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Georgia Tech
1.
Bachman, Haylee N.
Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.
Degree: PhD, Chemistry and Biochemistry, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60669 
► Recombinant proteins which mimic fibronectin’s (Fn’s) integrin binding domain in conformationally stable and unfolded states are investigated to explore integrin specificity and downstream phenotypic differences…
(more)
▼ Recombinant proteins which mimic fibronectin’s (Fn’s) integrin binding domain in conformationally stable and unfolded states are investigated to explore integrin specificity and downstream phenotypic differences on lung fibroblasts. The recombinant protein expression and purification systems are redesigned for optimization and ease of isolation. Protein purification is validated and protein function is confirmed. These recombinant proteins are then used to explore biological function such as differential integrin engagement and focal adhesion associated signaling proteins. The “integrin-switch” behavior is characterized, focal adhesion quality is investigated, and force-mediated focal adhesion components FAK and Src are observed for phosphorylation in combination with recombinant variant Fn fragments. Lung fibroblast phenotype is examined based on the conformational bias of Fn’s integrin binding domain as well. Evalutation of cell contractility is explored via cell shape and size. Cell proliferation and etabolism are assessed to determine differences based on Fn fragment conformation presentation. The myfibroblast indicator of MRTF nuclear translocation is calculated to define how myo-like lung fibroblasts are with differential integrin engagement. These findings suggest that by mimicking stable vs unfolded conformations of Fn’s IBD different integrins are engaged and downstream cell behavior is affected. There appears to be a temporal relationship between lung fibroblasts and their substrate exposure which may cause phenotype changes that lead to myofibroblast dysregulation.
Advisors/Committee Members: Finn, M. G. (advisor), Williams, Loren (committee member), Barry, Bridgette (committee member), Lam, Wilbur (committee member).
Subjects/Keywords: Fibronectin; Integrin; Mechanobiology; Matrix biology; Extracellular matrix
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APA (6th Edition):
Bachman, H. N. (2017). Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60669
Chicago Manual of Style (16th Edition):
Bachman, Haylee N. “Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60669.
MLA Handbook (7th Edition):
Bachman, Haylee N. “Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences.” 2017. Web. 11 Apr 2021.
Vancouver:
Bachman HN. Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60669.
Council of Science Editors:
Bachman HN. Exploring fibronectin's integrin binding domain effects on lung fibroblast integrin specificity and downstream phenotypic differences. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60669
Georgia Tech
2.
Ingram, Rena.
Label-free bioanalytical methods for investigating bimolecular interactions: A review.
Degree: MS, Chemistry and Biochemistry, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/62606
► Interactions between biological molecules such as DNA, RNA, protein, lipids, and carbohydrates are critical to the understanding of all biological, physical, and chemical processes such…
(more)
▼ Interactions between biological molecules such as DNA, RNA, protein, lipids, and carbohydrates are critical to the understanding of all biological, physical, and chemical processes such as protein function, disease diagnosis, and drug discovery.1 Most of the techniques currently used to detect and quantify biomolecular interactions are assisted by foreign molecules that are either permanently or temporarily attached to the molecule of interest; such labels most often fluorescence, luminescence, are radioactive, or are large enough to be easily detected (nanoparticles).2 Fluorescent labeling detection methods, the most common and convenient, are attractive due to their stability, easy manipulation, and high sensitivity and dynamic range.2 However, label-free and real-time detection methods are of high demand due to a number of potential disadvantages of the labels or the methods used to attach them: 1) altering the structure, conformation, or functional properties of the biomolecule of interest, 2) occupying the active site(s) of biomolecules thereby changing their binding affinity, 3) producing false-positive results by interacting with unanticipated components, 4) loss of sample during the labeling and purification process, 5) high sensitivity to changes in environmental conditions, and 6) potential to be tedious and expensive.
Advisors/Committee Members: Oyelere, Adegboyega (advisor), Finn, M. G. (committee member), Fernandez, Facundo (committee member), Gaucher, Eric (committee member), Wu, Ronghu (committee member).
Subjects/Keywords: Label-free; Label-required; Isothermal titration calorimetry; Surface plasmon resonance; Backscattering interferometry; Bio-layer interferometry; Field-effect transistor-based biosensors; Magnetoelastic biosensors; Biophotonic biosensors
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APA (6th Edition):
Ingram, R. (2017). Label-free bioanalytical methods for investigating bimolecular interactions: A review. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62606
Chicago Manual of Style (16th Edition):
Ingram, Rena. “Label-free bioanalytical methods for investigating bimolecular interactions: A review.” 2017. Masters Thesis, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/62606.
MLA Handbook (7th Edition):
Ingram, Rena. “Label-free bioanalytical methods for investigating bimolecular interactions: A review.” 2017. Web. 11 Apr 2021.
Vancouver:
Ingram R. Label-free bioanalytical methods for investigating bimolecular interactions: A review. [Internet] [Masters thesis]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/62606.
Council of Science Editors:
Ingram R. Label-free bioanalytical methods for investigating bimolecular interactions: A review. [Masters Thesis]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/62606
Georgia Tech
3.
Hogan, Scott R.
Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications.
Degree: PhD, Chemistry and Biochemistry, 2020, Georgia Tech
URL: http://hdl.handle.net/1853/62721
► The primary focus of this thesis centers around the examination of lipids to aid in the diagnosis, prognosis, and mechanistic understanding of traumatic brain injury…
(more)
▼ The primary focus of this thesis centers around the examination of lipids to aid in the diagnosis, prognosis, and mechanistic understanding of traumatic brain injury (TBI). Lipids are important signaling molecules and play a critical role in energy storage as well as membrane structure and organization. Using mass spectrometry (MS) based methods to perform non-targeted metabolomic experiments with a focus on extraction of lipid metabolites, a rodent model is investigated to explore the feasibility of developing lipid biomarker panels to classify injury post-hoc across multiple severities. The developed methods are then used to study another biological system in order to show the broad applicability of lipidomics by investigating the effect of Karenia brevis allelopathy on two phytoplankton competitors.
Advisors/Committee Members: Fernández, Facundo M. (advisor), LaPlaca, Michelle (advisor), Finn, M. G. (committee member), Merrill, Alfred (committee member), Garg, Neha (committee member).
Subjects/Keywords: Traumatic brain injury; Biomarkers; Lipids; Mass spectrometry; Lipidomics
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APA (6th Edition):
Hogan, S. R. (2020). Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62721
Chicago Manual of Style (16th Edition):
Hogan, Scott R. “Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications.” 2020. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/62721.
MLA Handbook (7th Edition):
Hogan, Scott R. “Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications.” 2020. Web. 11 Apr 2021.
Vancouver:
Hogan SR. Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications. [Internet] [Doctoral dissertation]. Georgia Tech; 2020. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/62721.
Council of Science Editors:
Hogan SR. Utilization of mass spectrometric techniques to identify novel lipid biomarkers of traumatic brain injury and other practical applications. [Doctoral Dissertation]. Georgia Tech; 2020. Available from: http://hdl.handle.net/1853/62721
Georgia Tech
4.
Zhu, Guanghui.
Formation mechanism, defect engineering and applications of porous organic cages.
Degree: PhD, Chemical and Biomolecular Engineering, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/62210
► This thesis presents a systematic study from fundamental to applied aspects of porous organic cages aiming at pushing porous organic cage materials towards designed structure…
(more)
▼ This thesis presents a systematic study from fundamental to applied aspects of porous organic cages aiming at pushing porous organic cage materials towards designed structure and functionality for targeted applications. This thesis starts with detailed investigation of the formation mechanisms of imine-based POCs and implying new design strategies for POCs. The formation mechanism study closed the loop for in silico design and prediction for POCs. The properties of POCs are tuned by defect engineering for better CO2 affinity or acid gas stability, which are first steps towards industrial application. Two proof-of-concept applications in both adsorptive and membrane-based separations are demonstrated with the use of amorphous POCs. The findings of this thesis can be extended in various directions such as computational guided design and synthesis, properties modification, and targeted applications, which will drive the POCs research area forward.
Advisors/Committee Members: Lively, Ryan P. (advisor), Jones, Christopher W. (advisor), Sholl, David S. (committee member), Finn, M. G. (committee member), Meredith, J. Carson (committee member).
Subjects/Keywords: Separation; Adsorption; Membrane; Porous material
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APA (6th Edition):
Zhu, G. (2018). Formation mechanism, defect engineering and applications of porous organic cages. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62210
Chicago Manual of Style (16th Edition):
Zhu, Guanghui. “Formation mechanism, defect engineering and applications of porous organic cages.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/62210.
MLA Handbook (7th Edition):
Zhu, Guanghui. “Formation mechanism, defect engineering and applications of porous organic cages.” 2018. Web. 11 Apr 2021.
Vancouver:
Zhu G. Formation mechanism, defect engineering and applications of porous organic cages. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/62210.
Council of Science Editors:
Zhu G. Formation mechanism, defect engineering and applications of porous organic cages. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62210
Georgia Tech
5.
Beveridge, Jennifer Marie.
Click chemistry applications for surfaces.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/62216
► Copper(I) catalyzed azide alkyne cycloaddition (CuAAC) is a powerful tool that allows for diverse functionalization from azide and alkyne precursors. This research probed the kinetics…
(more)
▼ Copper(I) catalyzed azide alkyne cycloaddition (CuAAC) is a powerful tool that allows for diverse functionalization from azide and alkyne precursors. This research probed the kinetics of the CuAAC reaction in- and between- lipid membranes, as well as used it to modify SU-8 and flexible PVC polymers post-polymerization while maintain key polymer properties. For membranes, this research demonstrated the comparability of in-membrane kinetics to in-solution kinetics, and saw reactivity in and between membranes comparable to reactivity previously documented in the literature for a different lipid system. For flexible PVC, azidation was completed with the aid of phase transfer catalysts, and subsequent CuAAC was performed. For SU-8 surfaces, azidation of epoxides remaining after photo-crosslinking and subsequent CuAAC demonstrate a broad array of potential functionalization. These applications make click chemistry relevant to materials in new ways and will allow for the derivatization of these materials that is limited only by the user’s creativity.
Advisors/Committee Members: Finn, M. G. (advisor), Oyelere, Adegboyega (committee member), Lieberman, Raquel (committee member), Wu, Ronghu (committee member), Sievers, Carsten (committee member).
Subjects/Keywords: Click chemistry; Flexible PVC; SU-8 azidation; Vesicle reactivity
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APA (6th Edition):
Beveridge, J. M. (2018). Click chemistry applications for surfaces. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62216
Chicago Manual of Style (16th Edition):
Beveridge, Jennifer Marie. “Click chemistry applications for surfaces.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/62216.
MLA Handbook (7th Edition):
Beveridge, Jennifer Marie. “Click chemistry applications for surfaces.” 2018. Web. 11 Apr 2021.
Vancouver:
Beveridge JM. Click chemistry applications for surfaces. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/62216.
Council of Science Editors:
Beveridge JM. Click chemistry applications for surfaces. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62216
Georgia Tech
6.
Gerberich, Brandon.
Targeted collagen photocrosslinking for treatment of glaucoma.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2020, Georgia Tech
URL: http://hdl.handle.net/1853/62838
► Glaucoma is the leading cause of irreversible blindness worldwide and has a complex etiology associated with elevated intraocular pressure. Biomechanical forces induce vision loss through…
(more)
▼ Glaucoma is the leading cause of irreversible blindness worldwide and has a complex etiology associated with elevated intraocular pressure. Biomechanical forces induce vision loss through strain-induced damage to the retinal ganglion cells conducting visual information from the retina to the brain. This work tests the hypothesis that stiffening the peripapillary scleral (collagenous tissue adjacent to the optic nerve) protects against glaucomatous vision loss. A photocrosslinking approach was 1) developed to selectively stiffen the peripapillary sclera in vivo, 2) tested for efficacy in a rat animal model of glaucoma, and 3) simulated using a computational model to predict optimal photocrosslinking parameters. Scleral photocrosslinking was successfully targeted to the peripapillary sclera in vivo and found to have moderate treatment toxicity. In vivo studies in glaucomatous rats revealed that our treatment did not worsen glaucomatous damage contrary to a previous study. Computational modeling predicted key treatment parameter values and showed that crosslinking is most sensitive to tissue rather than sensitizer properties. Together, this body of work demonstrates the feasibility of using targeted scleral photocrosslinking as a potential future treatment of glaucoma.
Advisors/Committee Members: Prausnitz, Mark (advisor), Ethier, C. Ross (committee member), Pardue, Machelle (committee member), Costarides, Anastasios (committee member), Finn, M. G. (committee member).
Subjects/Keywords: Collagen crosslinking; Photocrosslinking; Eye; Glaucoma; Methylene blue; Scleral stiffening; Peripapillary sclera; Biomechanics
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APA (6th Edition):
Gerberich, B. (2020). Targeted collagen photocrosslinking for treatment of glaucoma. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62838
Chicago Manual of Style (16th Edition):
Gerberich, Brandon. “Targeted collagen photocrosslinking for treatment of glaucoma.” 2020. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/62838.
MLA Handbook (7th Edition):
Gerberich, Brandon. “Targeted collagen photocrosslinking for treatment of glaucoma.” 2020. Web. 11 Apr 2021.
Vancouver:
Gerberich B. Targeted collagen photocrosslinking for treatment of glaucoma. [Internet] [Doctoral dissertation]. Georgia Tech; 2020. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/62838.
Council of Science Editors:
Gerberich B. Targeted collagen photocrosslinking for treatment of glaucoma. [Doctoral Dissertation]. Georgia Tech; 2020. Available from: http://hdl.handle.net/1853/62838
Georgia Tech
7.
Meyer, Travis.
Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63548
► Processes that occur at the nanoscale are the foundational building blocks of our world. As such, there is considerable interest in ways to study and…
(more)
▼ Processes that occur at the nanoscale are the foundational building blocks of our world. As such, there is considerable interest in ways to study and manipulate matter at this scale, with applications in biomedicine and other fields. DNA origami has emerged over the past decade as a promising technology for nanofabrication, offering the capacity for precise and tunable nanoscale synthesis while maintaining the ease and scale of bottom-up self-assembly. The goal of this work is to develop novel ways in which DNA origami can be used to manipulate nanoscale processes. To this end, I developed a single DNA origami nanorod which is used in two distinct studies, highlighting the multifunctionality of this structure. I first investigated the effect of iron oxide nanoparticle clustering on MRI contrast generation by organizing particles in precise patterns on the nanorod. I found that small changes in the number of attached iron oxide nanoparticles lead to significant enhancement in T2 relaxivity, while inter-particle spacing has a minimal effect. In the second part of thesis, I developed the first DNA origami molecular motor, which converts chemical energy into mechanical activity and demonstrates autonomous directed motion over micron distances. By leveraging the unique addressability of DNA origami, I found that these motors predominately exhibit a rolling motion and that this behavior can be tuned via small alterations to the nanorod. Combined, this work demonstrates two novel applications for DNA origami nanostructures. We expect this work will serve as an initial platform for further studies and open up a range of new possibilities for the use of DNA origami as MRI contrast agents and molecular motors.
Advisors/Committee Members: Ke, Yonggang (advisor), Bao, Gang (advisor), Finn, M. G. (committee member), Xia, Younan (committee member), Kwong, Gabe (committee member), Mao, Hui (committee member).
Subjects/Keywords: DNA origami; DNA motors; Iron oxide nanoparticles
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APA (6th Edition):
Meyer, T. (2019). Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63548
Chicago Manual of Style (16th Edition):
Meyer, Travis. “Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/63548.
MLA Handbook (7th Edition):
Meyer, Travis. “Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes.” 2019. Web. 11 Apr 2021.
Vancouver:
Meyer T. Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/63548.
Council of Science Editors:
Meyer T. Engineering a multi-functional DNA origami nanorod for the control of nanoscale processes. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63548
Georgia Tech
8.
Liu, Jiaying.
Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63551
► Monoclonal antibodies (mAbs) have shown great promise as immunotherapy of cancer in the past decades. They mediate the antibody-dependent immune responses to eliminate the malignant…
(more)
▼ Monoclonal antibodies (mAbs) have shown great promise as immunotherapy of cancer in the past decades. They mediate the antibody-dependent immune responses to eliminate the malignant or suppressive cells and proteins and restore anti-cancer immunity. However, the application of monoclonal antibodies as therapeutics is greatly hampered by its high production cost as well as high dosage required to generate significant therapeutic effect due to limited tissue penetration and retention. Additionally, monoclonal antibodies targeting some important immunological targets, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, are still waiting to be developed. Here, we have developed a novel type of artificial antibodies, the synthetic nanoparticle antibodies (SNAbs), which are Janus nanoparticles multivalently displaying both binding ligands for the selected cellular targets and Fc-mimicking ligands that can activate Fc receptors. Our primary hypothesis is that the designed SNAbs could induce antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP) of cellular targets efficiently both in vitro and in vivo. A simple chemistry to fabricate Janus gold nanoparticles and to modify these nanoparticles with peptide ligands was designed to generate SNAbs. We evaluated the capability of SNAbs to target MDSCs, as a model cell type in both ex vivo assays and in vivo tumor model systems. We showed that SNAbs can selectively induce the antibody-dependent killing of MDSCs in the mixture of various types of cells and are also able to deplete MDSCs in a tumor model. The research completed in this thesis demonstrated that the SNAbs are a functional alternative to monoclonal antibodies and hold great promise as a potent immunotherapy for cancer.
Advisors/Committee Members: Roy, Krishnendu (advisor), Finn, M. G. (committee member), Guldberg, Robert (committee member), Kane, Ravi (committee member), Thomas, Susan (committee member).
Subjects/Keywords: Synthetic nanoparticle antibody; Immunotherapy; Cancer; Antibody-dependent immune responses
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APA (6th Edition):
Liu, J. (2019). Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63551
Chicago Manual of Style (16th Edition):
Liu, Jiaying. “Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/63551.
MLA Handbook (7th Edition):
Liu, Jiaying. “Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy.” 2019. Web. 11 Apr 2021.
Vancouver:
Liu J. Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/63551.
Council of Science Editors:
Liu J. Design and development of synthetic nanoparticle antibodies to deplete selected target cells for cancer immunotherapy. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63551
Georgia Tech
9.
Leleux, Jardin.
CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/59112
► Microbial pathogens range in size, shape, as well as biochemical and molecular properties. This has led to the evolution of a variety of pathogen recognition…
(more)
▼ Microbial pathogens range in size, shape, as well as biochemical and molecular properties. This has led to the evolution of a variety of pathogen recognition receptors (PRRs) in mammalian immune cells that are responsible for sensing pathogen-associated molecular patterns (PAMPs) and initiating specific types of immune responses. However, the breadth of the PRR responses, especially how dendritic cells sense pathogen physical properties in conjunction with specific molecular patterns and translate that into unique immune responses, remains unknown. Here, we have developed pathogen-like particles (PLPs) that mimic physical properties of large viruses or bacteria to demonstrate that CpG-mediated dendritic cell signaling can be precisely modulated by varying PLP parameters, specifically size and adjuvant density. We demonstrate controlled tunability of DC programming, allowing directed maturation of distinct T cell phenotypes, antibody class switching and in vivo immune-polarization. Furthermore, we show, for the first time, that the surface-density of CpG on PLPs can finely control DC signaling by regulating the kinetics of NFκB transcription and STAT3 phosphorylation. These findings suggest that DCs sense physical aspects of pathogen-like materials, broadening the tools that can be used to modulate immunity, better understand innate immune response mechanisms, and develop new and improved vaccines.
Advisors/Committee Members: Roy, Krishnendu (advisor), Finn, M. G. (committee member), Santagelo, Philip (committee member), Bellamkonda, Ravi (committee member), Thomas, Susan (committee member).
Subjects/Keywords: Dendritic cell; Immunit; Polymer particle; CpG
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APA (6th Edition):
Leleux, J. (2015). CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59112
Chicago Manual of Style (16th Edition):
Leleux, Jardin. “CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/59112.
MLA Handbook (7th Edition):
Leleux, Jardin. “CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization.” 2015. Web. 11 Apr 2021.
Vancouver:
Leleux J. CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/59112.
Council of Science Editors:
Leleux J. CpG-carrier size and density affects dendritic cell signaling, subset-tropism and systemic immune polarization. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/59112
Georgia Tech
10.
Raji, Idris.
Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors.
Degree: PhD, Chemistry and Biochemistry, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/59152
► Developing safer and/ or more effective chemotherapeutics has been a long-standing challenge in the drug discovery field. To address these shortcomings, the designed-multiple ligand (DML)…
(more)
▼ Developing safer and/ or more effective chemotherapeutics has been a long-standing challenge in the drug discovery field. To address these shortcomings, the designed-multiple ligand (DML) and targeted approaches were used to design novel series of histone deacetylase inhibitors (HDACi). Under the DML approach, bifunctional compounds capable of binding to both histone deacetylase and cyclooxygenase enzymes were made. A subset of the bifunctional compounds was significantly less toxic towards healthy cells compared to the US Food Drug and Administration (FDA) approved HDACi, vorinostat, despite their impressive anticancer profiles. On the other hand, the targeted approach was conceptualized to address the lack of efficacy in solid tumors seen with clinically approved HDACi. Two different series of compounds are reported herein as potential interventions in lung cancer and melanoma. In one of the series, clarithromycin- known for its preferential accumulation in lung tissues, was incorporated into the structures of HDACi to generate clarithromycin-targeted HDACi. With the eventual goal of achieving compounds that will preferentially localize in lung cancer tissues, the clarithromycin-targeted HDACi showed very good anticancer profiles in in vitro studies. The second series of compounds generated using the targeted approach are aimed as potential intervention in melanoma. In this approach, a template, known as benzamide, with high affinity for melanin, was incorporated into the design of HDACi. The benzamide compounds obtained showed some promise in melanoma cell lines, and warrant further studies to optimize for potency.
Advisors/Committee Members: Oyelere, Adegboyega K. (advisor), Finn, M. G. (committee member), France, Stefan (committee member), Bommarius, Andreas (committee member), Bellamkonda, Ravi (committee member).
Subjects/Keywords: Histone deacetylase; HDACi; Cyclooxygenase; Macrolide; Clarithromycin; Melanoma; Designed-multiple ligand; Lung cancer; Prostate cancer; Liposome; PGE2; NF-kB; Celecoxib; Indomethacin; Benzamides; Androgen receptor
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APA (6th Edition):
Raji, I. (2016). Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59152
Chicago Manual of Style (16th Edition):
Raji, Idris. “Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/59152.
MLA Handbook (7th Edition):
Raji, Idris. “Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors.” 2016. Web. 11 Apr 2021.
Vancouver:
Raji I. Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/59152.
Council of Science Editors:
Raji I. Novel approaches towards the discovery of tumor-selective histone deacetylase inhibitors. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/59152
Georgia Tech
11.
Crooke, Stephen Nicholas.
Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/60247
► Virus-like particles (VLPs) are multi-subunit protein assemblies that self-assemble into homogenous particles with periodic structure, making them ideal candidates for applications in biomedicine. This dissertation…
(more)
▼ Virus-like particles (VLPs) are multi-subunit protein assemblies that self-assemble into homogenous particles with periodic structure, making them ideal candidates for applications in biomedicine. This dissertation will discuss both the chemical and genetic modification of Qβ and PP7 VLPs for the design of vaccine platforms and drug delivery vehicles. Both the Qβ and PP7 VLPs are comprised of 180 copies of their respective coat protein (CP) monomers, which assemble to form icosahedral capsids of T = 3 geometry that are 28 and 30 nm in diameter, respectively. Herein, genetic engineering of the Qβ coat protein to introduce peptide and protein domains is described. First, these modifications were encoded as C-terminal extensions of the CP, and co-expression with unmodified subunits produced hybrid particles displaying the peptide or protein domains. These particles were successfully applied in both vaccination studies as well as the targeted delivery of prodrug-converting enzymes encapsulated within the VLP. To broaden the scope of targeting applications, the chemical conjugation of small molecules to the surface of Qβ VLPs was also used to direct cellular uptake and trafficking. The clearance of VLP delivery vehicles from circulation is an important factor governing their efficacy; to this effect, a survey of different polymer modifications and their effects on the immunological response to the Qβ VLP was undertaken. Lastly, PP7 VLPs were modified by genetically encoding extensions of a peptide implicated in mitigating phagocytic clearance to further explore strategies for prolonging circulation. All of the work presented here builds upon previous studies employing VLPs for drug delivery and vaccine development, while building upon the knowledge of chemical and genetic modifications that can be used to develop these materials. This work is poised to bring together the power of chemical and genetic modification in the development of nanoparticle platforms with novel properties that are equipped for effective vaccination and cellular targeting with reduced clearance in vivo.
Advisors/Committee Members: Finn, M. G. (advisor), Williams, Loren (committee member), Hud, Nicholas (committee member), Babensee, Julia (committee member), Thomas, Susan (committee member).
Subjects/Keywords: Virus-like particles; Drug delivery; Vaccine design; Prodrug therapy; Protein-polymer materials
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APA (6th Edition):
Crooke, S. N. (2018). Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60247
Chicago Manual of Style (16th Edition):
Crooke, Stephen Nicholas. “Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60247.
MLA Handbook (7th Edition):
Crooke, Stephen Nicholas. “Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery.” 2018. Web. 11 Apr 2021.
Vancouver:
Crooke SN. Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60247.
Council of Science Editors:
Crooke SN. Chemical and genetic modification of virus-like particles for applications in vaccine design and drug delivery. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/60247
Georgia Tech
12.
Williams, Corey Wayne.
Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/60299
► Complex carbocycles and heterocycles make up a large majority of natural product scaffolds and active pharmaceutical ingredient cores. As a result of this, developing methods…
(more)
▼ Complex carbocycles and heterocycles make up a large majority of natural product scaffolds and active pharmaceutical ingredient cores. As a result of this, developing methods to obtain such scaffolds in new, greener, and more modular ways remains an invaluable objective within the synthetic organic community. In this thesis, a number of exciting new methodologies have been developed to access some of these scaffolds, and significant progress is shown toward the application of these methodologies to access pharmaceutically-relevant cores: (1) a chemodivergent and catalytic interrupted, formal homo-Nazarov cyclization to access densely functionalized carbocycles, (2) the application of homo-Nazarov methodology toward the anticancer natural product, Propolisbenzofuran B, and (3) the application of Nazarov-like, Friedel- Crafts methodology toward the antimalarial natural product, Flinderole A. These methodological transformations are tolerant of a variety of functionalities, thus giving broad substrate scope. These syntheses seek to have modular key transformations that will allow formation of a wide variety of non-natural analogs, thus providing rapid access to a compound library useful in the study of structure-activity relationships.
Advisors/Committee Members: Collard, David M. (committee member), Finn, M. G. (committee member), Jones, Christopher W. (committee member), Oyelere, Adegboyega K. (committee member).
Subjects/Keywords: Cyclopropane; Homo-Nazarov; Nazarov; Synthetic methodology; Natural product synthesis; Ring-opening; Ring-closing; Cyclohexanone; Friedel-Crafts; Antimalarial; Anticancer; Propolisbenzofuran; Catalysis; Chemodivergence
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APA ·
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APA (6th Edition):
Williams, C. W. (2018). Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60299
Chicago Manual of Style (16th Edition):
Williams, Corey Wayne. “Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60299.
MLA Handbook (7th Edition):
Williams, Corey Wayne. “Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets.” 2018. Web. 11 Apr 2021.
Vancouver:
Williams CW. Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60299.
Council of Science Editors:
Williams CW. Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/60299
Georgia Tech
13.
Ehrenworth, Amy M.
Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae.
Degree: PhD, Chemistry and Biochemistry, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60672
► Alkaloids are a large group of plant natural products that have important therapeutic value. Because of their chemical complexity, therapeutic alkaloids are often obtained via…
(more)
▼ Alkaloids are a large group of plant natural products that have important therapeutic value. Because of their chemical complexity, therapeutic alkaloids are often obtained via plant-extraction. The microbial synthesis of alkaloids would allow for their rapid and scalable production; however, often times microbial production of a modified natural product can be more beneficial than production of the natural product itself. Here, an analysis was completed of current alkaloid-based pharmaceuticals to determine the steps necessary to engineer microbes to produce beneficial modified alkaloids. The yeast Saccharomyces cerevisiae was engineered to produce the modified monoterpene indole alkaloid (MIA) hydroxystrictosidine, which could enable the accelerated semisynthesis of anti-cancer pharmaceuticals. The work presented in this thesis represents the first production of a modified MIA in S. cerevisiae. This achievement involved the use of a pterin-dependent mono-oxidation strategy for the microbial synthesis of the biogenic amine serotonin and the leveraging of serotonin to produce hydroxystrictosidine. Subsequently, a
G-protein-coupled receptor-based sensor was developed to detect serotonin in the spent medium of a serotonin-producing microbe in a medium-throughput fashion in order to accelerate screening of improved serotonin producers, as an improved serotonin producer could then be converted into an improved modified MIA producer. Lastly, as compartmentalization of metabolic pathway enzymes can aid in improving production yields, the translocation efficiencies of multiple translocation tags were quantified to enable rational selection of translocation tags. Overall, this thesis presents the foundation for low-cost, renewable production of modified MIAs in the yeast S. cerevisiae.
Advisors/Committee Members: Peralta-Yahya, Pamela (advisor), Kelly, Wendy L. (committee member), Finn, M. G. (committee member), Williams, Loren (committee member), Storici, Francesca (committee member).
Subjects/Keywords: Yeast; Saccharomyces cerevisiae; Alkaloids; Monoterpene indole alkaloids; Synthetic biology; Compartmentalization; Tetrahydrobiopterin; Natural product biosynthesis; Hydroxystrictosidine; Serotonin; Metabolic engineering; GPCR; Biosensor
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APA (6th Edition):
Ehrenworth, A. M. (2017). Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60672
Chicago Manual of Style (16th Edition):
Ehrenworth, Amy M. “Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60672.
MLA Handbook (7th Edition):
Ehrenworth, Amy M. “Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae.” 2017. Web. 11 Apr 2021.
Vancouver:
Ehrenworth AM. Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60672.
Council of Science Editors:
Ehrenworth AM. Modified monoterpene indole alkaloid production in the yeast Saccharomyces cerevisiae. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60672
Georgia Tech
14.
Sago, Cory D.
Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech
URL: http://hdl.handle.net/1853/61737
► Genetic drugs (such as siRNAs, mRNAs, and CRISPR/Cas9) have the potential to be curative therapies for countless diseases. However, gene therapies will only work if…
(more)
▼ Genetic drugs (such as siRNAs, mRNAs, and CRISPR/Cas9) have the potential to be curative therapies for countless diseases. However, gene therapies will only work if the genetic drug is delivered to the diseased cell type. One promising delivery method is through the use of Lipid Nanoparticles (LNPs), due to their ease of manufacture and favorable toxicity profiles. Yet, LNPs have only seen clinical success as delivery methods to liver cells. In order to treat genetic diseases outside the liver, we hypothesized that a novel methodology for LNP discovery must be applied. Utilizing DNA barcodes to allow for the testing of >100 LNPs simultaneously, we determined that the correlation between LNP biodistribution in vitro and in vivo was negligible. Motivated by these results, we developed three novel technologies to increase the efficiency of LNP development for delivery of genetic therapies to non-liver cell types. The first technology (QUANT), allows the determination of absolute biodistribution of >150 LNPs simultaneously, we applied this to reveal the genetic mechanism by which liver endothelial and Kupffer cells uptake a majority of an injected LNP dose. The second and third technologies (FIND and siDown, respectively) enable the measurement of the cytosolic delivery of a mRNA or siRNA payload by >150 LNPs simultaneously. Using FIND, we developed a LNP that specifically delivers to splenic endothelial cells, enabling CRISPR-Cas9 mediated gene editing. Using siDown, we evolved a LNP with tropism to bone marrow endothelial cells. Lastly, we developed a novel oligonucleotide-based anti-CRISPR capable of enhancing the non-liver specificity of LNP-mediated CRISPR-Cas9 editing in wildtype animals. Cumulatively, we hope that this body of work helps LNPs deliver on their promise of enabling gene therapies to extra-hepatic tissues.
Advisors/Committee Members: Dahlman, James (advisor), Santangelo, Philip (advisor), Kwong, Gabe (committee member), Finn, M. G. (committee member), Roy, Krishnendu (committee member), Wilbur Lam (committee member).
Subjects/Keywords: Gene therapy; siRNA; Nanoparticles; mRNA; Gene editing; Cas9; DNA barcoding
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APA (6th Edition):
Sago, C. D. (2019). Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61737
Chicago Manual of Style (16th Edition):
Sago, Cory D. “Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61737.
MLA Handbook (7th Edition):
Sago, Cory D. “Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types.” 2019. Web. 11 Apr 2021.
Vancouver:
Sago CD. Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61737.
Council of Science Editors:
Sago CD. Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/61737
Georgia Tech
15.
Alonas, Eric James.
Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2015, Georgia Tech
URL: http://hdl.handle.net/1853/56173
► A method for labeling the genomic RNA of the human respiratory syncytial virus, as well as for isolating and examining the labeled filamentous virions was…
(more)
▼ A method for labeling the genomic RNA of the human respiratory syncytial virus, as well as for isolating and examining the labeled filamentous virions was achieved. This method utilized the multiply labeled tetravalent probe design, first described in Santangelo et al. 2009. It was shown that by introducing MTRIPs into RSV infected cells immediately before isolating virus, the genomic RNA within individual filamentous virions could be labeled and imaged. This process did not seem to decrease viral titer or affect viral morphology, and allowed for the imaging of the virus using fixed and live cell conventional fluorescence microscopy and super-resolution microscopic techniques such as dSTORM and STED. The imaging of other structural components of the virus, such as the
M protein, and as was discovered, the M2-1 protein was also shown. Additionally, the virus was examined for host proteins of the RLR family, which are involved in the cellular innate immune response. It was found that the protein MDA5 was localized in the isolated filaments. Finally, gold nanoclusters were covalently bound to the RNA probe to create a probe that would generate contrast in cryo-TEM and cryo-ET. By hybridizing the probe to an mRNA encoding GFP, complexing it with a cationic lipid transfection agent, and delivering it to cells before plunge-freezing, it was demonstrated that the mRNA-lipoplex granules could be detected. In conclusion, the method allows for both dynamic and ultrastructural information about the viral genome to be gathered.
Advisors/Committee Members: Santangelo, Philip J. (advisor), Barker, Thomas H. (committee member), Finn, M. G. (committee member), Wright, Elizabeth R. (committee member), Xi, Peng (committee member).
Subjects/Keywords: RSV; RNA imaging; Live cell imaging; dSTORM; STED; Cryo-ET; TEM; RNA virus; RNA probes
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APA (6th Edition):
Alonas, E. J. (2015). Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/56173
Chicago Manual of Style (16th Edition):
Alonas, Eric James. “Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/56173.
MLA Handbook (7th Edition):
Alonas, Eric James. “Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy.” 2015. Web. 11 Apr 2021.
Vancouver:
Alonas EJ. Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/56173.
Council of Science Editors:
Alonas EJ. Labeling the human respiratory syncytial virus genomic RNA with exogenous probes for fluorescence and electron microscopy. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/56173
Georgia Tech
16.
Fathi, Shaghayegh.
Targeted delivery of histone deacetylase inhibitors for use in cancer therapy.
Degree: PhD, Chemistry and Biochemistry, 2016, Georgia Tech
URL: http://hdl.handle.net/1853/61091
► Cancer is one of the leading causes of death around the world, with lung, breast and prostate cancer being the most common cancers. Most of…
(more)
▼ Cancer is one of the leading causes of death around the world, with lung, breast and prostate cancer being the most common cancers. Most of current cancer treatments are associated with various side effects such as depression, fatigue, hair loss, nausea, infection, fertility problems, anemia, and myelosuppression. Therefore, there is an unmet need to develop new and more potent anticancer therapeutic agents with less off-target toxicities. This thesis documents efforts at the design and synthesis of different classes of HDAC inhibitors (HDACi) as promising therapeutic agents in cancer therapy. These HDACi are anticpated to accumulate at the site of tumor due to selective tissue/cell distribution conferred on them by ligands, known to accumulate in certain tissues or target receptors that are overexpressed on tumor cells, incorporated into their the cap group. FDA approved macrolide, azithromycin, is known to accumulate in macrophage cells. Macrophage cells are known to have a high concentration in lung, hence, azithromycin has the potential to target and acuumulate in lung tissue. An unpublished in vivo data in our lab, showed that azithromycin maintains its lung accumulation after being modified and attached to HDACi moiety. Thus, we hypothesized conjugating the HDACi to azithromycin can lead to their delivery to lung tissues. To this end, in the second chapter, we designed and synthesized three different classes of azithromycin conjugated hydroxamic acid derived HDACi and evaluated their HDAC inhibitory potency and anti-proliferative activity in lung (A549) and breast (MCF-7) cancer cell lines.
It is believed that isoform selective HDACi may be endowed with less off-target toxicities and better therapeutic outcome and efficacy compared to pan HDACi which have no selectivity toward different HDAC isoforms. To evaluate this hypothesis, in the third chapter, we designed and synthesized isoform selective azithromycin conjugated HDACi, by replacing the hydroxamic acid zinc binding group with the N-(2-amino-5-(thiophen-2-yl)phenyl)acylamide zinc binding group which is a HDAC1 and HDAC2 selective. Additionally to determine these compounds ability to target lung tissue and protect it from metastasis, we tested the lead compound in a model of lung metastasis of breast cancer using spontaneous mouse mammary tumor model MMTV-PyMT-Tg. The in vivo study results showed that there was a greater tumor regression in mice that were treated with N-(2-amino-5-(thiophen-2-yl)phenyl)acylamide derived HDACi compared to hydroxamic acid derived HDACi. Additionally this class of HDACi was able to protect the lung tissue from metastasis better than its hydroxamic acid analogue. The fourth chapter focuses on continuation of prior SAR study on design multiple ligand compounds with selective estrogen receptor modular (SERM) and HDACi activities. In this study tamoxifen, an estrogen receptor (ER) antagonist, with a high binding affinity for ER, was used as the HDACi cap group. These antiestrogen equipped HDACi are expected to be better…
Advisors/Committee Members: Oyelere, Adegboyega Yomi (committee member), France, Stefan (committee member), Finn, M. G (committee member), Platt, Manu (committee member), Kubanek, Julia (committee member).
Subjects/Keywords: Cancer; Histone deacetylase; Histone deacetylase inhibitors; Targeted delivery; Azithromycin; Tamoxifen; SAHA; Pyrimethamine; Liposome
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APA (6th Edition):
Fathi, S. (2016). Targeted delivery of histone deacetylase inhibitors for use in cancer therapy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61091
Chicago Manual of Style (16th Edition):
Fathi, Shaghayegh. “Targeted delivery of histone deacetylase inhibitors for use in cancer therapy.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61091.
MLA Handbook (7th Edition):
Fathi, Shaghayegh. “Targeted delivery of histone deacetylase inhibitors for use in cancer therapy.” 2016. Web. 11 Apr 2021.
Vancouver:
Fathi S. Targeted delivery of histone deacetylase inhibitors for use in cancer therapy. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61091.
Council of Science Editors:
Fathi S. Targeted delivery of histone deacetylase inhibitors for use in cancer therapy. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/61091
17.
Geoghan, Allison F.
New chemical linkage systems to address biological problems.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61149
► The research reported in this thesis explored and developed the formation of reversible and irreversible chemical linkages for use in biological systems. Through the synthesis…
(more)
▼ The research reported in this thesis explored and developed the formation of reversible and irreversible chemical linkages for use in biological systems. Through the synthesis of a variety of peptides and small molecules, a new ligand system was developed to form covalent linkages through the Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Additionally, a class of ester-amide oxanorbornadiene (EA-OND) molecules was developed to release alcohol cargos by succinimide formation upon addition of a thiol reagent. The attachment and thiol-dependent release of cholesterol was characterized as an example of the manipulation of a drug-like cargo. Lastly, a new method for combating bacterial infections through the covalent attachment of antimicrobial small molecules to medical tubing via the CuAAC reaction was developed. These modifications minimized the number of viable bacteria attached to the surface of the material and were non-toxic to mammalian cells. Together, these projects expand the chemical toolbox for applying new technologies to biological systems.
Advisors/Committee Members: Finn, M. G. (advisor), Kubanek, Julia (committee member), France, Stefan (committee member), Reddi, Amit R. (committee member), Gaucher, Eric A. (committee member).
Subjects/Keywords: Click chemistry; CuAAC; Peptide; Linkers; Drug release; Antimicrobial; Surface modification; PVC; Medical tubing
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APA (6th Edition):
Geoghan, A. F. (2018). New chemical linkage systems to address biological problems. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61149
Chicago Manual of Style (16th Edition):
Geoghan, Allison F. “New chemical linkage systems to address biological problems.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61149.
MLA Handbook (7th Edition):
Geoghan, Allison F. “New chemical linkage systems to address biological problems.” 2018. Web. 11 Apr 2021.
Vancouver:
Geoghan AF. New chemical linkage systems to address biological problems. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61149.
Council of Science Editors:
Geoghan AF. New chemical linkage systems to address biological problems. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61149
Georgia Tech
18.
Rose, Harrison B.
Towards an enzymatic route to 2,5-furandicarboxylic acid.
Degree: PhD, Chemical and Biomolecular Engineering, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/61151
► This research project explored the selection and development of an enzymatic route from the renewable feedstocks furfural and carbon dioxide to 2,5-furandicarboxylic acid, a building…
(more)
▼ This research project explored the selection and development of an enzymatic route from the renewable feedstocks furfural and carbon dioxide to 2,5-furandicarboxylic acid, a building block for bio-based polyesters. A putative prenylated flavin-dependent reversible decarboxylase was identified as the most reasonable biocatalyst choice, although it was not isolated in a stable and active form in this work. To support future reaction engineering endeavors, this project also included studies of the aqueous liquid and solid solubility relationships between the reactive pathway intermediates and possible side products: furfural, 2 furancarboxylic acid, 5-formyl-2-furancarboxylic acid, and 2,5-furandicarboxylic acid. Finally, this work included an exploration into the mathematics of pH equilibria in aqueous reaction systems. These mathematical techniques were used to develop tools for assessing such systems by both colorimetric and calorimetric methods.
Advisors/Committee Members: Bommarius, Andreas S. (advisor), Realff, Matthew J. (committee member), Jones, Christopher W. (committee member), Finn, M. G. (committee member), Sadowski, Gabriele (committee member).
Subjects/Keywords: 2,5-furandicarboxylic acid; pH equilibria; Biocatalysis
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APA (6th Edition):
Rose, H. B. (2018). Towards an enzymatic route to 2,5-furandicarboxylic acid. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61151
Chicago Manual of Style (16th Edition):
Rose, Harrison B. “Towards an enzymatic route to 2,5-furandicarboxylic acid.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61151.
MLA Handbook (7th Edition):
Rose, Harrison B. “Towards an enzymatic route to 2,5-furandicarboxylic acid.” 2018. Web. 11 Apr 2021.
Vancouver:
Rose HB. Towards an enzymatic route to 2,5-furandicarboxylic acid. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61151.
Council of Science Editors:
Rose HB. Towards an enzymatic route to 2,5-furandicarboxylic acid. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61151
Georgia Tech
19.
DeLey Cox, Vanessa E.
Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/63483
► Non-canonical amino acid (ncAA) incorporation has led to significant advances in protein science and engineering. Traditionally, incorporation of ncAAs is achieved via amber codon suppression…
(more)
▼ Non-canonical amino acid (ncAA) incorporation has led to significant advances in protein science and engineering. Traditionally, incorporation of ncAAs is achieved via amber codon suppression using an engineered orthogonal aminoacyl-tRNA synthetase:tRNA pair. However, as more complex protein products are targeted, researchers are identifying additional barriers limiting the scope of currently available ncAA systems. One barrier is elongation factor Tu (EF-Tu), a protein responsible for proof-reading aa-tRNAs that substantially restricts ncAA scope by limiting ncaa-tRNA delivery to the ribosome. Researchers have responded by engineering ncAA-compatible EF-Tus for key ncAAs. However, this approach fails to address the extent to which EF-Tu inhibits efficient ncAA incorporation. Herein, we describe our efforts to transform how EF-Tu is utilized to incorporate ncAAs. Leveraging computational methods, we present data on four EF-Tu libraries and two tRNA libraries used in both in vitro and in vivo translation. Ultimately, the in vivo assay led to the identification of EF-Tu variants which accept non-native substrates. By mass spectrometry, we demonstrate two variants have expanded substrate acceptance. Fitness tests show a polyspecific EF-Tu is an accepted addition to the translation machinery and improves host organism fitness relative to an ncAA-specific engineered EF-Tu. These results lend credence to our choice of computational method (in this case REAP) and also suggest that EF-Tu and SelB may have a shared, substrate-promiscuous ancestor. Overall, we believe this approach complements current research highlighting the advantages of improved OTSs and promotes a more comprehensive approach critical to achieving future goals.
Advisors/Committee Members: Gaucher, Eric A. (advisor), Williams, Loren D. (advisor), Finn, M. G. (advisor), Oyelere, Adegboyega K. (committee member), Hud, Nicholas V. (committee member).
Subjects/Keywords: EF-Tu; Non-canonical amino acid; Orthogonal translation system; Genetic code expansion; Polyspecificity; Protein engineering; Ribosomal translation; Elongation factors
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APA (6th Edition):
DeLey Cox, V. E. (2018). Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63483
Chicago Manual of Style (16th Edition):
DeLey Cox, Vanessa E. “Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/63483.
MLA Handbook (7th Edition):
DeLey Cox, Vanessa E. “Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation.” 2018. Web. 11 Apr 2021.
Vancouver:
DeLey Cox VE. Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/63483.
Council of Science Editors:
DeLey Cox VE. Engineering elongation factor Tu and tRNAs to better accommodate non-canonical amino acids during translation. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/63483
Georgia Tech
20.
Buckley, Carolyn A.
Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors.
Degree: PhD, Chemistry and Biochemistry, 2019, Georgia Tech
URL: http://hdl.handle.net/1853/63515
► The molecular structures of polymeric semiconductors were strategically designed to impart electronic characteristics conducive to increasing electron-transport performance in organic field effect transistor devices. The…
(more)
▼ The molecular structures of polymeric semiconductors were strategically designed to impart electronic characteristics conducive to increasing electron-transport performance in organic field effect transistor devices. The polymers were synthesized by Stille polymerization, and optoelectronic properties of the materials investigated using spectroscopic and electrochemical analytical methods. The polymers were incorporated into transistor devices using blade-coating deposition methods, and the structures and topology of these thin films investigated using microscopy and X-ray spectroscopy techniques. Results indicated that the patterns of the orbital wavefunction distributions are as important in determining the final electronic properties of the polymers as the frontier energy levels of the component monomeric units in utilizing the ‘all-acceptor’ design strategy. The polymers synthesized successfully achieved electron-transport upon incorporation into field-effect transistor devices. The findings of this thesis suggest further refinement of common molecular semiconductor design strategies would benefit the development of high-performance polymeric semiconductors. Blade-coating processing studies on the development of polymeric nanofiber network formation within thin films and the impact on transistor performance are also examined. and the implications for further research are discussed.
Advisors/Committee Members: Reichmanis, Elsa (advisor), Finn, M. G. (committee member), Gutekunst, Will (committee member), Stingelin, Natalie (committee member), Collard, David (committee member).
Subjects/Keywords: Polymer; Semiconductor; Field-effect transistor
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APA (6th Edition):
Buckley, C. A. (2019). Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/63515
Chicago Manual of Style (16th Edition):
Buckley, Carolyn A. “Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/63515.
MLA Handbook (7th Edition):
Buckley, Carolyn A. “Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors.” 2019. Web. 11 Apr 2021.
Vancouver:
Buckley CA. Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/63515.
Council of Science Editors:
Buckley CA. Design and processing of charge transport polymer semiconductors and their applications in n-channel organic field effect transistors. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/63515
Georgia Tech
21.
Blanchard, Emmeline LeGendre.
Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2019, Georgia Tech
URL: http://hdl.handle.net/1853/64033
► The molecular machinery of the cell is governed by interactions between proteins, DNA, and RNA. For example, innate immune system activation is characterized by the…
(more)
▼ The molecular machinery of the cell is governed by interactions between proteins, DNA, and RNA. For example, innate immune system activation is characterized by the formation and disassociation of protein complexes in a signaling cascade. Alternatively, protein interactions with mRNA control the transcription, transport, and stability of mRNA. Resultingly, abnormal interactions disrupt function, contributing to tumorigenesis. Similarly, protein-protein and protein-RNA interactions in the ribonucleocapsid complex of respiratory syncytial virus govern transcription and replication of the virus.
To gain a better understanding of these interactions, a thorough investigation is required in cells and tissue samples. Conventionally used tools to study interactions are often limited in their specificity and sensitivity. The overall goal of the work presented here was to demonstrate and develop a toolbox to quantify and localize protein-protein and RNA-protein interactions in fixed cells and tissues, and to use these tools to gain insight into the role of molecular interactions in several applications. First, we demonstrated the utility of proximity ligation assays to measure innate immune system activation in both cells and tissue. Next, we developed a methodology of measuring mRNA-protein interactions in archival, patient-derived tissue, specifically examining abnormal mRNA-protein interactions in cancer. Finally, we used proximity ligation assays and our developed methodology to investigate the role of the respiratory syncytial virus ribonucleocapsid complex in the transcription/replication switch in infection. We believe these methods are easy to use and highly translatable to new applications, and therefore of great interest to research where molecular interactions are of importance.
Advisors/Committee Members: Santangelo, Philip J. (advisor), Bassell, Gary (committee member), Dreaden, Erik (committee member), Finn, M. G. (committee member), Roy, Krishnendu (committee member).
Subjects/Keywords: Proximity ligation assays; innate immune system; post-transcriptional regulation; cancer; respiratory syncytial virus
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APA (6th Edition):
Blanchard, E. L. (2019). Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/64033
Chicago Manual of Style (16th Edition):
Blanchard, Emmeline LeGendre. “Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/64033.
MLA Handbook (7th Edition):
Blanchard, Emmeline LeGendre. “Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue.” 2019. Web. 11 Apr 2021.
Vancouver:
Blanchard EL. Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/64033.
Council of Science Editors:
Blanchard EL. Characterizing protein-protein and RNA-protein interactions in fixed cells and tissue. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/64033
22.
Beveridge, Jennifer Marie.
Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates.
Degree: MS, Chemistry and Biochemistry, 2015, Georgia Tech
URL: http://hdl.handle.net/1853/53594
► The bioorthogonal copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction exhibits complex but well-defined kinetics in aqueous and organic solution for soluble azides, alkynes, and ligand-bound copper(I). The…
(more)
▼ The bioorthogonal copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction exhibits complex but well-defined kinetics in aqueous and organic solution for soluble azides, alkynes, and ligand-bound copper(I). The kinetic profile in two dimensions, however, for CuAAC systems within a lipid bilayer membrane, has yet to be defined. The effect of triazole formation with lipid membrane-bound components on membrane properties such as fluidity and permeability is also of interest. Azide- and alkyne-functionalized lysolipids were synthesized and incorporated into non-fluid vesicles, which were then subject to CuAAC. The rate order for membrane-bound lipid substrates in non-fluid vesicles was observed to be comperable to that of the reaction in solution. Reactions between vesicles showed evidence of lipid transfer between non-fluid membranes, which has not been previously reported. For intervesicular and intravesicular reactions in non-fluid membranes, the observed reactivity was found to be opposite that of previously published reactions between nucleophiles and electrophiles in fluid lipid systems. Applications of this work include the potential for novel symmetric membrane leaflet labeling, bioorthogonal manipulation of cell and tissue function, and the creation of membranes with precisely controlled properties that may not be available in naturally-occurring membranes.
Advisors/Committee Members: Finn, M. G. (advisor), Merrill, Alfred (committee member), Hud, Nicholas (committee member).
Subjects/Keywords: Click chemistry; Bioorthogonal; Lipid membranes
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APA (6th Edition):
Beveridge, J. M. (2015). Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53594
Chicago Manual of Style (16th Edition):
Beveridge, Jennifer Marie. “Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates.” 2015. Masters Thesis, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/53594.
MLA Handbook (7th Edition):
Beveridge, Jennifer Marie. “Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates.” 2015. Web. 11 Apr 2021.
Vancouver:
Beveridge JM. Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates. [Internet] [Masters thesis]. Georgia Tech; 2015. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/53594.
Council of Science Editors:
Beveridge JM. Copper(I)-catalyzed azide-alkyne cycloaddition with membrane bound lipid substrates. [Masters Thesis]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/53594
23.
Lloyd, Jessica.
Development of biocompatible dextran-oxanorbornadiene hydrogels.
Degree: MS, Chemistry and Biochemistry, 2019, Georgia Tech
URL: http://hdl.handle.net/1853/61784
► Hydrogels have garnered much attention over the past few decades for their ability to deliver therapeutics with spatial and temporal control. However, many of these…
(more)
▼ Hydrogels have garnered much attention over the past few decades for their ability to deliver therapeutics with spatial and temporal control. However, many of these systems can exhibit burst release and are not easily adjusted to realize different release kinetics. The research reported in this thesis aims to develop tunable degradable hydrogels from oxanorbornadiene linkers, which have been shown to have programmable fragmentation rates that can be tuned over an exceptionally wide range of time. OND hydrogels of different crosslinking compositions were all able to form robust gels in as little as seconds and release of entrained cargo was found to be tunable over 0.5 to 25 days by changing the OND substitution or crosslinking system. Oxanorbornadiene hydrogels were then applied to in vivo models seeking to improve healing in chronic wounds where it was found that OND hydrogels were able to deliver therapeutic cargo at the expected preprogrammed rates to improve wound healing. Degradable hydrogels comprised of OND cleavable linkages continue to show great promise as simple drug delivery systems that can be widely useful to applications requiring controlled release over hours or months.
Advisors/Committee Members: Finn, M. G. (advisor), Gutekunst, Will (committee member), Reddi, Amit (committee member).
Subjects/Keywords: Degradable hydrogels; Drug delivery
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APA (6th Edition):
Lloyd, J. (2019). Development of biocompatible dextran-oxanorbornadiene hydrogels. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61784
Chicago Manual of Style (16th Edition):
Lloyd, Jessica. “Development of biocompatible dextran-oxanorbornadiene hydrogels.” 2019. Masters Thesis, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61784.
MLA Handbook (7th Edition):
Lloyd, Jessica. “Development of biocompatible dextran-oxanorbornadiene hydrogels.” 2019. Web. 11 Apr 2021.
Vancouver:
Lloyd J. Development of biocompatible dextran-oxanorbornadiene hydrogels. [Internet] [Masters thesis]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61784.
Council of Science Editors:
Lloyd J. Development of biocompatible dextran-oxanorbornadiene hydrogels. [Masters Thesis]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/61784
Georgia Tech
24.
Sandridge, Matthew J.
Dehydrative cyclizations via acid catalysis as a method for molecular diversity.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/59880
► Development of new synthetic methodologies that allow for efficient access to desirable core structures is a consistently valuable area of research for synthetic chemistry. Good…
(more)
▼ Development of new synthetic methodologies that allow for efficient access to desirable core structures is a consistently valuable area of research for synthetic chemistry. Good methodologies provide rapid access to systematically varying compounds with desirable properties, enabling functional testing and the discovery of new, useful compounds and materials. Three novel synthetic methodologies that make use of dehydrative cyclizations of carbinols via Lewis acid catalysis have been developed towards this end: (1) A calcium-catalyzed, dehydrative, ring-opening cyclization of cyclopropyl carbinols to form (hetero)aryl-fused cyclohexa-1,3-dienes; (2) A Bi(OTf)3-catalyzed synthesis of α-alkylidene-γ-butyrolactones from the ring-opening cyclization of cyclopropyl carbinols; (3) A calcium-catalyzed synthesis of cyclopenta[b]thiophenes and indenes via dehydrative Nazarov-type electrocyclizations of alkenyl (hetero)aryl carbinols. The mechanistic details of how each of these methods perform have also been investigated. Initial results and proposals for consequent projects, which span the breadth of target synthesis and new methodologies, have also been established.
Advisors/Committee Members: France, Stefan (advisor), Collard, David (committee member), Bommarius, Andreas (committee member), Finn, M. G. (committee member), Payne, Christine (committee member), Gutekunst, William (committee member).
Subjects/Keywords: Acid catalysis; Molecular diversity; Dehydrative cyclizations; Organic synthesis
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APA (6th Edition):
Sandridge, M. J. (2018). Dehydrative cyclizations via acid catalysis as a method for molecular diversity. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59880
Chicago Manual of Style (16th Edition):
Sandridge, Matthew J. “Dehydrative cyclizations via acid catalysis as a method for molecular diversity.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/59880.
MLA Handbook (7th Edition):
Sandridge, Matthew J. “Dehydrative cyclizations via acid catalysis as a method for molecular diversity.” 2018. Web. 11 Apr 2021.
Vancouver:
Sandridge MJ. Dehydrative cyclizations via acid catalysis as a method for molecular diversity. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/59880.
Council of Science Editors:
Sandridge MJ. Dehydrative cyclizations via acid catalysis as a method for molecular diversity. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/59880
Georgia Tech
25.
Jue, Melinda L.
PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis.
Degree: PhD, Chemical and Biomolecular Engineering, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/60699
► Current separation technologies rely heavily on energy-intensive methods such as distillation, crystallization, and absorption to separate organic molecules. Utilization of membrane-based organic solvent separations—that avoid…
(more)
▼ Current separation technologies rely heavily on energy-intensive methods such as distillation, crystallization, and absorption to separate organic molecules. Utilization of membrane-based organic solvent separations—that avoid phase changes during separation—could revolutionize the field by enabling new low energy, low carbon emission technologies. However, existing membrane materials are unable to achieve the separation efficiency required to differentiate between very similarly sized organic molecules. Microporous materials are potential game changers in this area due to their ability to provide superb size and shape discrimination. Polymers of intrinsic microporosity (PIMs) are an emerging subclass of materials with rigid backbones that lead to high membrane performance combined with solution processability. To bridge the gap between the development of new, high performance polymers and industrially attractive technologies, more efficient membrane units such as hollow fibers are needed. This work describes the organic solvent molecule transport in and the fabrication of defect-free, asymmetric hollow fiber membranes from PIM-1. These membranes are then used as precursors for the development and proof-of-concept demonstration of microporous carbon molecular sieve membranes for the molecular differentiation of organic solvent molecules. The work here spans a wide range of membrane science and engineering from polymer synthesis, membrane fabrication, and fundamental transport analysis to module formation and testing.
Advisors/Committee Members: Lively, Ryan P. (committee member), Breedveld, Victor (committee member), Finn, M. G. (committee member), Koros, William J. (committee member), Ludovice, Peter J. (committee member), McCool, Benjamin A. (committee member).
Subjects/Keywords: Membranes; Polymers of intrinsic microporosity; Carbon molecular sieves; Organic solvent separations
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APA (6th Edition):
Jue, M. L. (2017). PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60699
Chicago Manual of Style (16th Edition):
Jue, Melinda L. “PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60699.
MLA Handbook (7th Edition):
Jue, Melinda L. “PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis.” 2017. Web. 11 Apr 2021.
Vancouver:
Jue ML. PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60699.
Council of Science Editors:
Jue ML. PIM-1-derived carbon molecular sieve hollow fiber membranes for organic solvent reverse osmosis. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/60699
26.
Smeekens, Johanna.
Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins.
Degree: PhD, Chemistry and Biochemistry, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/58297
► Extracellular glycoproteins are extremely important to a variety of biological processes, including immune response, cell interactions and disease development. Despite their critical importance, glycoproteins are…
(more)
▼ Extracellular glycoproteins are extremely important to a variety of biological processes, including immune response, cell interactions and disease development. Despite their critical importance, glycoproteins are challenging to analyze due to their low abundance and heterogeneity of glycans. The work in this dissertation focuses on the development of mass spectrometry-based methods to globally analyze cell surface and secreted glycoproteins. First, a novel method was developed for site-specific identification of the cell surface N-glycoproteome in HEK 293T cells. This method was applied to investigate cell surface glycoprotein changes in MCF 10A cells undergoing the epithelial-mesenchymal transition. Next, secreted proteins and glycoproteins were comprehensively analyzed from Saccharomyces cerevisiae, which is an excellent model system for eukaryotic cells. Finally, an enhanced digestion method for improved membrane protein identification by MS was developed for applications with membrane glycoprotein analysis. Altogether, this work affords new opportunities and methods for large-scale analysis of extracellular glycoproteins, which can be extensively applied to further decode the extracellular glycoproteome.
Advisors/Committee Members: Wu, Ronghu (advisor), Fernandez, Facundo (committee member), Finn, M. G. (committee member), Kemp, Melissa (committee member), Williams, Loren (committee member).
Subjects/Keywords: Glycosylation; Proteomics; Mass spectrometry; Cell surface; Secretome
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APA (6th Edition):
Smeekens, J. (2017). Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58297
Chicago Manual of Style (16th Edition):
Smeekens, Johanna. “Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/58297.
MLA Handbook (7th Edition):
Smeekens, Johanna. “Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins.” 2017. Web. 11 Apr 2021.
Vancouver:
Smeekens J. Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/58297.
Council of Science Editors:
Smeekens J. Novel mass spectrometry-based methods to identify and quantify extracellular glycoproteins. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58297
27.
Geng, Zhishuai.
Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function.
Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech
URL: http://hdl.handle.net/1853/60227
► The goal of the research reported in this thesis is to investigate reversible bond formation in bicyclo[3.3.1] system through anchimeric assistance and use that as…
(more)
▼ The goal of the research reported in this thesis is to investigate reversible bond formation in bicyclo[3.3.1] system through anchimeric assistance and use that as building blocks to assemble functional cationic materials, with both low and high molecular weights, linear and hyperbranched architecture. The degradability/fragmentability of the resulting materials could be easily tuned based on physical organic fundamental principles. The application of them in gene delivery demonstrated comparable efficiency to commercial available standards. The materials also demonstrated desired broad spectrum antimicrobial activity with less likelihood of resistance development and potential to be used as antimicrobial coating. With more optimization, this new type of cationic material is promising to achieve goals traditional polycation could not.
Advisors/Committee Members: France, Stefan (advisor), Finn, M. G. (committee member), Marder, Seth (committee member), Reynolds, John (committee member), Curtis, Jennifer (committee member).
Subjects/Keywords: Fragmentable polycation; Antimicrobial; Transfection; Bicyclononane.
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APA (6th Edition):
Geng, Z. (2018). Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/60227
Chicago Manual of Style (16th Edition):
Geng, Zhishuai. “Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/60227.
MLA Handbook (7th Edition):
Geng, Zhishuai. “Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function.” 2018. Web. 11 Apr 2021.
Vancouver:
Geng Z. Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/60227.
Council of Science Editors:
Geng Z. Fragmentable bicyclo[3.3.1]nonane cationic materials and their applications to nucleic acid delivery and antimicrobial function. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/60227
28.
Varner, Chad.
Developing synthetic multivalent cellular effectors.
Degree: PhD, Chemical and Biomolecular Engineering, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/58743
► I have designed bioconjugates that can elicit desired cellular responses – cellular effectors. Using multivalent interactions, involving the simultaneous binding of multiple receptors to multiple…
(more)
▼ I have designed bioconjugates that can elicit desired cellular responses – cellular effectors. Using multivalent interactions, involving the simultaneous binding of multiple receptors to multiple ligands, I have designed cellular effectors to use as vaccines and to direct stem cell fate. I have developed multivalent scaffolds to be used as a “universal” influenza vaccine, vaccine constructs for Respiratory Syncytial Virus (RSV) that do not present the variable antigenic site Ø, developed a novel strategy for nanopatterning protein antigens to guide the immune response toward and away from desired epitopes, and generated polypeptide-based scaffolds that can explicitly control the valency of multivalent conjugates as well as the inter-ligand spacing and used these to direct stem cell fate. All of these systems have shown that by controlling the nanoscale presentation of ligands, the system response can be altered and directed toward a desired behavior. The scaffolds that I have developed can be used in other vaccine design and stem cell proliferation studies. The general application of nanopatterning protein antigens has already been applied to several other systems in our lab and we hypothesize that it will be broadly applicable in future antigen design studies. Thus, the work presented in this thesis will stand as a foundation for future studies in vaccine design and cell signaling studies.
Advisors/Committee Members: Kane, Ravi (advisor), Finn, M. G. (committee member), Roy, Krish (committee member), Lu, Hang (committee member), Prausnitz, Mark (committee member).
Subjects/Keywords: Multivalency; Vaccines; Effectors
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APA (6th Edition):
Varner, C. (2017). Developing synthetic multivalent cellular effectors. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58743
Chicago Manual of Style (16th Edition):
Varner, Chad. “Developing synthetic multivalent cellular effectors.” 2017. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/58743.
MLA Handbook (7th Edition):
Varner, Chad. “Developing synthetic multivalent cellular effectors.” 2017. Web. 11 Apr 2021.
Vancouver:
Varner C. Developing synthetic multivalent cellular effectors. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/58743.
Council of Science Editors:
Varner C. Developing synthetic multivalent cellular effectors. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58743
29.
Ligon, Evelyn.
Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets.
Degree: PhD, Chemistry and Biochemistry, 2019, Georgia Tech
URL: http://hdl.handle.net/1853/61271
► Methodology development is an essential pursuit to enable the synthesis of pharmaceutically-relevant targets. The emergent concept of privileged scaffolds has provided a framework for focused…
(more)
▼ Methodology development is an essential pursuit to enable the synthesis of pharmaceutically-relevant targets. The emergent concept of privileged scaffolds has provided a framework for focused synthetic methodology development toward polycyclic heteroaromatic compounds with inherent and important bioactivities. This thesis explores novel applications of the Friedel-Crafts reaction toward three medicinal compounds and their privileged scaffolds: flubromazepam, a 1,4-benzodiazepine; tronocarpine, a tetrahydro-7,11-methanoazocino[1,2-a]indole; and rhazinicine, a tetrahydroindolizine. Several 1,4-benzodiazepine positional isomers were synthesized and characterized for the first time. Additionally, significant advances in knowledge were accomplished toward the reactivity and stereochemical behavior of donor-acceptor bicyclo[3.1.0]hexanes, an understudied class of DACPs, in intramolecular ring-opening cyclizations, and a novel formal [3+2] cycloaddition of a C5-substituted D-A oxabicyclo[3.1.0]hexane was demonstrated.
Advisors/Committee Members: France, Stefan (advisor), Finn, M. G. (committee member), Collard, David (committee member), Sadighi, Joseph (committee member), Blakey, Simon (committee member).
Subjects/Keywords: Friedel-Crafts; Privileged scaffolds; Benzodiazepine; Donor-acceptor cyclopropane; Bicyclo[3.1.0]hexane
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APA (6th Edition):
Ligon, E. (2019). Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61271
Chicago Manual of Style (16th Edition):
Ligon, Evelyn. “Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets.” 2019. Doctoral Dissertation, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/61271.
MLA Handbook (7th Edition):
Ligon, Evelyn. “Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets.” 2019. Web. 11 Apr 2021.
Vancouver:
Ligon E. Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets. [Internet] [Doctoral dissertation]. Georgia Tech; 2019. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/61271.
Council of Science Editors:
Ligon E. Testing the boundaries of novel Friedel-Crafts-type methodologies inspired by n-heteroaromatic medicinal targets. [Doctoral Dissertation]. Georgia Tech; 2019. Available from: http://hdl.handle.net/1853/61271
30.
Levinson, Nathanael Simeon.
Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen.
Degree: MS, Chemistry and Biochemistry, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/58251
► Antibiotic resistance is increasingly a health and financial burden on the global population. Use and misuse of antibiotics has led to increased frequencies of antibiotic-resistant…
(more)
▼ Antibiotic resistance is increasingly a health and financial burden on the global population. Use and misuse of antibiotics has led to increased frequencies of antibiotic-resistant infections worldwide, leading to fatalities as well as greatly increasing healthcare costs. To combat this, researchers have done much work to expand to the field of antibiotics, delving back into old compounds and testing massive libraries of compounds with rapid screening techniques. Tamoxifen is one such compound that is primarily used as an anticancer agent, but displays many useful other characteristic, including antibacterial effects. However, the mechanism of the antibacterial effects of tamoxifen are poorly documented. My research was aimed at both improving the effectivity of tamoxifen as an antibacterial and elucidating the mechanism of action of tamoxifen.
Advisors/Committee Members: Finn, M. G. (advisor), Oyelere, Yomi (committee member), Lieberman, Raquel (committee member), France, Stefan (committee member), DiChristina, Thomas (committee member).
Subjects/Keywords: Antibiotics; Tamoxifen
Record Details
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Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Levinson, N. S. (2017). Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/58251
Chicago Manual of Style (16th Edition):
Levinson, Nathanael Simeon. “Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen.” 2017. Masters Thesis, Georgia Tech. Accessed April 11, 2021.
http://hdl.handle.net/1853/58251.
MLA Handbook (7th Edition):
Levinson, Nathanael Simeon. “Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen.” 2017. Web. 11 Apr 2021.
Vancouver:
Levinson NS. Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen. [Internet] [Masters thesis]. Georgia Tech; 2017. [cited 2021 Apr 11].
Available from: http://hdl.handle.net/1853/58251.
Council of Science Editors:
Levinson NS. Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen. [Masters Thesis]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/58251
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