Department of Chemistry and Biochemistryhttp://hdl.handle.net/10106/94672024-03-29T02:26:42Z2024-03-29T02:26:42ZLong non-coding RNAs in inflammation, macrophage activation, and inflammatory human diseaseshttp://hdl.handle.net/10106/318022023-11-09T22:34:29Z2023-08-28T00:00:00ZLong non-coding RNAs in inflammation, macrophage activation, and inflammatory human diseases
**Please note that the full text is embargoed until 08/01/2025** Inflammation and immune signaling is central to infection and diseases. Growing evidence suggests that along with protein coding genes, long non-coding RNAs (lncRNAs) play a critical role in disease onset, combat, and recovery against pathogen, damaged and self-altered cells. Our lab has been extensively studying the role of lncRNA HOTAIR (HOX transcript antisense intergenic RNA) in gene regulation and epigenetics, and eventually discovered its hidden function regulating inflammation and immune signaling in macrophage, a major type of cell involved in immunity. Previous scholars in our lab have successfully demonstrated lncRNA HOTAIR’s regulatory molecular mechanism elucidating its specific role in cellular process. That paved the path to look for novel regulators of inflammation and immune signaling in human. Since the entire work was previously done on mouse model, and the major challenge working with mouse model was, unlike protein coding genes, lncRNAs are often found not conserved from species to species. Therefore, to find out novel players in inflammation and immune diseases, I focused on the human system.
The Chapter 1 gives an overview of immunity, immune system, and macrophage, a brief discussion on major inflammation regulatory signaling pathways like NF-κB (Nuclear factor-κB), MAP kinase (Mitogen‑activated protein kinase), and JAK-STAT (Janus kinase-signal transducers and activators of transcription) signaling pathways. An extensive discussion and literature review is summarized on reported lncRNAs linked to inflammation and immune signaling.
To achieve the first step of my goal, I showcased my work on human monocyte derived macrophage stimulated with inflammatory stimuli, LPS (lipopolysaccharide, bacterial endotoxin),
a gram-negative bacterial cell wall component. To find out the novel lncRNAs, I unbiasedly stimulated macrophage and performed an RNA-sequencing (RNA-seq). The RNA-seq revealed a series of uncharacterized novel lncRNAs. We named this class of lncRNAs as human Long noncoding inflammation associated RNAs (hLinfRNAs). In Chapter 2, I focused on studying the top expressing lncRNA, uncovered its function as a regulator of cytokine expression.
The Chapter 3 is focused on characterizing an another lncRNA, hLinfRNA3, which was found to be regulated by JAK-STAT signaling pathway despite of being induced by LPS (an NF-κB signaling pathway stimulant). Knockdown study indicating its function in regulating STAT3 response gene, like SOCS3 (suppressor of cytokine signaling 3), suggesting its potential involvement in JAK-STAT signaling pathway.
In Chapter 4, I extended my study into inflammatory disease model such as Alzheimer's disease (AD), majorly caused by accumulation of amyloid-beta (Aβ-peptide) peptide plaque in AD patients’ brain. Both in vitro and in vivo study in mice and rat showed that lncRNA HOTAIR is involved in Aβ mediated neuroinflammation, and its potential role in disease progression. The hLinfRNAs are also found upregulated in Aβ stimulated human microglia cells, suggesting their potential involvement in neuroinflammation.
Overall, my research has discovered novel players of inflammation and immune signaling in human. This may provide a more in-depth scientific understanding and may offer novel diagnostic and therapeutic approaches.
2023-08-28T00:00:00ZBAND GAP ENGINEERING IN TERNARY OXIDES AND SULFIDES: A ROUTE TO NEW PHOTOELECTRODES FOR SOLAR ENERGY CONVERSIONhttp://hdl.handle.net/10106/317952023-11-09T22:35:49Z2023-08-23T00:00:00ZBAND GAP ENGINEERING IN TERNARY OXIDES AND SULFIDES: A ROUTE TO NEW PHOTOELECTRODES FOR SOLAR ENERGY CONVERSION
**Please note that the full text is embargoed until 08/01/2024** In recent years, there has been a growing interest in semiconductor photoelectrodes that can effectively split water into hydrogen and oxygen using sunlight. However, there is currently no known material that is efficient enough to be used for commercial purposes. Photoelectrodes currently have an efficiency of less than 10% in converting water under visible light irradiation. There is a need to develop an efficient semiconductor photoelectrode for photoelectrochemical water splitting that is both chemically stable and affordable, composed of earth-abundant elements and capable of operating under visible light. Metal oxides are considered promising photoelectrode materials due to their low cost, stability against oxidation, and tunable band gaps. This study aims to expand the library of metal oxide and sulfide materials that could potentially be used as photoelectrode materials for photoelectrochemical (PEC) water splitting.
This research briefly introduces the photoelectrochemical technique and reviews various methods to tune the optoelectronic properties of semiconductors for solar fuel generation, focusing on improving the performance of visible-light active PEC materials. Through a combination of theory and experimentation, the potential of ternary metal oxide semiconductors in the A-Cu-V-O family (A= alkaline earth metal) was evaluated for PEC water splitting. By successfully incorporating 10% alkaline earth metals into α-CuV2O6, the optical band gap and PEC activity could be fine-tuned.
Finally, we successfully synthesized alkaline earth metal vanadates, namely Mg2V2O7, Ca2V2O7, and Sr2V2O7, as well as quaternary vanadates of copper and alkaline earth metals through a solution combustion synthesis method that is both time- and energy-efficient. These metal oxide semiconductors have the potential as photoelectrode materials for PEC water splitting. We used both theory and experiment to investigate the effect of alkaline earth metal substitution on the crystal structure, optoelectronic properties, and PEC properties of copper pyrovanadate. Additionally, we were able to synthesize two polymorphs of ternary praseodymium sulfide, cubic NaPrS2 (C) and rhombohedral NaPrS2 (R), via the solid-state method. Notably, we successfully produced the layered R-NaPrS2 for the first time through slow cooling to room temperature.
2023-08-23T00:00:00ZIdentification of acidic residues in proteins by selective chemical labeling and tandem mass spectrometryhttp://hdl.handle.net/10106/317892023-11-09T22:37:12Z2023-08-15T00:00:00ZIdentification of acidic residues in proteins by selective chemical labeling and tandem mass spectrometry
**Please note that the full text is embargoed until 08/01/2025** Proteins play important role in carrying out a wide range of cellular activities. They are subjected to various post-translational modifications (PTMs) by the addition of functional groups such as acetyl, phosphoryl, and methyl which leads to changes in their biological functions, localization, activity, and structure. The growth of MS technology has immensely facilitated the identification of PTMs comprehensively. This dissertation focuses on mapping these changes using covalent labeling techniques by tagging carboxylic acid residues, which undergo various kinds of PTMs. The second chapter focuses on the methods designed for Affinity Purification Mass Spectrometry (AP-MS) chemical cross-linking (CXL) of protein complexes.
There are numerous methods available for bioconjugation which target cysteine, lysine, and arginine residues. Although carboxyl residues, which are prevalent in proteins, are essential for preserving the protein's functionality, there are currently few accessible selective labeling procedures. We have described a novel reactive probe that allows for the chemoselective modification of acidic residues in peptides and proteins. We evaluated the reactivity of diphenyldiazomethane (DPDAM) in peptides and proteins in the third chapter. The fragmentation patterns of these labeled peptides have been investigated using tandem mass spectrometry.
2023-08-15T00:00:00ZReactive Atmosphere Pyrolysis(RAP) of Silicon Carbo Nitride (SiCN)http://hdl.handle.net/10106/317352023-11-09T22:48:53Z2023-08-17T00:00:00ZReactive Atmosphere Pyrolysis(RAP) of Silicon Carbo Nitride (SiCN)
Polymer Derived Ceramics (PDCs) are synthesized by converting liquid polymer precursors into ceramics through controlled pyrolysis. This study focuses on silicon carbonitride (SiCN) ceramics obtained from Ceraset Polysilazane (Durazane1800) precursor. The influence of pyrolysis atmospheres, including inert (Ar, N2) and reactive (H2) environments, on the thermal conversion of Durazane1800 into SiCN ceramics is investigated. The resulting ceramics' chemical variations are explored through phase analysis using X-ray diffraction (XRD), Raman spectroscopy, and thermogravimetric analysis (TGA). Notably, the impact of hydrogen versus nitrogen atmospheres on the conversion process is analyzed, shedding light on their distinct contributions to the composition and properties of SiCN ceramics. The findings contribute to a comprehensive understanding of PDC synthesis, offering insights into tailoring ceramics for diverse applications.
2023-08-17T00:00:00Z