 2 (CAV-2) vectors, whose transduction efficacy is CAR dependent. CAR is a single-pass transmembrane protein belonging to the CTX subfamily of the Ig-super family. CAR function is best characterized in epithelial cells where it participates to the maintenance of tight junctions. Although a role for CAR in brain development has been hypothesized and a function in regulating axonal growth reported, its role in the adult brain is largely uncharacterized. In this context, understanding CAR’s biological function, as well as the impact of its loss of function and distribution in the CNS is indispensable for both fundamental and applied neurobiology studies.

Figure 1. Mouse hippocampal neurons at day in vitro 15 (DIV 15). Cells were labelled for mouse coxsackie- and adenovirus receptor using a goat anti-mCXADR (R&D systems) detected with a donkey anti-goat Alexa 488 and a rabbit anti-CAR (gift from Joseph Zabner) detected with an donkey anti-rabbit Alexa 647. Nucleus were stained using DAPI (blue). Images were acquired using Leica SP5 confocal microscope with 40X 1.4 oil objectives. Serial Z-plan were recorded and images represent z-projection of all 34 plan acquire. (yellow image)

Images represent mouse hippocampal neurons at day in vitro 7 (DIV 7). Cells were labelled for mouse coxsackie- and adenovirus receptor using a rabbit anti-mCAR (Bethyl) detected with a donkey anti-mouse Alexa 555 and a mouse anti-RNA Pol II H5 (Abcam) detected with an donkey anti-mouse Alexa 488. Nucleus were stained using DAPI (blue). Images were acquired using Leica SP5 confocal microscope with 40X 1.4 oil objectives. Serial Z-plan were recorded and images represent overlay from different plan. Images were pseudo-colored CAR in magenta, RNA pol in cyan and DAPI in yellow.

2.Understanding how mononuclear phagocytes, in particular dendritic cells, process and respond to immune-complexed adenoviruses (IC-Ad)

The nearly ubiquitous presence of anti-adenovirus antibodies and memory T cells is due to recurrent and cross-reacting adenovirus infections during childhood. Thus, when Ad-based vectors are used in a host with memory immunity this creates an environment close to a secondary infection in the clinic.

How do IC-Ads and other host factors impact the maturation of antigen-presenting cells (APC)? Our underlying questions encompass the entry and signaling pathways and how the IC-Ads traffic in APC. In our studies we use human dendritic cells to study the interaction of IC-HAd5 and innate immune sensors. Dendritic cells are the major APC in blood and tissue and play a pivotal role in the sensing of infection and activation and re-activation of the adaptive immune response.

IC-Ads triggers several innate immune sensors and induce DC maturation (the virus alone is far less potent). Our aim is to understand the interactions of the IC-Ads during the initial activation and death of DC. Our studies contribute to both fundamental and applied questions in adenovirus biology, vaccination and gene therapy.

Figure 2. IC-HAdV trafficking and cellular events leading to pyroptotic dendritic cell death.

IC-HAdV are taken up via FcγR-mediated endocytosis and fuse with TLR9⁺ endolysosomal vesicles because of NAb-dependent capsid stabilization at endosomal pH. At the more acidic pH in lysosome-like vesicles, IC-HAdV begin to disassemble and to release viral DNA, membrane lytic protein VI, and cellular components. TLR9 engagement induces MyD88-NF-κB-dependent de novo expression of TNF and pro-IL-1β. During vesicular DNA sensing, protein VI release from the capsid leads to endolysosomal membrane lysis and IC-HAdV gain access to the cytosol. The cytosolic inflammasome sensor AIM2 interacts with the HAdV-C5 genome and induces inflammasome assembly and activation of caspase 1, and downstream cleavage of pro-IL-1 and GSDMD. Together this leads to pyroptosis of MoDCs.

Le sous-groupe est composé de Florence Rage, Johann Soret, Pauline Duc et Audrey Moisan

Étude des mécanismes moléculaires de l’atrophie spinale (SMA)

BOURSES DE MASTER INTERDISCIPLINAIRES – IGMM (cnrs.fr)

L’Amyotrophie spinale (SMA) est une maladie génétique rare dont l‘incidence est d’environ 1 pour 6000 naissances. Elle représente la deuxième cause de mort infantile. Cette maladie se caractérise par la mort des motoneurones (MN) alpha de la moelle épinière entrainant une atrophie musculaire sévère allant jusqu’à la paralysie. La mutation et/ou délétion du gène SMN1 entraine une expression très faible de la protéine SMN affectant ainsi le métabolisme des ARN et en particulier leur épissage. Afin d’expliquer la grande vulnérabilité des neurones, un rôle plus spécifique sur le transport des ARNm dans l’axone et leur traduction locale pendant le développement et le maintien de la jonction neuromusculaire (NMJ) a été suggéré.

Notre projet vise à comprendre ces mécanismes dans un modèle humain de motoneurones issus de cellules souches pluripotentes (iPSC) d’individus sains ou de patients atteints de SMA. Ainsi nous récapitulons la maladie et étudions :

Les défauts d’épissage dans les cellules pathologiques.
Le transport et la traduction locale des ARNm dans l’axone de motoneurones sains et malades en utilisant des techniques de détection de molécules uniques (smFISH) ou des systèmes de marquage (MS2 ou SunTag) intégrés par CRISPR-Cas9 dans les gènes d’intérêt pour une visualisation en cellules vivantes.
L’interactome de SMN dans des MN et des muscles sains et SMA en combinant CRISPR-Cas9 et BioID.
La fonctionnalité de la NMJ mature au cours de son développement et de son maintien par l’utilisation d’un système compartimentalisé de chambres micro-fluidiques équipées d’une plateforme de microélectrodes en collaboration avec B. Charlot (IES) et Gilles Carnac (Phymedexp)
Enfin, en collaboration avec Eran Perlson (Université de Tel Aviv, Israël), nous développons une plateforme de culture à 24 chambres microfluidiques, combinées à des MEA, dans le but de récapituler des JNM humaines de patients SMA et ALS et d’effectuer des criblages de drogues avec une approche de type médecine personnalisée.

A- Schéma représentant la plateforme microfluidique, équipée de MEA, développée par le groupe afin de reconstituer une jonction neuromusculaire humaine, mature et fonctionnelle, et d’enregistrer son activité électrique (Duc et al., 2021). B- Schéma de l’efficacité de l’épissage dans un modèle murin, dépendante du score U12-U2 (Jacquier et al., 2022).

Membres

Team leader

Eric KREMER

Directeur de Recherche CE

Phone : (+33) 04 34 35 96 72

Room : 217

Florence RAGE

Chercheur DR2

Phone : (+33) 04 34 35 96 42

Room : RDC 04

Marina LAVIGNE

IE-Recherche

Phone : +33 (0)4 34 35 96 75

Room : 217

Bertrand BEUCHER

IR-Recherche

Phone : +33 (0)4 34 35 96 74

Iria GONZALEZ-DOPESO-REYES

IR-Recherche

Phone : +33 (0)4 34 35 96 75

Room : 218

Caroline ISMEURT

Post-Doc

Phone : +33 (0)4 34 35 96 74

Room : 217

Thomas BUFFENOIR

IE-Recherche

Phone : +33 (0)4 34 35 96 74

Room : 217

Lucas ALONSO

Doctorant

Phone : +33 (0)4 34 35 96 59

Room : 219

Arianna BERTILACCIO

IE-Administratif

Phone : +33 (0)4 34 35 96 74

Room : 217

Lea VUIART

Doctorant

Phone : +33 (0)4 34 35 96 42

Room : RDC 04

Alexis CHAUSSY

AI-Recherche

Phone : +33 (0)4 34 35 96 74

Room : 217

Chloe VINCENT

Stagiaire

Phone : +33 (0)4 34 35 96 42

Room : RDC 04

Xavier PICHON

IR-Recherche

Phone : +33 (0)4 34 35 96 74

Room : 217

Maryse POLI

Stagiaire

Phone : +33 (0)4 34 35 96 74

Room : 217

Letizia CERUTTI

Doctorant

Phone : +33 (0)4 34 35 96 42

Room : 004

Alumni

Scientist

Vasiliki Kalatzis, Harry Wodrich, Sara Salinas

Assistant Professors

Franck Mennechet

PhD students

Matthieu Perreau, Nicolas Serratrice, Claire Hippert, Nadia Skander, Daniel Henaff, Sophie Creysells, Aurelie Cubizolle, Phuong Tran, Fabien Loustalot, Karsten Eichholz, Amani Wehbi, Océane Paris, Aline Raissa Ouoba

Post-docs

Olivier Billet, Karsten Eichholz, Charleine Zussy, Felix Junyent, Neus Bayo-Puxan, Thierry Bru, Khalil MAZOUNI, Hanna Dreja, Dominique Mercier, Anne Keriel, Kalpana Shrivastava, Hiep Tran, Danila del Rio, Coraline Chéneau, Phuong Tran, Océane Paris

Engineers

Aurelie Gennetier, Sandy Ibanes, Greg Conductier

Sélection de publications

Viral vector-mediated expression of NaV1.1, after seizure onset, reduces epilepsy in mice with Dravet syndrome

Saja Fadila 1 2 , Bertrand Beucher 3 4 , Iria González Dopeso-Reyes 3 , Anat Mavashov 5 , Marina Brusel 1 , Karen Anderson 1 , Caroline Ismeurt 3 , Ethan M Goldberg 6 7 , Ana Ricobaraza 8 , Ruben Hernandez-Alcoceba 8 , Eric J Kremer 3 , Moran Rubinstein 1 2 5

J Clin Invest . 2023 / pages 133(12):e159316

Inhibition of noradrenergic signalling in rodent orbitofrontal cortex impairs the updating of goal-directed actions

Juan Carlos Cerpa # 1 , Alessandro Piccin # 1 , Margot Dehove 1 , Marina Lavigne 2 , Eric J Kremer 2 , Mathieu Wolff 1 , Shauna L Parkes 1 , Etienne Coutureau 1

Elife 2023 / vol 12 / pages e81623

RNA transport from transcription to localized translation: a single molecule perspective

Eugenia Basyuk 1 2 , Florence Rage 3 , Edouard Bertrand 1 3 4

RNA Biol . 2021 / vol 18(9) / pages 1221-1237

Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins

Topaz Altman, Ariel Ionescu, Amjad Ibraheem, Dominik Priesmann, Tal Gradus-Pery, Luba Farberov, Gayster Alexandra, Natalia Shelestovich, Ruxandra Dafinca, Noam Shomron, Florence Rage, Kevin Talbot, Michael E. Ward, Amir Dori, Marcus Krüger & Eran Perlson

Nat Commun 2021 / vol 12(1) / pages 6914

Human innate lymphoid cell activation by adenoviruses is modified by host defense proteins and neutralizing antibodies

Océane Paris 1 , Franck J D Mennechet 1 , E J Kremer 1 Océane Paris 1 , Franck J D Mennechet 1 , E J Kremer 1

Front Immunol . 2022 / vol 13 / pages 975910

Splicing efficiency of minor introns in a mouse model of SMA predominantly depends on their branchpoint sequence and can involve the contribution of major spliceosome components

Valentin Jacquier 1 , Manon Prevot 1 , Thierry Gostan 1 , Remy Bordonne 1 , Sofia Benkhelifa-Ziyyat 2 , Martine Barkats 2 , Johann Soret 3

RNA 2021

Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA)

Pauline Duc 1 , Michel Vignes 2 , Gérald Hugon 3 , Audrey Sebban 4 , Gilles Carnac 3 , Eugene Malyshev 4 , Benoît Charlot 4 , Florence Rage 1

Lab Chip . 2021

Human innate lymphoid cell activation by adenoviruses is modified by host defence proteins and neutralizing antibodies

Paris O, Mennechet FDJ & EJ Kremer

Front Immunol. 2022 / pages In press

Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement

Karsten Eichholz # 1 , Tuan Hiep Tran # 1 , Coraline Chéneau # 1 , Thi Thu Phuong Tran 1 , Océane Paris 1 , Martine Pugniere 2 , Eric J Kremer 1

J Virol. 2022 / vol 96(6) / pages e0185021

Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens

Lynda Coughlan 1 , Eric J Kremer 2 , Dmitry M Shayakhmetov 3

Mol Ther. 2022 / vol 30(5) / pages 1822-1849

Adenovirus receptors on antigen-presenting cells of the skin

Elina Gerber-Tichet Dienst 1 , Eric J Kremer 1

Biol Cell. 2022 / pages Online ahead of print.

Editorial: Tropism, Mapping, Modeling, or Therapy Using Canine Adenovirus Type 2 (CAV-2) Vectors in the CNS

Iria Gonzalez Dopeso-Reyes 1 , Mathieu Wolff 2 , Melissa R Andrews 3 , Eric J Kremer 1

Front Mol Neurosci . 2021 / vol 14 / pages 636476

Lactoferrin Retargets Human Adenoviruses to TLR4 to Induce an Abortive NLRP3-Associated Pyroptotic Response in Human Phagocytes

Coraline Chéneau 1 , Karsten Eichholz 1 , Tuan Hiep Tran 1 , Thi Thu Phuong Tran 1 , Océane Paris 1 , Corinne Henriquet 2 , Jeffrey J Bajramovic 3 , Martine Pugniere 2 , Eric J Kremer 1

Front Immunol . 2021 / vol 12 / pages 685218

What is the risk of a deadly adenovirus pandemic?

Eric J Kremer 1

PLoS Pathog . 2021 / vol 17(9) / pages e1009814

IgG-Complexed Adenoviruses Induce Human Plasmacytoid Dendritic Cell Activation and Apoptosis

Thi Thu Phuong Tran 1 2 , Tuan Hiep Tran 1 3 4 , Eric J Kremer 1

Viruses 2021 / vol 13(9) / pages 1699

Thalamocortical and corticothalamic pathways differentially contribute to goal-directed behaviors in the rat.

Alcaraz F, Fresno V, Marchand AR, Kremer EJ, Coutureau E, Wolff M.

Elife 2018 / vol 7 / pages e32517

Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate.

Mestre-Francés N, Serratrice N, Gennetier A, Devau G, Cobo S, Trouche SG, Fontès P, Zussy C, De Deurwaerdere P, Salinas S, Mennechet FJ, Dusonchet J, Schneider BL, Saggio I, Kalatzis V, Luquin-Piudo MR, Verdier JM, Kremer EJ

JCI Insight. 2018 / vol 3(14) / pages pii: 98202

Humoral immune response to adenovirus induce tolerogenic bystander dendritic cells that promote generation of regulatory T cells.

Tran TTP, Eichholz K, Amelio P, Moyer C, Nemerow GR, Perreau M, Mennechet FJD, Kremer EJ

PLoS Pathog. 2018 / vol 14(8) / pages e1007127

Modular organization of the brainstem noradrenaline system coordinates opposing learning states

Uematsu A, Tan BZ, Ycu EA, Cuevas JS, Koivumaa J, Junyent F, Kremer EJ, Witten IB, Deisseroth K, Johansen JP.

Nature neurosci 2017 / vol 20(11) / pages 1602-1611

Splicing Defects of the Profilin Gene Alter Actin Dynamics in an S. pombe SMN Mutant.

Antoine M, Patrick KL, Soret J, Duc P, Rage F, Cacciottolo R, Nissen KE, Cauchi RJ, Krogan NJ, Guthrie C, Gachet Y, Bordonné R.

iScience 2019 / vol 23(1) / pages 100809

A new cis-acting motif is required for the axonal SMN-dependent Anxa2 mRNA localization

Rihan K, Antoine E, Maurin T, Bardoni B, Bordonné R, Soret J, Rage F.

RNA. 2017

CAV-2-Mediated GFP and LRRK2 G2019S Expression in the Macaca fascicularis Brain

Carla di Caudo, Ivan Martínez-Valbuena , Iñaki-Carril Mundiñano , Aurelie Gennetier , Maria Hernandez , Mar Carmona-Abellan , Irene Marcilla Garcia , Eric J Kremer , Rosario Luquin

Front Mol Neurosci 2020 / vol 13 / pages 49

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

Hayat H, Regev N, Matosevich N, Sales A, Paredes-Rodriguez E, Krom AJ, Bergman L, Li Y, Lavigne M, Kremer EJ,

Sci Adv 2020 / vol 6(15) / pages eaaz4232 eCollection 2020 Apr.

Targeted Transgene Expression in Cholinergic Interneurons in the Monkey Striatum Using Canine Adenovirus Serotype 2 Vectors

Martel AC, Elseedy H, Lavigne M, Scapula J, Ghestem A, Kremer EJ, Esclapez M, Apicella P.

Front Mol Neurosci. 2020 / vol 13:76 / pages eCollection 2020.

Location of the Cell Adhesion Molecule « Coxsackievirus and Adenovirus Receptor » in the Adult Mouse Brain

Wehbi A, Kremer EJ, Dopeso-Reyes IG.

Front Neuroanat . 2020 / vol 14:28 / pages eCollection 2020.

Targeting Catecholaminergic Systems in Transgenic Rats With a CAV-2 Vector Harboring a Cre-Dependent DREADD Cassette

Cerpa JC, Marchand AR, Salafranque Y, Pape JR, Kremer EJ, Coutureau E.

Front Mol Neurosci. 2020 / vol 13:121 / pages eCollection 2020

A review of 65 years of human adenovirus seroprevalence

Mennechet, F. J. D. Paris, O. Ouoba, A. R. Salazar Arenas, S. Sirima, S. B. Takoudjou Dzomo, G. R. Diarra, A. Traore, I. T. Kania, D. Eichholz, K. Weaver, E. A. Tuaillon, E. Kremer, E. J.

2019 / pages 1-17

Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson’s Disease

Lasbleiz C, Mestre-Francés N, Devau G, Luquin MR, Tenenbaum L, Kremer EJ, Verdier JM.

Front Mol Neurosci 2019 / vol 12 / pages 10

CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems

Del Rio D, Beucher B, Lavigne M, Wehbi A, Gonzalez Dopeso-Reyes I, Saggio I, Kremer EJ.

Front Mol Neurosci 2019 / vol 12 / pages 71

Combination of metformin with sodium selenite induces a functional phenotypic switch of human GM-CSF monocyte-derived macrophages.

Meziane W, Mekkaoui Z, Hai I, Kacimi K, Djilali K, Touil-Boukoffa C, Lefranc G, Fernandez A, Lamb N, Mennechet F, Aribi M.

Int Immunopharmacol. 2019 4 / vol 73 / pages 212-224

Thymoquinone Potently Enhances the Activities of Classically Activated Macrophages Pulsed with Necrotic Jurkat Cell Lysates and the Production of Antitumor Th1-/M1-Related Cytokines.

Miliani M, Nouar M, Paris O, Lefranc G, Mennechet F, Aribi M.

J Interferon Cytokine Res. 2018 / vol 38 (12)

Lysosomal and network alterations in human mucopolysaccharidosis type VII iPSC-derived neurons.

Bayó-Puxan N, Terrasso AP, Creyssels S, Simão D, Begon-Pescia C, Lavigne M, Salinas S, Bernex F, Bosch A, Kalatzis V, Levade T, Cuervo AM, Lory P, Consiglio A, Brito C, Kremer E.

Sci Rep 2018 / vol 8(1) / pages 16644

Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats

Hirschberg S, Li Y, Randall A, Kremer EJ, Pickering AE.

Elife. 2017

[Anti-adenovirus humoral immunity: impact on dendritic cell activation]

Mennechet FJD, Eichholz K, Tran TTP, Kremer EJ.

Med Sci (Paris). 2017

What is CAR doing in the middle of the adult neurogenic road?

Salinas S, Junyent F, Coré N, Cremer H, Kremer EJ.

Neurogenesis (Austin). 2017

[The coxsackievirus and adenovirus receptor is involved in cognitive processes]

Zussy C, Loustalot F, Junyent F, Kremer EJ, Salinas S.

Med Sci (Paris). 2017

Retrograde optogenetic characterization of the pontospinal module of the locus coeruleus with a canine adenoviral vector

Li, Y.; Hickey, L.; Perrins, R.; Werlen, E.; Patel, A. A.; Hirschberg, S.; Jones, M. W.; Salinas, S.; Kremer, E. J.; Pickering, A. E.

Brain Res 2016

Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity

Zussy, C.; Loustalot, F.; Junyent, F.; Gardoni, F.; Bories, C.; Valero, J.; Desarmenien, M. G.; Bernex, F.; Henaff, D.; Bayo-Puxan, N.; Chen, J. W.; Lonjon, N.; de Koninck, Y.; Malva, J. O.; Bergelson, J. M.; di Luca, M.; Schiavo, G.; Salinas, S.; Kremer, E. J.

J Neurosci 2016 / vol 36 / pages 9558-71

Membrane Dynamics and Signaling of the Coxsackievirus and Adenovirus Receptor

Loustalot, F.; Kremer, E. J.; Salinas, S.

Int Rev Cell Mol Biol 2016 / vol 322 / pages 331-62

Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells

Eichholz, K.; Bru, T.; Tran, T. T.; Fernandes, P.; Welles, H.; Mennechet, F. J.; Manel, N.; Alves, P.; Perreau, M.; Kremer, E. J.

PLoS Pathog 2016 / vol 12 / pages e1005871

[Is there a risk of zoonotic disease due to adenoviruses?]

Loustalot F, Creyssels S, Salinas S, Benkõ M, Harrach B, Mennechet FJ, Kremer EJ.

Med Sci (Paris). 2015

Impact of adenovirus life cycle progression on the generation of canine helper-dependent vectors

Fernandes, P.; Simao, D.; Guerreiro, M. R.; Kremer, E. J.; Coroadinha, A. S.; Alves, P. M.

Gene Ther 2015 / vol 22 / pages 40-9

Viral-genetic tracing of the input-output organization of a central noradrenaline circuit

Schwarz, L. A.; Miyamichi, K.; Gao, X. J.; Beier, K. T.; Weissbourd, B.; DeLoach, K. E.; Ren, J.; Ibanes, S.; Malenka, R. C.; Kremer, E. J.; Luo, L.

Nature 2015 / vol 524 / pages 88-92

Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model

Simao, D.; Pinto, C.; Fernandes, P.; Peddie, C. J.; Piersanti, S.; Collinson, L. M.; Salinas, S.; Saggio, I.; Schiavo, G.; Kremer, E. J.; Brito, C.; Alves, P. M.

Gene Ther 2015

Adenovirus tales: from the cell surface to the nuclear pore complex

Kremer, E. J.; Nemerow, G. R.

PLoS Pathog 2015 / vol 11 / pages e1004821

Canine helper-dependent vectors production: implications of Cre activity and co-infection on adenovirus propagation

Fernandes, P.; Almeida, A. I.; Kremer, E. J.; Alves, P. M.; Coroadinha, A. S.

Sci Rep 2015 / vol 5 / pages 9135

Ebola vaccines based on adenovirus vectors and risk of HIV

Kremer, E. J.; Van de Perre, P.

BMJ 2015 / vol 350 / pages h1307

Modeling human neural functionality in vitro: three-dimensional culture for dopaminergic differentiation

Simao, D.; Pinto, C.; Piersanti, S.; Weston, A.; Peddie, C. J.; Bastos, A. E.; Licursi, V.; Schwarz, S. C.; Collinson, L. M.; Salinas, S.; Serra, M.; Teixeira, A. P.; Saggio, I.; Lima, P. A.; Kremer, E. J.; Schiavo, G.; Brito, C.; Alves, P. M.

Tissue Eng Part A 2015 / vol 21 / pages 654-68

The intracellular domain of the coxsackievirus and adenovirus receptor differentially influences adenovirus entry

Loustalot, F.; Kremer, E. J.; Salinas, S.

J Virol 2015

Ebola virus vaccine: benefit and risks of adenovirus-based vectors

Mennechet, F. J.; Tran, T. T.; Eichholz, K.; van de Perre, P.; Kremer, E. J.

Expert Rev Vaccines 2015 / pages 1-8

Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups

Piersanti, S.; Burla, R.; Licursi, V.; Brito, C.; La Torre, M.; Alves, P. M.; Simao, D.; Mottini, C.; Salinas, S.; Negri, R.; Tagliafico, E.; Kremer, E. J.; Saggio, I.

PLoS One 2015 / vol 10 / pages e0133607

Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping

Beier, K. T.; Steinberg, E. E.; DeLoach, K. E.; Xie, S.; Miyamichi, K.; Schwarz, L.; Gao, X. J.; Kremer, E. J.; Malenka, R. C.; Luo, L.

Cell 2015 / vol 162 / pages 622-34

CAV-2-why a canine virus is a neurobiologist’s best friend

Junyent, F.; Kremer, E. J.

Curr Opin Pharmacol 2015 / vol 24 / pages 86-93

Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector

Serratrice, N.; Cubizolle, A.; Ibanes, S.; Mestre-Frances, N.; Bayo-Puxan, N.; Creyssels, S.; Gennetier, A.; Bernex, F.; Verdier, J. M.; Haskins, M. E.; Couderc, G.; Malecaze, F.; Kalatzis, V.; Kremer, E. J.

J Control Release 2014 / vol 181 / pages 22-31

Human coagulation factor X-adenovirus type 5 complexes poorly stimulate an innate immune response in human mononuclear phagocytes

Eichholz, K.; Mennechet, F.; Kremer, E. J.

J Virol 2014 / vol Dec 24

Do nonhuman primate or bat adenoviruses pose a risk for human health?

Benko, M.; Harrach, B.; Kremer, E. J.

Future Microbiol 2014 / vol 9 / pages 269-72

Central nervous system delivery of helper-dependent canine adenovirus corrects neuropathology and behavior in mucopolysaccharidosis type VII mice

Ariza, L.; Gimenez-Llort, L.; Cubizolle, A.; Pages, G.; Garcia-Lareu, B.; Serratrice, N.; Cots, D.; Thwaite, R.; Chillon, M.; Kremer, E. J.; Bosch, A.

Hum Gene Ther 2014 / vol 25 / pages 199-211

Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain

Cubizolle, A.; Serratrice, N.; Skander, N.; Colle, M. A.; Ibanes, S.; Gennetier, A.; Bayo-Puxan, N.; Mazouni, K.; Mennechet, F.; Joussemet, B.; Cherel, Y.; Lajat, Y.; Vite, C.; Bernex, F.; Kalatzis, V.; Haskins, M. E.; Kremer, E. J.

Mol Ther 2014 / vol 22 / pages 762-73

Nonhuman adenovirus vectors for gene transfer to the brain (BrainCAV).

[No authors listed]

Hum Gene Ther Clin Dev. 2014

Disruption of the coxsackievirus and adenovirus receptor- homodimeric interaction triggers lipid microdomain- and dynamin-dependent endocytosis and lysosomal targeting

Salinas, S.; Zussy, C.; Loustalot, F.; Henaff, D.; Menendez, G.; Morton, P. E.; Parsons, M.; Schiavo, G.; Kremer, E. J.

J Biol Chem 2013

Adenoviruses – from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting

Greber, U. F.; Arnberg, N.; Wadell, G.; Benko, M.; Kremer, E. J.

Cell Microbiol 2013 / vol 15 / pages 16-23

Impact of E1 and Cre on Adenovirus Vector Amplification: Developing MDCK CAV-2-E1 and E1-Cre Transcomplementing Cell Lines

Fernandes, P.; Santiago, V. M.; Rodrigues, A. F.; Tomas, H.; Kremer, E. J.; Alves, P. M.; Coroadinha, A. S.

PLoS One 2013 / vol 8 / pages e60342

Bioprocess development for canine adenovirus type 2 vectors

Fernandes, P.; Peixoto, C.; Santiago, V. M.; Kremer, E. J.; Coroadinha, A. S.; Alves, P. M.

Gene Ther 2013 / vol 20 / pages 353-60

Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats

Ord, E. N.; Shirley, R.; McClure, J. D.; McCabe, C.; Kremer, E. J.; Macrae, I. M.; Work, L. M.

J Cereb Blood Flow Metab 2013

Differentiated Neuroprogenitor Cells Incubated with Human or Canine Adenovirus, or Lentiviral Vectors Have Distinct Transcriptome Profiles

Piersanti, S.; Astrologo, L.; Licursi, V.; Costa, R.; Roncaglia, E.; Gennetier, A.; Ibanes, S.; Chillon, M.; Negri, R.; Tagliafico, E.; Kremer, E. J.; Saggio, I.

PLoS One 2013 / vol 8 (7) / pages e69808

Canine adenovirus type 2 vector generation via I-Sce1-mediated intracellular genome release

Ibanes, S.; Kremer, E. J.

PLoS One 2013 / vol 8 / pages e71032

A Siglec-like sialic-acid-binding motif revealed in an adenovirus capsid protein

Rademacher, C.; Bru, T.; McBride, R.; Robison, E.; Nycholat, C. M.; Kremer, E. J.; Paulson, J. C.

Glycobiology 2012 / vol 22 / pages 1086-91

The number of toll-like receptor 9-agonist motifs in the adenovirus genome correlates with induction of dendritic cell maturation by adenovirus immune complexes

Perreau, M.; Welles, H. C.; Pellaton, C.; Gjoksi, B.; Potin, L.; Martin, R.; Harari, A.; Bett, A.; Casimiro, D.; Gall, J.; Barouch, D. H.; Kremer, E. J.; Pantaleo, G.

J Virol 2012 / vol 86 / pages 6279-85

Virus induced and associated post-translational modifications

Salinas, S.; Kremer, E. J.

Biol Cell 2012 / vol 104 / pages 119-20

3D cultures of human neural progenitor cells: dopaminergic differentiation and genetic modification

Brito, C.; Simao, D.; Costa, I.; Malpique, R.; Pereira, C. I.; Fernandes, P.; Serra, M.; Schwarz, S. C.; Schwarz, J.; Kremer, E. J.; Alves, P. M.

Methods 2012 / vol 56 / pages 452-60

Helper-dependent canine adenovirus vector-mediated transgene expression in a neurodegenerative lysosomal storage disorder

Lau, A. A.; Rozaklis, T.; Ibanes, S.; Luck, A. J.; Beard, H.; Hassiotis, S.; Mazouni, K.; Hopwood, J. J.; Kremer, E. J.; Hemsley, K. M.

Gene 2012 / vol 491 / pages 53-7

Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants

Hippert, C.; Ibanes, S.; Serratrice, N.; Court, F.; Malecaze, F.; Kremer, E. J.; Kalatzis, V.

PLoS One 2012 / vol 7 / pages e35318

Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels

Bennasser, Y.; Chable-Bessia, C.; Triboulet, R.; Gibbings, D.; Gwizdek, C.; Dargemont, C.; Kremer, E. J.; Voinnet, O.; Benkirane, M.

Nat Struct Mol Biol 2011 / vol 18 / pages 323-7

DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa

Perreau, M.; Welles, H. C.; Harari, A.; Hall, O.; Martin, R.; Maillard, M.; Dorta, G.; Bart, P. A.; Kremer, E. J.; Tartaglia, J.; Wagner, R.; Esteban, M.; Levy, Y.; Pantaleo, G.

J Virol 2011 / vol 85 / pages 9854-62

An adenovirus traffic update: from receptor engagement to the nuclear pore

Henaff, D.; Salinas, S.; Kremer, E. J.

Future Microbiol 2011 / vol 6 / pages 179-92

SGSH gene transfer in mucopolysaccharidosis type IIIA mice using canine adenovirus vectors

Lau, A. A.; Hopwood, J. J.; Kremer, E. J.; Hemsley, K. M.

Mol Genet Metab 2010 / vol 100 / pages 168-75

An update on canine adenovirus type 2 and its vectors

Bru, T.; Salinas, S.; Kremer, E. J.

Viruses 2010 / vol 2 / pages 2134-53

A hitchhiker’s guide to the nervous system: the complex journey of viruses and toxins

Salinas, S.; Schiavo, G.; Kremer, E. J.

Nat Rev Microbiology 2010 / vol 8 / pages 645-55

A capsid-encoded PPxY-motif facilitates adenovirus entry

Wodrich, H.; Henaff, D.; Jammart, B.; Segura-Morales, C.; Seelmeir, S.; Coux, O.; Ruzsics, Z.; Wiethoff, C. M.; Kremer, E. J.

PLoS Pathog 2010 / vol 6 / pages e1000808

Mutagenesis of hexon « FX » hepatic tropism

Kremer, E. J.

Blood 2009 / vol 114 / pages 929-30

CAR-associated vesicular transport of an adenovirus in motor neuron axons

Salinas, S.; Bilsland, L. G.; Henaff, D.; Weston, A. E.; Keriel, A.; Schiavo, G.; Kremer, E. J.

PLoS Pathog 2009 / vol 5 / pages e1000442

Cystine accumulation in the CNS results in severe age-related memory deficits

Maurice, T.; Hippert, C.; Serratrice, N.; Dubois, G.; Jacquet, C.; Antignac, C.; Kremer, E. J.; Kalatzis, V.

Neurobiol Aging 2009 / vol 30 / pages 987-1000

The cell adhesion molecule « CAR » and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution

Seiradake, E.; Henaff, D.; Wodrich, H.; Billet, O.; Perreau, M.; Hippert, C.; Mennechet, F.; Schoehn, G.; Lortat-Jacob, H.; Dreja, H.; Ibanes, S.; Kalatzis, V.; Wang, J. P.; Finberg, R. W.; Cusack, S.; Kremer, E. J.

PLoS Pathog 2009 / vol 5 / pages e1000277

Gene transfer may be preventive but not curative for a lysosomal transport disorder

Hippert, C.; Dubois, G.; Morin, C.; Disson, O.; Ibanes, S.; Jacquet, C.; Schwendener, R.; Antignac, C.; Kremer, E. J.; Kalatzis, V.

Mol Ther 2008 / vol 16 / pages 1372-81

[Adenovirus hexon mediates liver gene transfer]

Henaff, D.; Kremer, E. J.

Med Sci (Paris) 2008 / vol 24 / pages 673-5

Three-dimensional structure of canine adenovirus serotype 2 capsid

Schoehn, G.; El Bakkouri, M.; Fabry, C. M. S.; Billet, O.; Estrozi, L. F.; Le, L.; Curiel, D. T.; Kajava, A. V.; Ruigrok, R. W. H.; Kremer, E. J.

J Virol 2008 / vol 82 / pages 3192-3203

Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

Perreau, M.; Pantaleo, G.; Kremer, E. J.

J Exp Med 2008 / vol 205 / pages 2717-25

The ocular anomalies in a cystinosis animal model mimic disease pathogenesis

Kalatzis, V.; Serratrice, N.; Hippert, C.; Payet, O.; Arndt, C.; Cazevieille, C.; Maurice, T.; Hamel, C.; Malecaze, F.; Antignac, C.; Muller, A.; Kremer, E. J.

Pediatr Res 2007 / vol 62 / pages 156-62

Interactions between human plasma components and a xenogenic adenovirus vector: reduced immunogenicity during gene transfer

Perreau, M.; Guerin, M. C.; Drouet, C.; Kremer, E. J.

Mol Ther 2007 / vol 15 / pages 1998-2007

Contrasting effects of human, canine, and hybrid adenovirus vectors on the phenotypical and functional maturation of human dendritic cells: implications for clinical efficacy

Perreau, M.; Mennechet, F.; Serratrice, N.; Glasgow, J. N.; Curiel, D. T.; Wodrich, H.; Kremer, E. J.

J Virol 2007 / vol 81 / pages 3272-84

Structural and mutational analysis of human Ad37 and canine adenovirus 2 fiber heads in complex with the D1 domain of coxsackie and adenovirus receptor

Seiradake, E.; Lortat-Jacob, H.; Billet, O.; Kremer, E. J.; Cusack, S.

Journal of Biological Chemistry 2006 / vol 281 / pages 33704-33716

The conundrum between immunological memory to adenovirus and their use as vectors in clinical gene therapy

Perreau, M.; Kremer, E. J.

Mol Biotechnol 2006 / vol 34 / pages 247-56

Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia

Hnasko, T. S.; Perez, F. A.; Scouras, A. D.; Stoll, E. A.; Gale, S. D.; Luquet, S.; Phillips, P. E. M.; Kremer, E. J.; Palmiter, R. D.

Proceedings of the National Academy of Sciences of the United States of America 2006 / vol 103 / pages 8858-8863

Canine adenovirus vectors for lung-directed gene transfer: efficacy, immune response, and duration of transgene expression using helper-dependent vectors

Keriel, A.; Rene, C.; Galer, C.; Zabner, J.; Kremer, E. J.

J Virol 2006 / vol 80 / pages 1487-96

Prevention of posterior capsule opacification by the induction of therapeutic apoptosis of residual lens cells

Malecaze, F.; Decha, A.; Serre, B.; Penary, M.; Duboue, M.; Berg, D.; Levade, T.; Lubsen, N. H.; Kremer, E. J.; Couderc, B.

Gene Therapy 2006 / vol 13 / pages 440-448

Lens cell targetting for gene therapy of prevention of posterior capsule opacification

Malecaze, F.; Lubsen, N. H.; Serre, B.; Decha, A.; Duboue, M.; Penary, M.; Berg, D.; Arnaud, J. D.; Titeux, M.; Kremer, E. J.; Couderc, B.

Gene Therapy 2006 / vol 13 / pages 1422-1429

Frequency, proliferation, and activation of human memory T cells induced by a nonhuman adenovirus

Perreau, M.; Kremer, E. J.

J Virol 2005 / vol 79 / pages 14595-605

Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding

Sotak, B. N.; Hnasko, T. S.; Robinson, S.; Kremer, E. J.; Palmiter, R. D.

Brain Research 2005 / vol 1061 / pages 88-96

Visualization of local Ca2+ dynamics with genetically encoded bioluminescent reporters

Rogers, K. L.; Stinnakre, J.; Agulhon, C.; Jublot, D.; Shorte, S. L.; Kremer, E. J.; Brulet, P.

European Journal of Neuroscience 2005 / vol 21 / pages 597-610

Gene transfer to the central nervous system: Current state of the art of the viral vectors

Kremer, E. J.

Current Genomics 2005 / vol 6 / pages 13-37

An adenovirus vector with a chimeric fiber derived from canine adenovirus type 2 displays novel tropism

Glasgow, J. N.; Kremer, E. J.; Hemminki, A.; Siegal, G. P.; Douglas, J. T.; Curiel, D. T.

Virology 2004 / vol 324 / pages 103-116

Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein

Disson, O.; Haouzi, D.; Desagher, S.; Loesch, K.; Hahne, M.; Kremer, E. J.; Jacquet, C.; Lemon, S. M.; Hibner, U.; Lerat, H.

Gastroenterology 2004 / vol 126 / pages 859-872

CAR chasing: canine adenovirus vectors-all bite and no bark?

Kremer, E. J.

J Gene Med 2004 / vol 6 Suppl 1 / pages S139-51

Long-term in vivo transduction of neurons throughout the rat CNS using novel helper-dependent CAV-2 vectors.

Soudais C, Skander N, Kremer EJ.

FASEB J. 2003

Widespread distribution of beta-hexosaminidase activity in the brain of a Sandhoff mouse model after coinjection of adenoviral vector and mannitol

Bourgoin, C.; Emiliani, C.; Kremer, E. J.; Gelot, A.; Tancini, B.; Gravel, R. A.; Drugan, C.; Orlacchio, A.; Poenaru, L.; Caillaud, C.

Gene Therapy 2003 / vol 10 / pages 1841-1849

A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model

Hemminki, A.; Kanerva, A.; Kremer, E. J.; Bauerschmitz, G. J.; Smith, B. F.; Liu, B.; Wang, M. H.; Desmond, R. A.; Keriel, A.; Barnett, B.; Baker, H. J.; Siegal, G. P.; Curiel, D. T.

Molecular Therapy 2003 / vol 7 / pages 163-173

Subpallial origin of a population of projecting pioneer neurons during corticogenesis

Morante-Oria, J.; Carleton, A.; Ortino, B.; Kremer, E. J.; Fairen, A.; Lledo, P. M.

Proceedings of the National Academy of Sciences of the United States of America 2003 / vol 100 / pages 12468-12473

[Canine adenovirus: useful for gene transfer in humans?]

Keriel A, Billet O, Kremer EJ.

Med Sci (Paris). 2003

Comparative transductions of breast cancer cells by three DNA viruses

Lucas, A.; Kremer, E. J.; Hemmi, S.; Luis, J.; Vignon, F. O.; Lazennec, G.

Biochemical and Biophysical Research Communications 2003 / vol 309 / pages 1011-1016

In vivo neuronal tracing with GFP-TTC gene delivery.

Kissa K, Mordelet E, Soudais C, Kremer EJ, Demeneix BA, Brûlet P, Coen L.

Mol Cell Neurosci. 2002

Muscle as a putative producer of acid alpha-glucosidase for glycogenosis type II gene therapy.

Martin-Touaux E, Puech JP, Château D, Emiliani C, Kremer EJ, Raben N, Tancini B, Orlacchio A, Kahn A, Poenaru L.

Hum Mol Genet. 2002

Trafficking and propagation of canine adenovirus vectors lacking a known integrin-interacting motif

Chillon, M.; Kremer, E. J.

Human Gene Therapy 2001 / vol 12 / pages 1815-1823

Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo

Soudais, C.; Laplace-Builhe, C.; Kissa, K.; Kremer, E. J.

Faseb Journal 2001 / vol 15 / pages 2283-+

Characterization of cis-acting sequences involved in canine adenovirus packaging

Soudais C, Boutin S, Kremer EJ.

Mol Ther. 2001

Canine adenovirus type 2 attachment and internalization: coxsackievirus-adenovirus receptor, alternative receptors, and an RGD-independent pathway

Soudais C, Boutin S, Hong SS, Chillon M, Danos O, Bergelson JM, Boulanger P, Kremer EJ.

J Virol. 2000

Canine adenovirus vectors: an alternative for adenovirus-mediated gene transfer

Kremer EJ, Boutin S, Chillon M, Danos O.

J Virol. 2000

Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a relevant model system for gene therapy of human prostatic cancer

Andrawiss M, Opolon P, Benihoud K, Devauchelle P, Di Falco N, Villette JM, Kremer E, Saulnier P, Berthon P, Perricaudet M, Cussenot O.

Prostate Cancer Prostatic Dis. 1999

Adenovirus-mediated transfer of the acid alpha-glucosidase gene into fibroblasts, myoblasts and myotubes from patients with glycogen storage disease type II leads to high level expression of enzyme and corrects glycogen accumulation

Nicolino MP, Puech JP, Kremer EJ, Reuser AJ, Mbebi C, Verdière-Sahuqué M, Kahn A, Poenaru L.

Human molecular genetics. 1998

A recombinant E1-deleted canine adenoviral vector capable of transduction and expression of a transgene in human-derived cells and in vivo

Klonjkowski B, Gilardi-Hebenstreit P, Hadchouel J, Randrianarison V, Boutin S, Yeh P, Perricaudet M, Kremer EJ.

Human gene therapy. 1997

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene

Tran PL, Weinbach J, Opolon P, Linares-Cruz G, Reynes JP, Grégoire A, Kremer E, Durand H, Perricaudet M.

The Journal of clinical investigation. 1997

Adenovirus vector-transduced hepatocytes implanted via a preformed collagen/PTFE support persist for at least 4 weeks in vivo

Kremer EJ, Di Falco ND, Opolon P, Perricaudet M.

Gene therapy 1996

Strategies for cancer gene therapy using adenoviral vectors

Descamps V, Duffour MT, Mathieu MC, Fernandez N, Cordier L, Abina MA, Kremer E, Perricaudet M, Haddada H.

Journal of molecular medicine (Berlin, Germany). 1996

Expression of the rat testis-specific histone H1t gene in transgenic mice. One kilobase of 5′-flanking sequence mediates correct expression of a lacZ fusion gene

Bartell JG, Davis T, Kremer EJ, Dewey MJ, Kistler WS.

The Journal of biological chemistry. 1996

Organoids direct systemic expression of erythropoietin in mice.

Descamps V, Blumenfeld N, Perricaudet M, Beuzard Y, Kremer EJ.

Gene Ther. 1995

Adenoviral vectors

Lee MG, Kremer EJ, Perricaudet M.

Molecular and cell biology of human diseases series. 1995

Adenovirus and adeno-associated virus mediated gene transfer

Kremer EJ, Perricaudet M.

British medical bulletin. 1995

Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis

Nancarrow JK, Kremer E, Holman K, Eyre H, Doggett NA, Le Paslier D, Callen DF, Sutherland GR, Richards RI.

Science (New York, N.Y.). 1994

A cytokine receptor gene cluster in the X-Y pseudoautosomal region?

Kremer E, Baker E, D'Andrea RJ, Slim R, Phillips H, Moretti PA, Lopez AF, Petit C, Vadas MA, Sutherland GR.

Blood. 1993

Evidence of founder chromosomes in fragile X syndrome.

Richards RI, Holman K, Friend K, Kremer E, Hillen D, Staples A, Brown WT, Goonewardena P, Tarleton J, Schwartz C.

Nature genetics. 1 1992

Fragile-X syndrome: unique genetics of the heritable unstable element

Yu S, Mulley J, Loesch D, Turner G, Donnelly A, Gedeon A, Hillen D, Kremer E, Lynch M, Pritchard M.

American journal of human genetics. 1992

The gene for the human IgA Fc receptor maps to 19q13.4.

Kremer EJ, Kalatzis V, Baker E, Callen DF, Sutherland GR, Maliszewski CR.

Human genetics. 1992

Analysis of the promoter for the gene encoding the testis-specific histone H1t in a somatic cell line: evidence for cell-cycle regulation and modulation by distant upstream sequences.

Kremer EJ, Kistler WS.

Gene. 1992

Prenatal diagnosis of fragile X syndrome by direct detection of the unstable DNA sequence.

Sutherland GR, Gedeon A, Kornman L, Donnelly A, Byard RW, Mulley JC, Kremer E, Lynch M, Pritchard M, Yu S.

The New England journal of medicine. 1991

Fragile X syndrome: genetic localisation by linkage mapping of two microsatellite repeats FRAXAC1 and FRAXAC2 which immediately flank the fragile site.

Richards RI, Holman K, Kozman H, Kremer E, Lynch M, Pritchard M, Yu S, Mulley J, Sutherland GR.

Journal of medical genetics. 1991

Localization of mRNA for testis-specific histone H1t by in situ hybridization.

Kremer EJ, Kistler WS.

Experimental cell research. 1991

Isolation of a human DNA sequence which spans the fragile X.

Kremer EJ, Yu S, Pritchard M, Nagaraja R, Heitz D, Lynch M, Baker E, Hyland VJ, Little RD, Wada M.

American journal of human genetics. 1991

Hereditary unstable DNA: a new explanation for some old genetic questions?

Sutherland GR, Haan EA, Kremer E, Lynch M, Pritchard M, Yu S, Richards RI.

Lancet (London, England). 1991

Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n

Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warren ST, Schlessinger D, Sutherland GR, Richards RI.

Science (New York, N.Y.). 1991

Fragile X genotype characterized by an unstable region of DNA

Yu S, Pritchard M, Kremer E, Lynch M, Nancarrow J, Baker E, Holman K, Mulley JC, Warren ST, Schlessinger D.

Science (New York, N.Y.). 1991

Isolation of a genomic clone encoding the rat histone variant, H1d.

Cole KD, Kandala JC, Kremer E, Kistler WS.

Gene. 1990

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Autres informations

Financement

EKL coordinates project iAds – “Intelligent design of adenovirus vectors”.

iAds is a European Innovation Council (EIC) Pathfinder project that aims to maximise the potential of adenovirus vector for vaccines and gene transfer.

The consortium of 6 partners from 5 European countries will dedicate 4 years to develop an intelligent design of adenovirus vectors (iAds). The project aims to maximise the potential of adenovirus vectors for vaccines and gene transfer. The objective is to revolutionise gene transfer and generate solutions in areas of unmet medical need via a platform that exploits the full potential of viral vectors. iAds aims to target specific cell types in the heart and brain to improve gene therapy efficacy and safety.

Gene therapy is a highly promising approach for treating certain diseases. Viral vectors have been developed stripped of their ability to cause disease and are instead used to deliver genetic material into cells for therapeutic purposes. Adenoviruses are particularly attractive because they can efficiently deliver DNA into both dividing and non-dividing cells. Funded by the European Innovation Council, the iAds project aims to overcome the limitations of adenoviral vectors, such as host immune responses and imperfect targeting. The consortium will create an in-silico platform for the design of intelligent adenovirus vectors with a focus on heart- and brain-specific targeting, addressing areas of unmet medical need.

For more information: www.intelligentadenoviruses.eu

Jobs / Internship

BOURSES DE MASTER INTERDISCIPLINAIRES IGMM

Voir l'annonce

Toutes les équipe de recherche

Mots-clés

Model organism studied

Nonhuman primates, dogs, rats, mice, primary human mononuclear phagocytes / Cellules humaines (motoneurones dérivés de cellulesIPS issues d’individus sains ou atteints de SMA)

Biological process

Immunology, intracellular trafficking, adult neurogenesis / Épissage, transport et traduction locale des ARN, activité synaptique de la jonction neuromusculaire.

Biological techniques

Cell biology, biochemistry, virology, immunology, gene transfer, gene therapy / Biologie moléculaire, culture cellulaire, jonction neuromusculaire 2D en chambre microfluidique.

Adénovirus : Récepteurs, Trafic Intracellulaire et Vectorologie

Eric J Kremer

Projets de recherche

Concours vidéo iAds pour les collégiens 2025

EKL coordinates project iAds – “Intelligent design of adenovirus vectors”

OUR PRINCIPLE AREAS OF INTEREST ARE:

1.Understanding the function of CAR, the coxsackievirus adenovirus receptor, in the healthy and disease brain, and during adenovirus trafficking.

2.Understanding how mononuclear phagocytes, in particular dendritic cells, process and respond to immune-complexed adenoviruses (IC-Ad)

3.Optimizing CAV-2 vector for gene transfer to the CNS

Le sous-groupe est composé de Florence Rage, Johann Soret, Pauline Duc et Audrey Moisan

Étude des mécanismes moléculaires de l’atrophie spinale (SMA)

Membres

Alumni

Scientist

Assistant Professors

PhD students

Post-docs

Engineers

Sélection de publications

Viral vector-mediated expression of NaV1.1, after seizure onset, reduces epilepsy in mice with Dravet syndrome

Inhibition of noradrenergic signalling in rodent orbitofrontal cortex impairs the updating of goal-directed actions

RNA transport from transcription to localized translation: a single molecule perspective

Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins

Human innate lymphoid cell activation by adenoviruses is modified by host defense proteins and neutralizing antibodies

Splicing efficiency of minor introns in a mouse model of SMA predominantly depends on their branchpoint sequence and can involve the contribution of major spliceosome components

Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA)

Human innate lymphoid cell activation by adenoviruses is modified by host defence proteins and neutralizing antibodies

Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement

Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens

Adenovirus receptors on antigen-presenting cells of the skin

Editorial: Tropism, Mapping, Modeling, or Therapy Using Canine Adenovirus Type 2 (CAV-2) Vectors in the CNS

Lactoferrin Retargets Human Adenoviruses to TLR4 to Induce an Abortive NLRP3-Associated Pyroptotic Response in Human Phagocytes

What is the risk of a deadly adenovirus pandemic?

IgG-Complexed Adenoviruses Induce Human Plasmacytoid Dendritic Cell Activation and Apoptosis

Thalamocortical and corticothalamic pathways differentially contribute to goal-directed behaviors in the rat.

Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate.

Humoral immune response to adenovirus induce tolerogenic bystander dendritic cells that promote generation of regulatory T cells.

Modular organization of the brainstem noradrenaline system coordinates opposing learning states

Splicing Defects of the Profilin Gene Alter Actin Dynamics in an S. pombe SMN Mutant.

A new cis-acting motif is required for the axonal SMN-dependent Anxa2 mRNA localization

CAV-2-Mediated GFP and LRRK2 G2019S Expression in the Macaca fascicularis Brain

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

Targeted Transgene Expression in Cholinergic Interneurons in the Monkey Striatum Using Canine Adenovirus Serotype 2 Vectors

Location of the Cell Adhesion Molecule « Coxsackievirus and Adenovirus Receptor » in the Adult Mouse Brain

Targeting Catecholaminergic Systems in Transgenic Rats With a CAV-2 Vector Harboring a Cre-Dependent DREADD Cassette

A review of 65 years of human adenovirus seroprevalence

Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson’s Disease

CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems

Combination of metformin with sodium selenite induces a functional phenotypic switch of human GM-CSF monocyte-derived macrophages.

Thymoquinone Potently Enhances the Activities of Classically Activated Macrophages Pulsed with Necrotic Jurkat Cell Lysates and the Production of Antitumor Th1-/M1-Related Cytokines.

Lysosomal and network alterations in human mucopolysaccharidosis type VII iPSC-derived neurons.

Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats

[Anti-adenovirus humoral immunity: impact on dendritic cell activation]

What is CAR doing in the middle of the adult neurogenic road?

[The coxsackievirus and adenovirus receptor is involved in cognitive processes]

Retrograde optogenetic characterization of the pontospinal module of the locus coeruleus with a canine adenoviral vector

Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity

Membrane Dynamics and Signaling of the Coxsackievirus and Adenovirus Receptor

Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells

[Is there a risk of zoonotic disease due to adenoviruses?]

Impact of adenovirus life cycle progression on the generation of canine helper-dependent vectors

Viral-genetic tracing of the input-output organization of a central noradrenaline circuit

Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model

Adenovirus tales: from the cell surface to the nuclear pore complex

Canine helper-dependent vectors production: implications of Cre activity and co-infection on adenovirus propagation

Ebola vaccines based on adenovirus vectors and risk of HIV

Modeling human neural functionality in vitro: three-dimensional culture for dopaminergic differentiation

The intracellular domain of the coxsackievirus and adenovirus receptor differentially influences adenovirus entry

Ebola virus vaccine: benefit and risks of adenovirus-based vectors

Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups

Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping

CAV-2-why a canine virus is a neurobiologist’s best friend

Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector

Human coagulation factor X-adenovirus type 5 complexes poorly stimulate an innate immune response in human mononuclear phagocytes

Do nonhuman primate or bat adenoviruses pose a risk for human health?

Central nervous system delivery of helper-dependent canine adenovirus corrects neuropathology and behavior in mucopolysaccharidosis type VII mice

Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain

Nonhuman adenovirus vectors for gene transfer to the brain (BrainCAV).

Disruption of the coxsackievirus and adenovirus receptor- homodimeric interaction triggers lipid microdomain- and dynamin-dependent endocytosis and lysosomal targeting

Adenoviruses – from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting