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You searched for +publisher:"Vanderbilt University" +contributor:("Andrew J. Link, Ph.D."). Showing records 1 – 2 of 2 total matches.

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Vanderbilt University

1. Spurlock III, Charles Floyd. Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints.

Degree: PhD, Microbiology and Immunology, 2014, Vanderbilt University

Rheumatoid arthritis is the most common serious autoimmune disease affecting almost one percent of the human population worldwide. Methotrexate is the most commonly used disease-modifying agent in patients with rheumatoid arthritis. Despite decades-long experience with the use of methotrexate in this disease, the mechanisms responsible for its activity in rheumatoid arthritis are not very well understood. Through a series of biochemical approaches and in vivo studies in patients with rheumatoid arthritis, we have defined two novel pathways contributing to the anti-inflammatory effects of methotrexate in T cells. The first pathway is dependent upon blockade of tetrahydropbiopterin biosynthesis resulting in increased activation of c-Jun-N-terminal kinase, restoration of cell cycle checkpoint deficiencies, and reduced levels of nuclear factor kappa B, a master regulator of inflammation. Finally, we also discovered that methotrexate induces expression of the long, intergenic non-coding RNA, lincRNA-p21. Independent of methotrexate-mediated blockade of tetrahydrobiopterin and increased activity of c-Jun-N-terminal kinase, induction of lincRNA-p21 by methotrexate also reduces indices of inflammation via blockade of nuclear factor kappa B activity. Thus, multiple pathways are responsible for the immunomodulatory effects of methotrexate in the treatment of rheumatoid arthritis. Advisors/Committee Members: Subramaniam Sriram, M.B., B.S. (committee member), Jonathan M. Irish, Ph.D. (committee member), Amy S. Major, Ph.D. (committee member), Andrew J. Link, Ph.D. (chair), Thomas M. Aune, Ph.D. (committee member).

Subjects/Keywords: methotrexate; autoimmune disease; inflammation; rheumatoid arthritis; cell cycle checkpoints; c-Jun-N-terminal kinase; p53; tetrahydrobiopterin; long non-coding RNA

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

APA (6th Edition):

Spurlock III, C. F. (2014). Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu//available/etd-03212014-091439/ ;

Chicago Manual of Style (16th Edition):

Spurlock III, Charles Floyd. “Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed April 21, 2019. http://etd.library.vanderbilt.edu//available/etd-03212014-091439/ ;.

MLA Handbook (7th Edition):

Spurlock III, Charles Floyd. “Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints.” 2014. Web. 21 Apr 2019.

Vancouver:

Spurlock III CF. Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2019 Apr 21]. Available from: http://etd.library.vanderbilt.edu//available/etd-03212014-091439/ ;.

Council of Science Editors:

Spurlock III CF. Methotrexate and Rheumatoid Arthritis: At the Crossroads Between Inflammation and Defects in Cell Cycle Checkpoints. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://etd.library.vanderbilt.edu//available/etd-03212014-091439/ ;


Vanderbilt University

2. Samir, Parimal. Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms.

Degree: PhD, Biochemistry, 2016, Vanderbilt University

I studied three problems in my dissertation research. In the first study, I built a conceptual basis for understanding the cellular responses to multiple concurrent stimuli. A gene represents the inherent information of the cells while a stimulus represents the information outside their boundary. Since a gene and a stimulus are both packets of information, they can be considered analogues. This assumption allowed me to define the concepts of environmental interactions and environmental epistasis in terms of gene interactions and genetic epistasis. I used proteomic and transcriptomic changes in Saccharomyces cerevisiae to test the conceptual framework. In the second study, I designed and performed experiments to test the ribosome filter hypothesis. The ribosome filter hypothesis states that the amount of information flow from the transcriptome to the proteome is regulated by the composition of ribosomes. A difference in the protein composition of ribosomes from cells growing in two different conditions was evidence supporting the ribosome filter hypothesis. I used growth of S. cerevisiae with fermentable carbon source, glucose, and non-fermentable carbon source, glycerol, as the two conditions. I used iTRAQ labeling based quantitative proteomics and, in collaboration with the Joachim Frank lab, cryo-electron microscopy to measure the changes in the protein composition of ribosomes. It allowed identification of candidate ribosomal proteins that regulate the information flow from specific transcripts. I used yeast genetics and polysome profiling to measure the effect of loss of function of a candidate ribosomal protein paralog pair, Rpl8a or Rpl8b, on translation. In the third project, I studied the changes introduced in the skeletal muscle proteome of myotonic dystrophy patients, both DM1 and DM2, due to the disruption of information flow by microsatellite repeat expansions in the non-coding regions of mRNA transcripts. I used iTRAQ labeling based quantitative proteomics analysis to quantitate the changes in the skeletal muscle proteome of DM patients compared to healthy volunteers. I identified differentially present proteins and used pathway analysis to understand their role in the pathogenesis. In summary, I have studied three different ways the information content of cells and tissues are affected. Advisors/Committee Members: Andrew J. Link Ph.D. (chair), Melani D. Ohi Ph.D. (committee member), Nicholas J. Reiter Ph.D. (committee member), Kevin L. Schey Ph.D. (committee member), William P. Tansey Ph.D. (committee member).

Subjects/Keywords: Systems Biology; Proteomics; Translational Control; Environmental Interactions; Environmental Epistasis; Myotonic Dystrophy; Ribosome Filter Hypothesis; Ribosome Code; Specialized Ribosome

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

APA (6th Edition):

Samir, P. (2016). Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu//available/etd-03182016-094404/ ;

Chicago Manual of Style (16th Edition):

Samir, Parimal. “Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed April 21, 2019. http://etd.library.vanderbilt.edu//available/etd-03182016-094404/ ;.

MLA Handbook (7th Edition):

Samir, Parimal. “Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms.” 2016. Web. 21 Apr 2019.

Vancouver:

Samir P. Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2019 Apr 21]. Available from: http://etd.library.vanderbilt.edu//available/etd-03182016-094404/ ;.

Council of Science Editors:

Samir P. Systems Analysis of Eukaryotic Proteomic Regulatory Mechanisms. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://etd.library.vanderbilt.edu//available/etd-03182016-094404/ ;

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