subject:(DDR1)

University of Toronto

1. Britto, Karen Elma. The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production.

Degree: 2010, University of Toronto

URL: http://hdl.handle.net/1807/25438

►

Atherosclerosis is an inflammatory disease of the cardiovascular system. Discoidin domain receptor 1 is a receptor tyrosine kinase that binds collagens. Previous work in our… (more)

Subjects/Keywords: DDR1; Macrophage; 0306

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Britto, K. E. (2010). The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/25438

Chicago Manual of Style (16^th Edition):

Britto, Karen Elma. “The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production.” 2010. Masters Thesis, University of Toronto. Accessed January 22, 2021. http://hdl.handle.net/1807/25438.

MLA Handbook (7^th Edition):

Britto, Karen Elma. “The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production.” 2010. Web. 22 Jan 2021.

Vancouver:

Britto KE. The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production. [Internet] [Masters thesis]. University of Toronto; 2010. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1807/25438.

Council of Science Editors:

Britto KE. The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production. [Masters Thesis]. University of Toronto; 2010. Available from: http://hdl.handle.net/1807/25438

Universitat Rovira i Virgili

2. Tomàs Roig, Jordi. Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals.

Degree: Departament de Medicina i Cirurgia, 2010, Universitat Rovira i Virgili

URL: http://hdl.handle.net/10803/8887

► We have demonstrated that myelin is deteriorated in schizophrenic patients. Discoidin domain 1 gene (DDR1) is expressed in myelin and it's also associated with schizophrenia.… (more)

▼ We have demonstrated that myelin is deteriorated in schizophrenic patients. Discoidin domain 1 gene (DDR1) is expressed in myelin and it's also associated with schizophrenia. Both findings were made by our research group. · Contributions and knowledge provided by the thesis In summary we can say that DDR1 is a key process of myelinazation. A down regulation of this gene might be associated with diseases of myelin. Study 1. It has been described a loss of myelin compaction and synthesis during the demyelination process. It has carried out an increase of compaction and synthesis of myelin during remielinization peak. 1. Structural alterations of mitochondria for the treatment of cuprizona. 2. Alterations in behavior. a. Period of exposure to cuprizone: less activity of the CNS, impairment function motor and less anxiety. b. Recovery period: increased activity of the CNS, impaired motor functions, less anxiety and less exploratory activity. 3. mRNA analysis have showed an increase of DDR1 expression during the remyelinization peak in parallel to another myelin gene. Study 2. From this study derived the following results: 1. Alterations in the area, the density of the axon and the thickness of the myelin sheath. 2. Decrease of the remyelinization potential. Alterations in behaviour: motor dysfunctions, hiporeactivity of the CNS, increase of anxiety and exploratory activity. Cuprizone accentuates the effects of anxious behaviour of these animals. Study 3.We described an increased expression of DDR1gene parallel to myelin genes. · Methodology used and most important conclusions This thesis focuses on two models to improve our knowledge of the role of DDR1 in myelinization. On one hand we have studied the expression of DDR1 in oligodendroglial cell lines undergoing differentiation. On the other hand has been characterized both histologically and functionally DDR1deficient mouse. The work was divided into three studies. Study 1. Behavioural features and ultrastructural myelin characterization during the second remyelinization period in those mice treated with cuprizone 0.2% for 6 weeks. It has been developed at the Faculty of Medicine and Health Sciences (Reus, Spain). Study 2. Behavioural characterization and myelin structure in knock-out mice for DDR1 and study its ability to carry out the remyelinization. It has been developed at the Faculty of Medicine and Health Sciences (Reus, Spain) and at the University of Toronto (Toronto, Canada). Descriptive study of DDR1 knock-out mice and their response to cuprizone treatment. Study 3. The discoidin domain receptor 1 is expressed during differentiation of the oligodendroglial cell line HOG16. It has been developed at the Faculty of Medicine and Health Sciences. In vitro study to evaluate changes in mRNA expression and changes in cells morphology. · Published papers: 1. Franco-Pons N, Tomàs J, Roig B, Auladell C, Martorell L, Vilella E. Discoidin domain… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Vilella Cuadrada, Elisabet (director).

Subjects/Keywords: DDR1 I MIELINA; 57; 576; 577; 616.8

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tomàs Roig, J. (2010). Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals. (Thesis). Universitat Rovira i Virgili. Retrieved from http://hdl.handle.net/10803/8887

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tomàs Roig, Jordi. “Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals.” 2010. Thesis, Universitat Rovira i Virgili. Accessed January 22, 2021. http://hdl.handle.net/10803/8887.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tomàs Roig, Jordi. “Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals.” 2010. Web. 22 Jan 2021.

Vancouver:

Tomàs Roig J. Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals. [Internet] [Thesis]. Universitat Rovira i Virgili; 2010. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10803/8887.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tomàs Roig J. Contribució del receptor domini discoidina 1 (ddr1) en el procés de mielinització. Aplicació de diferents models experimentals. [Thesis]. Universitat Rovira i Virgili; 2010. Available from: http://hdl.handle.net/10803/8887

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Tosti, Priscillia. Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1.

Degree: Docteur es, Biochimie et Biologie Moléculaire, 2014, Université Montpellier I

URL: http://www.theses.fr/2014MON1T007

►

Le cancer colorectal (CCR) demeure l'une des principales causes de décès par cancer dans le monde. Récemment, une nouvelle immunothérapie basée sur le ciblage du… (more)

▼

Le cancer colorectal (CCR) demeure l'une des principales causes de décès par cancer dans le monde. Récemment, une nouvelle immunothérapie basée sur le ciblage du récepteur à activité tyrosine kinase (RTK) EGFR via l'anticorps cetuximab a montré une amélioration significative de la survie des patients atteints de CCR métastatique (CCRm). Cependant, une grande partie de ces patients présente une résistance qui est associée à la présence de mutations gains de fonction dans la voie de signalisation Ras. Dans ce contexte, l'identification de cibles thérapeutiques Ras-indépendantes pourrait avoir un intérêt particulier. Une analyse pharmacologique effectuée au laboratoire démontre que le nilotinib, un inhibiteur de la TK oncogénique BCR-ABL utilisée en clinique pour le traitement des leucémies myéloïdes chroniques, affecte également les propriétés invasives et métastatiques de cellules de CCR. Nous avons identifié la cible majoritaire de cet inhibiteur dans cette réponse tumorale : il s'agit de DDR1, un récepteur au collagène ayant une activité TK intrinsèque. Mon travail de thèse a mis en évidence que DDR1 est fréquemment et fortement activé dans les métastases de patients atteints de CCR. J'ai ensuite analysé la signalisation DDR1-dépendante dans ces cellules tumorales par phosphoprotéomique quantitative. Cette analyse montre la nature Ras-indépendante de cette signalisation et révèle la protéine de signalisation BCR comme un nouveau substrat essentiel de DDR1 pour induire l'invasion cellulaire. Enfin, je montre que l'inhibition de DDR1 par le nilotinib améliore la réponse au cetuximab y compris pour les cellules tumorales ayant une mutation oncogénique de K-Ras ou B-Raf. En conclusion, ces résultats suggèrent que le ciblage de DDR1 par le nilotinib pourrait avoir un intérêt thérapeutique dans le traitement des CCRm.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the Western world. Cancer that metastasizes to distant sites is usually not curable, although chemotherapy can extend survival. Recently, a novel immunotherapy approach based on targeting the EGFR tyrosine kinase (TK) via the antibody cetuximab was shown to significantly improve the survival of patients with metastatic CRC (mCRC). However, only patients with wild-type KRAS may hope to gain from EGFR inhibition. The majority of patients expresses oncogenic K-Ras alleles and thus have hyperactive Ras cascade operating independently from EGFR. Therefore, there is an urgent need for discovery of a new Ras-independent target that regulates tumor cell invasion and metastasis in mCRC. A pharmacological approach in the lab revealed that the small inhibitor of the leukemic TK BCR-Abl also inhibits invasive and metastatic abilities of CRC cells. This effect was also observed in cells expressing deregulated KRAS signalling. We next identified the receptor for collagen and atypical TK DDR1 as that the main target of nilotinib in these cells. Accordingly, DDR1 was found frequently and strongly activated in metastatic nodules of CRC…

Advisors/Committee Members: Roche, Serge (thesis director).

Subjects/Keywords: Cancer colorectal; Recepteur DDR1; Metastase; Collagène; Colorectal cancer; Collagen receptor DDR1; Metastases

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tosti, P. (2014). Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2014MON1T007

Chicago Manual of Style (16^th Edition):

Tosti, Priscillia. “Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1.” 2014. Doctoral Dissertation, Université Montpellier I. Accessed January 22, 2021. http://www.theses.fr/2014MON1T007.

MLA Handbook (7^th Edition):

Tosti, Priscillia. “Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1.” 2014. Web. 22 Jan 2021.

Vancouver:

Tosti P. Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1. [Internet] [Doctoral dissertation]. Université Montpellier I; 2014. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2014MON1T007.

Council of Science Editors:

Tosti P. Le Nilotinib inhibe les propriétés invasives et métastasantes des cellules de cancer colorectal en ciblant le récepteur à activité tyrosine kinase DDR1 : The anti-leukemic drug nilotinib inhibits invasive and metastatic properties of colorectal cancer cells by targeting the collagen receptor DDR1. [Doctoral Dissertation]. Université Montpellier I; 2014. Available from: http://www.theses.fr/2014MON1T007

4. Berestjuk, Ilona. Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies.

Degree: Docteur es, Sciences de la vie et de la santé, 2019, Université Côte d'Azur (ComUE)

URL: http://www.theses.fr/2019AZUR6029

► Le mélanome est un cancer de la peau très agressif de part son fort potentiel métastatique et sa résistance aux traitements. La progression tumorale est… (more)

▼ Le mélanome est un cancer de la peau très agressif de part son fort potentiel métastatique et sa résistance aux traitements. La progression tumorale est accompagnée par des mutations « drivers » qui touchent principalement les gènes BRAF et NRAS et conduisent à l’activation constitutive de la voie des MAP kinases. De nouvelles options thérapeutiques comme les thérapies ciblées associant un inhibiteur de BRAF (vémurafénib) et un inhibiteur de MEK (tramétinib), et les immunothérapies sont indiquées mais ces traitements ne bénéficient qu'à certains patients et leur utilisation est limitée du fait de l'émergence de résistances primaires et secondaires. Il est donc fondamental de mieux comprendre les mécanismes de l'échappement aux thérapies ciblées dans le but d'en améliorer l'efficacité.La capacité des cellules cancéreuses à résister aux traitements repose en partie sur leur pouvoir d’adaptation au microenvironnement tumoral. Au sein d’une tumeur, la cellule cancéreuse interagit avec un écosystème complexe composé de cellules stromales dont des fibroblastes activés et de la matrice extracellulaire (MEC). La MEC, majoritairement produite par les fibroblastes est composée de molécules d’adhérence comme la fibronectine et de structure comme les collagènes. Elle constitue un réseau dynamique ayant des propriétés biochimiques et mécaniques qui influencent la progression tumorale. Ainsi, le stroma dans lequel sont ancrées les mélanomes et les interactions qu’ils entretiennent avec la MEC peuvent avoir un rôle prépondérant dans la résistance aux thérapies ciblées. Cette résistance induite par l’adhérence des cellules à une matrice est définie comme la MM-DR (Matrix Mediated-Drug Resistance).Dans un premier temps mes études ont montrés, a l’aide d’un modèle 3D de MEC, que les FRCs (Fibroblasts Reticular Cells) ou différentes populations de MAFs (Melanoma Associated Fibroblasts) isolées de biopsies de métastases lymphatiques produisent et remodèlent une MEC riche en fibres de collagènes, d’enzymes d’échafaudage et de protéines matricielles qui est plus rigide qu’une MEC produite par des fibroblastes d’origine dermique. J’ai également observé un effet « protecteur » de ces matrices sur les mélanomes face aux thérapies. L’adhérence des cellules de mélanome conduit à une résistance en réponse aux effets anti-prolifératifs des inhibiteurs de BRAF et de MEK. Dans un deuxième temps j’ai identifiée les DDRs (Discoidin Domain Receptors 1 & 2), deux récepteurs de collagène à l’activité tyrosine kinase et qui fonctionnent indépendamment des intégrines, comme étant impliqués dans la MM-DR. Par une approche d’interférence ARN et par une approche pharmacologique, j’ai montré que l’inhibition de DDR1 et de DDR2 ré-sensibilise les cellules cultivées sur matrice aux effets cytostatiques et cytotoxiques du vémurafénib. Ces résultats ont étaient également confirmés par une approche in vivo en utilisant un modèle de xénogreffe. En effet, le traitement des souris avec la combinaison Vémurafénib + Imatinib (un inhibiteur de tyrosine kinase utilisé… Advisors/Committee Members: Tartare-Deckert, Sophie (thesis director).

Subjects/Keywords: Mélanome; Fibroblastes; Matrice extracellulaire; DDR1; DDR2; Thérapies ciblées; Melanoma; Fibroblasts; Extracellular matrix; DDR1; DDR2; Targeted therapies

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Berestjuk, I. (2019). Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies. (Doctoral Dissertation). Université Côte d'Azur (ComUE). Retrieved from http://www.theses.fr/2019AZUR6029

Chicago Manual of Style (16^th Edition):

Berestjuk, Ilona. “Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies.” 2019. Doctoral Dissertation, Université Côte d'Azur (ComUE). Accessed January 22, 2021. http://www.theses.fr/2019AZUR6029.

MLA Handbook (7^th Edition):

Berestjuk, Ilona. “Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies.” 2019. Web. 22 Jan 2021.

Vancouver:

Berestjuk I. Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies. [Internet] [Doctoral dissertation]. Université Côte d'Azur (ComUE); 2019. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2019AZUR6029.

Council of Science Editors:

Berestjuk I. Rôle de la matrice extracellulaire et des récepteurs à domaine discoïdine, DDR1 et DDR2, dans la résistance des cellules de mélanome aux thérapies ciblées : Role of extracellular matrix and discoidin domain receptors, DDR1 and DDR2, in the resistance of melanoma cells to targeted therapies. [Doctoral Dissertation]. Université Côte d'Azur (ComUE); 2019. Available from: http://www.theses.fr/2019AZUR6029

5. Di Martino, Julie. Actine : entre structure et mouvement : Actin : between structure and movement.

Degree: Docteur es, Biologie cellulaire et physiopathologie, 2015, Bordeaux

URL: http://www.theses.fr/2015BORD0269

►

L’actine est impliquée dans de nombreuses fonctions cellulaires physiologiques et pathologiques. Au cours de ma thèse j'ai analysé le rôle de l'actine i) lors de… (more)

▼

L’actine est impliquée dans de nombreuses fonctions cellulaires physiologiques et pathologiques. Au cours de ma thèse j'ai analysé le rôle de l'actine i) lors de l’invasion tumorale et ii) dans la formation des fenêtres des cellules endothéliales sinusoïdales hépatiques. i) Les cellules tumorales forment des structures d’actine permettant la dégradation de la matrice extracellulaire (MEC) nommés invadosomes. Mes travaux ont permis de démontrer que la RhoGTPase Cdc42 régule la formation de la structure d’actine qu’est l’invadosome, tandis que la protéine d’échafaudage Tks5 est requise pour l’activité de dégradation aboutissant à un invadosome fonctionnel. Ces deux molécules constituent la signature moléculaire minimale des invadosomes. Nous avons établi que le collagène de type I qui est surexprimé dans le microenvironnement tumoral induit la formation d’invadosomes linéaires (Lis). Nous avons identifié le récepteur à domaine discoïdine 1 (DDR1) comme spécifiquement responsable de la formation des Lis. Son interaction avec le collagène fibrillaire permet le recrutement du facteur d’échange des RhoGTPases, Tuba et l’activation de la Cdc42 conduisant à la formation d’un Li. DDR1 est impliqué dans l’invasion tumorale et sa surexpression est de mauvais pronostic dans plusieurs cancers comme le poumon ou encore le sein. Le récepteur DDR1 est également impliqué dans la cohésion cellulaire au cours de la migration collective des cellules tumorales. Nous avons démontré que dans un contexte riche en collagène de type I, DDR1 a une double localisation et donc différents rôles associés dans la migration collective. D’une part un rôle de cohésion cellulaire et d’autre part un rôle dans la dégradation de la MEC. Nous tentons de démontrer que ces différentes fonctions impliquent différentes isoformes de DDR1. Nous souhaitons par la suite déterminer les mécanismes moléculaires qui régulent l’expression, la localisation et la signalisation associées aux différentes isoformes de DDR1. ii) Dans un contexte physiologique, les capillaires sanguins du foie présentent des pores transcellulaires ou fenêtres, qui permettent les échanges bidirectionnels entre le sang et les hépatocytes pour assurer la fonction de filtration de cet organe. Au cours du processus de fibrose ces fenêtres sont perdues, réduisant les échanges. Nous avons démontré le caractère réversible de la perte des fenêtres mais aussi que l’actine n’était pas impliquée dans la formation de ces structures. Nous avons développé une méthode de visualisation en microscopie haute résolution STED de ces structures, permettant pour la première fois une analyse sur cellule vivante. Par une approche de spectrométrie de masse couplée à notre nouvelle méthode d’observation en STED, nous voulons valider la co-localisation des fenêtres avec des marqueurs potentiels identifiés.

Actin is involved in many physiological and pathological cellular functions. In my thesis I analyzed the role of actin i) during tumor invasion and ii) in the formation of fenestrae in liver sinusoidal endothelial…

Advisors/Committee Members: Saltel, Frédéric (thesis director).

Subjects/Keywords: Actine; Invadosome; Foie; Invasion; Migration; DDR1; Fibrose; Cellules endothéliales; Fenêtres; Actin; Invadosome; Liver fibrosis; Endothelial cells; Invasion; Migration; DDR1; Fenestrae

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Di Martino, J. (2015). Actine : entre structure et mouvement : Actin : between structure and movement. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2015BORD0269

Chicago Manual of Style (16^th Edition):

Di Martino, Julie. “Actine : entre structure et mouvement : Actin : between structure and movement.” 2015. Doctoral Dissertation, Bordeaux. Accessed January 22, 2021. http://www.theses.fr/2015BORD0269.

MLA Handbook (7^th Edition):

Di Martino, Julie. “Actine : entre structure et mouvement : Actin : between structure and movement.” 2015. Web. 22 Jan 2021.

Vancouver:

Di Martino J. Actine : entre structure et mouvement : Actin : between structure and movement. [Internet] [Doctoral dissertation]. Bordeaux; 2015. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2015BORD0269.

Council of Science Editors:

Di Martino J. Actine : entre structure et mouvement : Actin : between structure and movement. [Doctoral Dissertation]. Bordeaux; 2015. Available from: http://www.theses.fr/2015BORD0269

6. Henriet, Elodie. Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation.

Degree: Docteur es, Biologie cellulaire et physiopathologie, 2017, Bordeaux

URL: http://www.theses.fr/2017BORD0797

►

Les invadosomes sont des structures d’invasion plastiques et dynamiques qui interagissent avec leur microenvironnement. Ils possèdent différentes fonctions telles que l’adhésion, la mécanotransduction ou encore… (more)

▼

Les invadosomes sont des structures d’invasion plastiques et dynamiques qui interagissent avec leur microenvironnement. Ils possèdent différentes fonctions telles que l’adhésion, la mécanotransduction ou encore la dégradation de la matrice extracellulaire (MEC). Mon travail de thèse s’est concentré sur i) l’étude globale de la composition des invadosomes par spectrométrie de masse et ii) sur l’impact d’éléments du microenvironnement dans la formation de ces structures d’invasion.i) Les invadosomes sont des complexes multi-protéiques dont tous les partenaires ne sont pas encore totalement identifiés. Au laboratoire, une nouvelle approche combinant la microdissection laser suivie d’une analyse par spectrométrie de masse, a été développée. Cette technique a été appliquée à l’étude des invadosomes rosettes. Nous avons ainsi mis en évidence une nouvelle fonction associée aux invadosomes, en les définissants comme des sites actifs de traduction protéique. Les invadosomes cependant, sont des structures plastiques dont la formation et la morphologie sont modulées par différents éléments de l’environnement. Nous souhaitons à présent déterminer les partenaires communs et spécifiques entre les différentes organisations des invadosomes afin d’identifier les molécules impliquées dans cette plasticité.ii) La formation des invadosomes peut être induite par différents éléments du microenvironnement comme des facteurs de croissance ou encore la composition et la rigidité de la MEC. Le TGF-β est un facteur de croissance impliqué dans la formation des invadosomes, dans la promotion de la rigidité de la MEC et dans la fibrose hépatique pouvant mener au développement du carcinome hépatocellulaire. Nous avons alors étudié l’impact du TGF-β dans la formation des invadosomes linéaires en contexte de collagène de type I. Nous montrons que le TGF-β module la machinerie moléculaire associée aux invadosomes linéaires en induisant l’expression de DDR1 et MT1-MMP, ainsi que des éléments impliqués dans leur formation tels que le collagène I. Ces modulations sont dépendantes de la voie de signalisation canonique du TGF-β passant par Smad4 et favorisent la formation et l’activité des invadosomes linéaires. De plus, le TGF-β induit une surexpression de la LOXL2 qui est une enzyme de réticulation du collagène, augmentant la rigidité de la matrice ce qui favorise la formation des invadosomes.Les résultats obtenus durant ma thèse auront permis de mieux définir les éléments impliqués dans la composition et la formation des invadosomes.

Invadosomes are plastic and dynamic invasive structures interacting with the microenvironement. Those structures are involved in several functions as adhesion, mecanotransduction and degradation of the extracellular matrix (ECM). My PhD work focuses on i) the study of the invadosomes composition by mass spectrometry and ii) on the impact of microenvironmental elements on the formation of those invasive structures.i) Invadosomes are multi-protein complexes in which all partners are not yet fully identified. In the…

Advisors/Committee Members: Saltel, Frédéric (thesis director).

Subjects/Keywords: Invadosomes; Traduction; Plasticité; DDR1; TGF-β; Collagène de type I; Invadosomes; Translation; Plasticity; DDR1; TGF-β; Type I collagen

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Henriet, E. (2017). Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2017BORD0797

Chicago Manual of Style (16^th Edition):

Henriet, Elodie. “Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation.” 2017. Doctoral Dissertation, Bordeaux. Accessed January 22, 2021. http://www.theses.fr/2017BORD0797.

MLA Handbook (7^th Edition):

Henriet, Elodie. “Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation.” 2017. Web. 22 Jan 2021.

Vancouver:

Henriet E. Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation. [Internet] [Doctoral dissertation]. Bordeaux; 2017. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2017BORD0797.

Council of Science Editors:

Henriet E. Impact du microenvironnement dans la composition, la plasticité et la formation des invadosomes : Microenvironment involvement in invadosomes composition, plasticity and formation. [Doctoral Dissertation]. Bordeaux; 2017. Available from: http://www.theses.fr/2017BORD0797

Universitat Rovira i Virgili

7. Roig Bourgine, Bàrbara. Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia.

Degree: Departament de Medicina i Cirurgia, 2007, Universitat Rovira i Virgili

URL: http://hdl.handle.net/10803/8860

► Schizophrenia is one of the most common psychoses in the world today. It has a prevalence of 1% in the population and is of unknown… (more)

▼ Schizophrenia is one of the most common psychoses in the world today. It has a prevalence of 1% in the population and is of unknown etiology. One of the most widely accepted etiopathogenic hypotheses for schizophrenia is neurodevelopmental theory, which postulates that schizophrenia originates from a variety of neurogenetic and gliogenetic disorders during perinatal development. Many studies have reported that schizophrenic patients have alterations in their myelin (white matter of the brain). Axons must be myelinated if signals are to be properly transmitted between neurons. The cells that form the myelin sheaths of the axons in the CNS are the oligodendrocytes. In humans, the myelination process peaks in the perinatal, childhood and adolescence stages. It is during this last stage that the symptoms of schizophrenia become manifest. Several linkage studies indicate that the 6p chromosomal region may contain one or more susceptibility genes for schizophrenia. Our group chose a gene in this region, the gene encoding the discoidin domain receptor 1 (DDR1), as a candidate gene for schizophrenia. DDR1 is known to be a receptor tyrosine kinase which is highly expressed in proliferative areas during murine brain development, and has also been shown to be expressed in human brain. The DDR1 ligand is collagen, which promotes the proliferation and differentiation of the neurophitelial cells in rats. Our group has observed that DDR1 is significantly expressed in the white matter and particularly in oligodendrocytes during pre- and postnatal development in mice. Furthermore, the expression of this receptor follows a spatial-temporal pattern similar to the process of myelination. In this doctoral thesis we have made the first detailed study of the pattern of gene and protein expression of DDR1 in human brain, using specific techniques such as in situ hybridization, immunohistochemistry and quantification of RNAm. We found a positive association of DDR1 with schizophrenia in a case-control association study using markers of the SNP (single nucleotide polymorphism) type. We have also reported for the first time that DDR1 is a myelin protein in the human brain and that of the five different isoforms that are known only isoforms DDR1c and DDR1a are related to the myelin. The following scientific articles have been written as a result of this doctoral thesis: - Roig B, Virgos C, Franco N, Martorell L, Valero J, Costas J, Carracedo A, Labad A, Vilella E. The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. Molecular Psychiatry. 2007. doi: 10.1038/sj.mp.4001995. IF: 11.8 - Roig B, Franco-Pons N, Martorell L, Tomàs J, Costas J, Vogel WF, Vilella E. Identification of the tyrosine kinase receptor discoidin domain 1 (DDR1) as a novel myelin protein. Submitted to Glia. IF: 4.1 - Roig B, Franco-Pons N, Martorell L, Vilella E. Quantitative analysis of DDR1 mRNA expression in normal and schizophrenic brain. Manuscript in preparation. Advisors/Committee Members: [email protected] (authoremail), false (authoremailshow), Vilella Cuadrada, Elisabet (director).

Subjects/Keywords: mielina; esquizofrènia; DDR1; 575; 576

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roig Bourgine, B. (2007). Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia. (Thesis). Universitat Rovira i Virgili. Retrieved from http://hdl.handle.net/10803/8860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Roig Bourgine, Bàrbara. “Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia.” 2007. Thesis, Universitat Rovira i Virgili. Accessed January 22, 2021. http://hdl.handle.net/10803/8860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Roig Bourgine, Bàrbara. “Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia.” 2007. Web. 22 Jan 2021.

Vancouver:

Roig Bourgine B. Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia. [Internet] [Thesis]. Universitat Rovira i Virgili; 2007. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10803/8860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Roig Bourgine B. Expressió del receptor domini discoidina 1 (DDR1) en cervell huma. Relació amb l'esquizofrènia. [Thesis]. Universitat Rovira i Virgili; 2007. Available from: http://hdl.handle.net/10803/8860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Michigan

8. Ruggeri, Jeanine. Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma.

Degree: PhD, Molecular and Integrative Physiology, 2020, University of Michigan

URL: http://hdl.handle.net/2027.42/162978

► Pancreatic ductal adenocarcinoma (PDA) is an aggressive and devastating malignancy characterized by a collagen-rich, fibroinflammatory stroma. In the presence of a persistent injury as seen… (more)

▼ Pancreatic ductal adenocarcinoma (PDA) is an aggressive and devastating malignancy characterized by a collagen-rich, fibroinflammatory stroma. In the presence of a persistent injury as seen in chronic pancreatitis, a risk factor for the development of PDA, or oncogenic KRAS, the pancreas undergoes an initial morphological event where healthy acinar cells transdifferentiate into a ductal-like phenotype in a process called acinar-ductal metaplasia (ADM). ADM can advance into pre-cancerous lesions with a concomitant increase in collagen deposition. Due to the lack of clinical symptoms, limitations in early diagnosis and the excess collagen production that creates a barrier for treatment options, most patients are diagnosed with metastatic PDA leaving them with a 10% 5-year survival rate. Therefore, understanding the initiating molecular events of PDA and the crosstalk between the collagen-dense ECM and tumor cells is essential in providing early diagnostic methods with the potential for treatment options of this deadly disease. To understand the molecular interactions between tumor-derived epithelial cells and the collagen dense stroma, this project focuses on a set of receptor tyrosine kinases called Discoidin Domain Receptors, DDR1 and DDR2, that bind to fibrillar collagens. This facilitates cell proliferation, migration, adhesion, and extracellular matrix remodeling. DDR1 has been shown to be expressed in epithelial cells, while DDR2 is found in the mesenchymal compartment such as fibroblasts and connective tissue. The aim of this project was to define the roles of DDRs, independently of each other, in the pathogenesis of pancreatic disease where overproduction of collagen can serve as a natural reservoir for DDR activation. To determine the significance of DDR1 in a model of experimental pancreatitis, I utilized a DDR1-ablated mouse (DDR1-/-). DDR1-/- mice were subjected to cerulein, a cholecystokinin ortholog that induces acinar cell stress to mimic the events of ADM and increased fibrosis seen in human pancreatitis. DDR1-/- mice were also crossed into the established KrasG12D/+; Ptf1aCre/+ (KC) model of tumorigenesis and the KrasLSL-G12D/+; Trp53LSL-R172H/+; Ptf1aCre/+ (KPC) of metastasis. A common phenotype observed among all models in the absence of DDR1 was significant tissue atrophy, acinar cell dropout, and perturbation in proliferation, suggesting DDR1 is necessary for pancreatic tissue homeostasis and recovery following extended injury. To study the role of DDR2 in PDA development, we used a conditional DDR2 knockout mouse (DDR2fl/fl) and bred them into the KC and KPC model. However, this only allows for DDR2 depletion within the pancreatic epithelium. To address the role of DDR2 in both the epithelial and mesenchymal compartments, we crossed DDR2fl/fl into the dual recombinase system using global B-actinCreERT2 to knockout DDR2 and the KrasFSF-G12D/+; Ptf1aFlpo/+ (KF) to induce tumorigenesis and KrasFSF-G12D/+; Trp53+/- Ptf1aFlpo/+ (KPF) for studies in stages, including metastases. The… Advisors/Committee Members: Crawford, Howard C (committee member), Moore, Bethany B (committee member), Lyssiotis, Costas Andreas (committee member), Shah, Yatrik M (committee member).

Subjects/Keywords: DDR1 and Pancreatic Ductal Adenocarcinoma; Molecular, Cellular and Developmental Biology; Science

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ruggeri, J. (2020). Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/162978

Chicago Manual of Style (16^th Edition):

Ruggeri, Jeanine. “Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma.” 2020. Doctoral Dissertation, University of Michigan. Accessed January 22, 2021. http://hdl.handle.net/2027.42/162978.

MLA Handbook (7^th Edition):

Ruggeri, Jeanine. “Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma.” 2020. Web. 22 Jan 2021.

Vancouver:

Ruggeri J. Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma. [Internet] [Doctoral dissertation]. University of Michigan; 2020. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2027.42/162978.

Council of Science Editors:

Ruggeri J. Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma. [Doctoral Dissertation]. University of Michigan; 2020. Available from: http://hdl.handle.net/2027.42/162978

9. Dorison, Aude. Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases.

Degree: Docteur es, Physiologie et Physiopathologie Rénales, 2016, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2016PA066144

►

Les maladies rénales ont un impact socio-économique majeur sur la santé publique nécessitant le développement de nouvelles stratégies thérapeutiques. Le Récepteur à Domaine Discoïdine de… (more)

▼

Les maladies rénales ont un impact socio-économique majeur sur la santé publique nécessitant le développement de nouvelles stratégies thérapeutiques. Le Récepteur à Domaine Discoïdine de type 1 (DDR1) est un récepteur non-intégrine des collagènes, à activité tyrosine-kinase. Son expression anormale est un facteur clé de la pathologie rénale qui promeut le développement de l’inflammation et de la fibrose.Ces travaux de thèse nous ont permis de démontrer que l'inhibition de DDR1 freinait la progression des maladies rénales dans trois modèles, dont l'un d'évolution aiguë, l'ischémie-reperfusion (I/R). Après I/R, les cellules épithéliales tubulaires proximales (CETP) exprimaient anormalement DDR1 et l'inhibition de ce récepteur empêchait l'acquisition d'un phénotype pro-inflammatoire par ce type cellulaire. Nous avons démontré in vitro que le stress du réticulum endoplasmique (RE), secondaire à l'hypoxie, était responsable de l'induction de DDR1, via l'activation du facteur de transcription CHOP. De plus, le profil d'expression de DDR1 dans des biopsies de patients transplantés était similaire à celui obtenu dans l'I/R expérimentale.Enfin, les résultats préliminaires obtenus dans un nouveau modèle de souris triples transgéniques ont montré l'installation d'une inflammation et d'une fibrose rénales secondaires à la surexpression génétiquement définie de DDR1 durant 4 semaines dans les cellules épithéliales tubulaires.En conclusion, nos résultats suggèrent que la surexpression de DDR1 joue un rôle délétère dans les néphropathies chroniques et aiguës, ce qui renforce l’intérêt du développement d’inhibiteurs spécifiques de DDR1 capables de bloquer la fonction de ce récepteur.

Renal diseases lead to severe long-term complications of kidney function and only few preventive and therapeutic options exist. Discoidin Domain Receptor 1 (DDR1) is a non-integrin collagen receptor expressed in several cell types within the kidney. Its abnormal expression has a deleterious role in experimental chronic kidney diseases (CKD) by promoting renal inflammation and fibrosis.The inhibition of DDR1 stopped the progression of renal disease in two models of experimental CKD and protected renal function and structure in a model of acute kidney disease, ischemia-reperfusion (I/R). DDR1 expression was strongly induced in proximal epithelial tubular cells (PETCs) after I/R. Moreover, isolated PETCs from DDR1 heterozygous mice after I/R did not acquire the pro-inflammatory phenotype displayed by PETCs from WT mice. Endoplasmic reticulum (ER) stress was responsible for DDR1 pathological expression in hypoxic PETCs after I/R through the activation of CHOP transcription factor. Interestingly, biopsies of transplant patients with prolonged ischemia during transplantation had a very similar expression profile of DDR1 in proximal tubules as in experimental I/R.Finally, DDR1 overexpression in epithelial tubular cells for four weeks, in a new conditional transgenic mouse model, led to the development of renal inflammation and fibrosis.To conclude, our…

Advisors/Committee Members: Chatziantoniou, Christos (thesis director), Dussaule, Jean-Claude (thesis director).

Subjects/Keywords: DDR1; Néphropathies; Cible thérapeutique; Inflammation; Fibrose; Stress du réticulum endoplasmique; Discoidin Domain Receptor 1 (DDR1); Renal diseases; Fibrosis; Therapeutic target; Ischemia-Reperfusion; 616.61

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dorison, A. (2016). Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2016PA066144

Chicago Manual of Style (16^th Edition):

Dorison, Aude. “Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases.” 2016. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed January 22, 2021. http://www.theses.fr/2016PA066144.

MLA Handbook (7^th Edition):

Dorison, Aude. “Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases.” 2016. Web. 22 Jan 2021.

Vancouver:

Dorison A. Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2016. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2016PA066144.

Council of Science Editors:

Dorison A. Le récepteur à domaine discoïdine de type 1 : un acteur majeur des pathologies rénales chroniques et aiguës : The discoidin domain receptor 1 : a key mediator of chronic and acute kidney diseases. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2016. Available from: http://www.theses.fr/2016PA066144

University of Toronto

10. Xu, Songyi. N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases.

Degree: PhD, 2020, University of Toronto

URL: http://hdl.handle.net/1807/101328

► N-cadherin mediates cell-cell contacts in vascular smooth muscle cells (VSMCs) and regulates VSMC behaviours. Discoidin domain receptor 1 (DDR1) is a collagen binding receptor also… (more)

▼ N-cadherin mediates cell-cell contacts in vascular smooth muscle cells (VSMCs) and regulates VSMC behaviours. Discoidin domain receptor 1 (DDR1) is a collagen binding receptor also implicated in these processes. Previous studies showed that both N-cadherin and DDR1 are upregulated after vascular injury, but it is not known whether the two molecules are associated. The ability to establish proper N-cadherin junctions is important in regulating VSMC behaviour. In my studies, I found that N-cadherin could associate with DDR1, and that this association was increased during VSMC migration and wound closure. I found that N-cadherin was reduced in lipid rafts and mislocalized from cell-cell junctions in the absence of DDR1. Disruption of lipid rafts by cholesterol oxidase or methyl-β-cyclodextrin removed N-cadherin from lipid rafts of DDR1+/+ VSMCs and disrupted N-cadherin contacts, and these effects were reversed by cholesterol rescue that restored lipid rafts. Knockdown of DDR1 by siRNA resulted in mislocalized N-cadherin contacts from cell junctions, and transfection of DDR1-/- VSMCs with full-length DDR1 rescued the formation of N-cadherin junctions. The mislocalization of N-cadherin contacts in DDR1-/- VSMCs was also accompanied by disruption of the actin cytoskeleton. N-cadherin contacts in VSMCs undergo constant remodeling, especially during disease processes. Calcium switch to disrupt and restore contacts did not affect N-cadherin triton solubility in DDR1+/+ and DDR1-/- VSMCs or the association between N-cadherin and DDR1. While collagen stimulation of DDR1 increased the association between N-cadherin and DDR1 in cells with mature, well-established cell contacts, it did not affect N-cadherin localization, its triton solubility, or the association between N-cadherin and DDR1 during contact disruption, restoration, and wound closure. Rho GTPases are master regulators of the cytoskeleton and can mediate cytoskeletal processes downstream of cell-cell contacts. Using calcium switch and plating on either IgG or N-cadherin-Fc coated surfaces, active Rho GTPase pull-down assays showed a consistent decrease in Cdc42 and RhoA activity after N-cadherin contact establishment in DDR1+/+ SMCs. Overall, these data reveal that N-cadherin cell-cell contacts in VSMCs can be regulated through interaction with DDR1 and localization in lipid rafts, and that the establishment of N-cadherin contacts can suppress Rho GTPase activity. Advisors/Committee Members: Bendeck, Michelle, Laboratory Medicine and Pathobiology.

Subjects/Keywords: Cell-cell interaction; DDR1; N-cadherin; Rho GTPases; Vascular smooth muscle cells; 0307

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xu, S. (2020). N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/101328

Chicago Manual of Style (16^th Edition):

Xu, Songyi. “N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases.” 2020. Doctoral Dissertation, University of Toronto. Accessed January 22, 2021. http://hdl.handle.net/1807/101328.

MLA Handbook (7^th Edition):

Xu, Songyi. “N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases.” 2020. Web. 22 Jan 2021.

Vancouver:

Xu S. N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases. [Internet] [Doctoral dissertation]. University of Toronto; 2020. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1807/101328.

Council of Science Editors:

Xu S. N-cadherin Regulation of Vascular Smooth Muscle Cells; the Role of DDR1 and Rho GTPases. [Doctoral Dissertation]. University of Toronto; 2020. Available from: http://hdl.handle.net/1807/101328

Vanderbilt University

11. Kothiwale, Sandeepkumar Kailas. A novel knowledge based conformation sampling algorithm and applications in drug discovery.

Degree: PhD, Chemistry, 2016, Vanderbilt University

URL: http://hdl.handle.net/1803/13765

► Computational approaches have become important tools in drug discovery. Computational technologies have been developed for application in all aspects of the drug discovery process including… (more)

Subjects/Keywords: computational drug discovery; kinase selectivity; quantitative structure activity relationships; backpropagation algorithm; machine learning; knowledge-based; cheminformatics; conformational sampling; DDR1 kinase; neural networks; homology modelling

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kothiwale, S. K. (2016). A novel knowledge based conformation sampling algorithm and applications in drug discovery. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13765

Chicago Manual of Style (16^th Edition):

Kothiwale, Sandeepkumar Kailas. “A novel knowledge based conformation sampling algorithm and applications in drug discovery.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/13765.

MLA Handbook (7^th Edition):

Kothiwale, Sandeepkumar Kailas. “A novel knowledge based conformation sampling algorithm and applications in drug discovery.” 2016. Web. 22 Jan 2021.

Vancouver:

Kothiwale SK. A novel knowledge based conformation sampling algorithm and applications in drug discovery. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/13765.

Council of Science Editors:

Kothiwale SK. A novel knowledge based conformation sampling algorithm and applications in drug discovery. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/13765

12. Blissett, Angela Rae. Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors.

Degree: PhD, Biophysics, 2011, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1305900854

► Bone remodeling impacts the material and structural composition of bone, both which are determinants of tissue strength. The underlying mechanisms involved in bone remodeling are… (more)

▼ Bone remodeling impacts the material and structural composition of bone, both which are determinants of tissue strength. The underlying mechanisms involved in bone remodeling are not fully understood. Collagen type 1 is the major component of bone; therefore, processes that regulate collagen deposition and ultrastructure will likely impact bone quality. Discoidin domain receptors (DDR1 and DDR2) are ubiquitously expressed transmembrane proteins that bind to and get activated by collagens, including collagen type I. DDR receptor activation is known to regulate numerous cellular functions including differentiation, migration, cell cycle control and extracellular matrix (ECM) remodeling. This thesis explores the role of DDR1 and DDR2 in bone formation and remodeling. We hypothesize that the expression of DDR extracellular domain (ECD) inhibits collagen fibrillogenesis and alters collagen matrix mineralization. Our aim was to understand how DDR ECD expression impacts the morphology of collagen matrices assembled by osteoblasts in cell culture. To address this, we created stably transfected pre-osteoblast cell lines which express various ECD-containing isoforms of DDRs. Cells were cultured in the presence of ascorbic acid to facilitate production of matrix proteins and prepared for assessment by transmission electron microscopy (TEM). We found that samples over-expressing DDR ECD exhibit collagen matrices with smaller fiber diameters, disrupted banded structures, reduced matrix deposition, delayed fibrillogenesis and increased matrix mineralization as compared to nontransfected controls. Based on our findings, we conclude that DDR ECDs are inhibitors of collagen fibrillogenesis and promote matrix mineralization. In addition, we hypothesized that DDR1 regulates the differentiation and function of bone cells such as osteoblasts and osteoclasts. Utilizing TEM we observed the abundance of osteoblasts and osteocytes (bone forming cells) and the ultrastructure of the collagen matrix in cortical bone from wildtype and DDR1 knockout (KO) mice. We found that cortical bone from DDR1 KO mice contained far fewer osteoblastic cells and collagen fibers with increased fiber diameters as compared to wildtype. To assess osteoclast differentiation, we isolate primary monocytes from wildtype and DDR1 KO mice. Isolated cells were cultured in media containing M-CSF and RANKL to determine rate of osteoclast differentiation. Further, we seeded multinucleated wildtype and DDR1-/- osteoclasts onto ivory substrates (which mimics bone) to observe resorption efficiency. We found that DDR1-/- pre-osteoclasts exhibited a slower rate of differentiation and that DDR1-/- osteoclasts resorb at a slower rate as compared to wildtype cells. Lastly, we hypothesized that DDR1 expression regulates bone microarchitecture. We employed μ-CT analysis on femurs isolated from wildtype and DDR1 KO mice in order to quantitatively assess various parameters for cortical and trabecular bone. We find that DDR1 KO mice exhibited femurs with reduced mass indicative of bone… Advisors/Committee Members: Agarwal, Gunjan (Committee Chair).

Subjects/Keywords: Biomedical Research; Biophysics; collagen; bone; extracellular matrix; DDR1; DDR2

…fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2. J Mol Biol. 395: p… …30 CHAPTER 2: Extracellular Domains of DDR1 and DDR2 Regulate Collagen Fibrillogenesis and… …Discussion �� ...62 CHAPTER 3: DDR1 Regulates Differentiation and Function of… …89 CHAPTER 4: DDR1 Regulates Bone Microarchitecture �� …95 Aim and Rationale… …DDR1 and DDR2 inhibit collagen fibrillogenesis �� .115 DDR1 and DDR2 promote matrix…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Blissett, A. R. (2011). Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1305900854

Chicago Manual of Style (16^th Edition):

Blissett, Angela Rae. “Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors.” 2011. Doctoral Dissertation, The Ohio State University. Accessed January 22, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1305900854.

MLA Handbook (7^th Edition):

Blissett, Angela Rae. “Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors.” 2011. Web. 22 Jan 2021.

Vancouver:

Blissett AR. Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors. [Internet] [Doctoral dissertation]. The Ohio State University; 2011. [cited 2021 Jan 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1305900854.

Council of Science Editors:

Blissett AR. Regulation of Extracellular Matrix Remodeling and Bone Morphology by Discoidin Domain Receptors. [Doctoral Dissertation]. The Ohio State University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1305900854

The Ohio State University

13. Flynn, Lisa A. Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells.

Degree: MS, Biomedical Engineering, 2009, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1242766133

► Discoidin Domain Receptors (DDRs) are unique members of the Receptor Tyrosine Kinases (RTKs) family. Most RTKs are activated by soluble proteins present in bodily… (more)

Subjects/Keywords: Biomedical Research; Cellular Biology; DDR1; DDR2; collagen fibrillogenesis; DDR extracellular domain

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Flynn, L. A. (2009). Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1242766133

Chicago Manual of Style (16^th Edition):

Flynn, Lisa A. “Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells.” 2009. Masters Thesis, The Ohio State University. Accessed January 22, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242766133.

MLA Handbook (7^th Edition):

Flynn, Lisa A. “Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells.” 2009. Web. 22 Jan 2021.

Vancouver:

Flynn LA. Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells. [Internet] [Masters thesis]. The Ohio State University; 2009. [cited 2021 Jan 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1242766133.

Council of Science Editors:

Flynn LA. Inhibition of Collagen Fibrillogenesis Upon Secretion of Extracellular Domains of DDR1 and DDR2 by Cells. [Masters Thesis]. The Ohio State University; 2009. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1242766133

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations