You searched for +publisher:"Rutgers University" +contributor:("Kwan, Kelvin").
Showing records 1 – 7 of
7 total matches.
No search limiters apply to these results.
Rutgers University
1.
Patel, Sahishnu V., 1988-.
NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.
Degree: PhD, Chemistry and Chemical Biology, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/ 
► Stem cell engineering for regenerative medicine offers new hope for treating many ailments and injuries. Hence, there is an urgent demand by stem cell scientists…
(more)
▼ Stem cell engineering for regenerative medicine offers new hope for treating many ailments and injuries. Hence, there is an urgent demand by stem cell scientists for an alternative platform that induces stem cell differentiation in a safe and efficient manner. Stem cell differentiation is inherently regulated by transcription factors (TFs), which are multi-domain proteins that interact with DNA to control expression of target genes, and thus, TFs are master regulators of gene expression and cellular behavior. Recently, scientists have developed synthetic transcription factors (STFs), which are small molecules that mimic the function of the individual domains on TF proteins. This work presents the development a novel bio-inspired platform called NanoScript, which is an alternative approach for safe stem cell differentiation. NanoScript is a nanoparticle-based artificial TF protein because it is designed to replicate the function and structure of natural TF proteins. NanoScript was constructed by assembling STFs onto multifunctional nanoparticles. We first demonstrate that NanoScript localizes within the nucleus of cells, initiates transcription of a reporter plasmid by over 15-fold in cancer cells, and transcribes endogenous genes. The tunable and interchangeable components of NanoScript can easily be modified to either activate or deactivate any gene of interest. As a result, NanoScript was then demonstrated for three stem cell-based applications: 1) NanoScript targets myogenic genes to differentiate adipose-derived mesenchymal stem cells (ADMSCs) into muscle cells, 2) NanoScript modified with an epigenetic modulator, CTB, increases transcriptional potency and enhances differentiation of ADMACs into chondrocytes, and 3) NanoScript redesigned with gene repression molecules acts a transcriptional repressor protein because it downregulates gene expression to induce differentiation of neural stem cells into functional neurons. Because of its robust tunability and biocompatibility, the patented NanoScript platform is a promising alternative tool for research scientists for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Moreover, the ability of NanoScript to induce stem cell differentiation in a non-viral and footprint-free manner is highly desired by stem cell clinicians, and hence, holds potential for use in stem cell-based therapies.
Advisors/Committee Members: Lee, KiBum (chair), Brennan, John (internal member), Li, Jing (internal member), Kwan, Kelvin (outside member).
Subjects/Keywords: Nanoparticles; Stem cells; Transcription factors
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Patel, Sahishnu V., 1. (2015). NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48620/
Chicago Manual of Style (16th Edition):
Patel, Sahishnu V., 1988-. “NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.” 2015. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/48620/.
MLA Handbook (7th Edition):
Patel, Sahishnu V., 1988-. “NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.” 2015. Web. 05 Mar 2021.
Vancouver:
Patel, Sahishnu V. 1. NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/.
Council of Science Editors:
Patel, Sahishnu V. 1. NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/
Rutgers University
2.
Christensen, Chase Tyler, 1992-.
Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer.
Degree: MS, Curcumin, 2020, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/64051/
► A cancer diagnosis is an event that countless people fear. Besides the debilitating effects of the disease itself, treatments also take a substantial toll on…
(more)
▼ A cancer diagnosis is an event that countless people fear. Besides the debilitating effects of the disease itself, treatments also take a substantial toll on a patient’s health as well as their finances. Even successful treatments cause survivors to live with the constant concern that their illness will return. When relapse does occur, prior therapies may no longer be an option due to cancer cells gaining resistance under the cancer stem cell model. As such, new therapies must be developed to once again aid patients enter a second battle for their lives.
Phytochemicals, for example curcumin, are plant derived molecules that have shown promise as a potential treatment for ovarian and other cancers. In addition to phytochemicals, repurposed FDA approved drugs are another option being explored by researchers. Studying drugs that are already approved for other indications will reduce the time and cost required to develop new therapies. For people living with limited access to medical care due to financial matters, low cost treatment for deadly diseases is highly desired.
By conducting a series of in vitro alamarBlue cell viability assays, this paper aims to provide evidence that niclosamide, an off patent FDA approved drug for parasitic tapeworm infection, and curcumin, a phytochemical derived from turmeric, hold the potential to be low cost therapies for women suffering from ovarian cancer. In addition, using these molecules in combination has shown synergistic properties that act to decrease cell viability of SKOV3 ovarian cancer cells. Under the cancer stem cell model, cases of relapse may be reduced by using niclosamide and curcumin to target resistant subpopulations of cancer cells left after conventional therapies are administered.
Advisors/Committee Members: Fong, Dunne (chair), Firestein, Bonnie (internal member), Kwan, Kelvin (internal member), School of Graduate Studies.
Subjects/Keywords: Ovaries – Cancer – Treatment; Cell and Developmental Biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Christensen, Chase Tyler, 1. (2020). Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/64051/
Chicago Manual of Style (16th Edition):
Christensen, Chase Tyler, 1992-. “Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer.” 2020. Masters Thesis, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/64051/.
MLA Handbook (7th Edition):
Christensen, Chase Tyler, 1992-. “Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer.” 2020. Web. 05 Mar 2021.
Vancouver:
Christensen, Chase Tyler 1. Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer. [Internet] [Masters thesis]. Rutgers University; 2020. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64051/.
Council of Science Editors:
Christensen, Chase Tyler 1. Phytochemicals and repurposed, FDA approved drugs show potential as a cost effective combination treatment for ovarian cancer. [Masters Thesis]. Rutgers University; 2020. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64051/
Rutgers University
3.
Oni, Eileen N.
Elucidating the contributions of genetic variants associated with addiction phenotypes.
Degree: PhD, Cell and Developmental Biology, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/51388/
► Genome-wide association studies have identified several loci with variant sequences that are correlated with the risk of nicotine addiction and alcohol use disorders (AUD), however,…
(more)
▼ Genome-wide association studies have identified several loci with variant sequences that are correlated with the risk of nicotine addiction and alcohol use disorders (AUD), however, little is known about the cellular mechanisms underlying these genetic variants. Drugs such as nicotine mediate addiction behaviors via the activation of nicotinic acetylcholine receptors (nAChR). We first prepared subject-specific induced pluripotent stem cells (iPSC) from donors homozygous for either the major (D398) or the minor (N398) allele of the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in the CHRNA5 gene encoding the nAChR 5 subunit. To understand the impact of the N398 variant in human derived cells, we differentiated iPSCs to midbrain-like dopamine (DA) or glutamatergic neurons and then tested their functional properties and response to nicotine. Neurons from both variants demonstrated physiological and biochemical properties consistent with mature neuronal function. Results show that N398 variant midbrain-like DA neurons differentially express genes associated with ligand receptor interaction and synaptic function. The N398 neuronal population responded more actively with an increased excitatory postsynaptic current response upon the application of nicotine in both midbrain-like DA and glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine doses (0.1 ïM, concentrations of nicotine similar to those of heavy smokers) with greater frequency and amplitude and rapid desensitization, consistent with previous analyses of N398-associated nicotinic receptor function. Additionally, to understand the impact of AUD variants in humans, we prepared iPSCs from four subjects diagnosed with AUD and carrying three SNPs within the KCNJ6 gene (minor alleles of rs702859, rs702860, and rs2835872) encoding the potassium inward rectifying GIRK2 channel. We differentiated iPSCs into neural stem cells (NSCs) and all were positive for NSC markers (SOX2, Nestin, and Musashi). To model acute alcohol exposure, we exposed NSCs to medium containing 75 mM ethanol. To test whether this concentration would alter NSC growth dynamics, we assessed the cell viability, size, and doubling time over 72 hrs of exposure to which there was no detectable change. From RNAseq gene expression experiments following a 24 hr treatment with or without ethanol, we have identified differential gene enrichment in genes involved in neural differentiation as well as predicted alternative splicing variants in the KCNJ6 gene. We have also begun to assess the neuronal activity using two sources of basal culture medium (BrainPhys [Stem Cell Technologies] and Neurobasal [Gibco]) following Neurogenin 2 lentiviral differentiation of iPSCs. We detected substantial calcium spiking in BrainPhys medium in comparison to Neurobasal medium though calcium imaging analysis. This suggests that BrainPhys medium provides a more sustainable culture environment for future experiments. Planned studies will utilize cultures grown in BrainPhys based medium to…
Advisors/Committee Members: Kwan, Kelvin Y (chair), Hart, Ronald P (internal member), Pang, Zhiping P (internal member), Tischfield, Jay A (outside member).
Subjects/Keywords: Molecular biology; Phenotype
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Oni, E. N. (2016). Elucidating the contributions of genetic variants associated with addiction phenotypes. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/51388/
Chicago Manual of Style (16th Edition):
Oni, Eileen N. “Elucidating the contributions of genetic variants associated with addiction phenotypes.” 2016. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/51388/.
MLA Handbook (7th Edition):
Oni, Eileen N. “Elucidating the contributions of genetic variants associated with addiction phenotypes.” 2016. Web. 05 Mar 2021.
Vancouver:
Oni EN. Elucidating the contributions of genetic variants associated with addiction phenotypes. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51388/.
Council of Science Editors:
Oni EN. Elucidating the contributions of genetic variants associated with addiction phenotypes. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51388/
Rutgers University
4.
Li, Ying, 1987-.
Gene regulation during central nervous system development and post-injury regeneration.
Degree: PhD, Biomedical Engineering, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/49255/
► Central nervous system (CNS) development and post-injury neurogenesis require accurate coordination of neural stem cell proliferation, progenitor cell differentiation, neuron, glia migration and maturation, and…
(more)
▼ Central nervous system (CNS) development and post-injury neurogenesis require accurate coordination of neural stem cell proliferation, progenitor cell differentiation, neuron, glia migration and maturation, and synapse formation between axons and dendrites. Such systems with high complexity require strict temporal and spatial control via several levels of regulation, in which the transcription regulation is one of the most critical steps. The developmental and injury-repair process involves over 18,000 genes, for majority of which the molecular mechanism governing their transcription remains largely unknown. In an attempt to address this question, four projects were conducted focusing on two levels of transcription regulation: i.e., chromatin modification, and the interaction of cis-acting regulatory sequences with trans-acting protein factors. Computational methods were adopted to analyze the sequences of the cis-elements and iii make predictions for their interacting transcription factors (TFs). The functional roles of these cis- and trans-elements were further determined in vivo and in vitro. The following findings are presented: 1) the function of DNA topoisomerase II beta (Top2b) in proper laminar formation and cell survival during retinal development; 2) the development of computational method for identifying gene regulatory networks involving enhancers and master TFs that are important in retinal cell differentiation; 3) the mechanism of Notch1 regulation in neural stem/progenitor cells via the interaction between Nkx6.1 and a CNS specific enhancer CR2 during the development of the spinal cord interneurons; and 4) the role of CR2 in aNSC activation after injury. Findings from this dissertation provide new insights into the molecular mechanisms underlying transcription regulation during CNS development and post-injury neurogenesis. They can also serve as a basis for future development of gene therapies and regenerative medicine for neurological disorders including spinal cord injury.
Advisors/Committee Members: Cai, Li (chair), Firestein, Bonnie (internal member), Grumet, Martin (internal member), Kwan, Kelvin (outside member), Rasin, Mladen-Roko (outside member).
Subjects/Keywords: Genetic regulation; Developmental neurobiology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, Ying, 1. (2016). Gene regulation during central nervous system development and post-injury regeneration. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/49255/
Chicago Manual of Style (16th Edition):
Li, Ying, 1987-. “Gene regulation during central nervous system development and post-injury regeneration.” 2016. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/49255/.
MLA Handbook (7th Edition):
Li, Ying, 1987-. “Gene regulation during central nervous system development and post-injury regeneration.” 2016. Web. 05 Mar 2021.
Vancouver:
Li, Ying 1. Gene regulation during central nervous system development and post-injury regeneration. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49255/.
Council of Science Editors:
Li, Ying 1. Gene regulation during central nervous system development and post-injury regeneration. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49255/
Rutgers University
5.
Zhou, Anbo, 1991-.
Understanding the functional impact of genomic variants.
Degree: PhD, Pipeline, 2020, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/64813/
► Structural variations (SV) can lead to DNA rearrangements and frequently cause diseases such as neurological disorders. SVs account for more total nucleotide changes and occur…
(more)
▼ Structural variations (SV) can lead to DNA rearrangements and frequently cause diseases such as neurological disorders. SVs account for more total nucleotide changes and occur more frequently than single nucleotide polymorphisms (SNPs) (Stankiewicz and Lupski, 2010). As we continue to gain knowledge, SV has surpassed SNPs in its effects on human evolution, population diversity, and genetic diseases (Stankiewicz and Lupski, 2010). Compared to SNP, SV is more challenging to study due to its complex configuration, large size, and repetitive arrangement. Meanwhile, sequencing technologies including Illumina and Oxford Nanopore sequencing platform are being actively developed to generate sequencing data of human whole genomes, which can then be analyzed to study genetic variations. This series of studies aims to employ contemporary sequencing technologies and computational workflows to unravel the functional impact of SVs.
Good tools are prerequisite to the successful execution of a job. My study starts from developing a pipeline construction tool called PipelineDog that can be used throughout the work. PipelineDog is a web-based integrated development environment (IDE) that represents a novel way to arrange and define workflows while promoting code scalability and reusability. I then apply established tools and workflows to analyze a 192-invidual cohort, surveying the large structural genetic etiology of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) co-occurrence. Lastly, the newly commercialized Nanopore sequencing technique was tested and evaluated on both existing and simulated data. The Nanopore sequencing is anticipated to improve the SV identification, as it generates longer reads and will enrich the SV determining evidence. I improved the overall SV identification accuracy by employing a random forest machine learning model to classify the combined dataset from different workflows. This analysis shed light on how to determine which SV identification workflow to use based on specific use cases for future projects.
Advisors/Committee Members: Veerzi, Mikeal (chair), Xing, Jinchuan (co-chair), Brzustowicz, Linda (internal member), Kwan, Kelvin (outside member), School of Graduate Studies.
Subjects/Keywords: Quantitative Biomedicine
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhou, Anbo, 1. (2020). Understanding the functional impact of genomic variants. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/64813/
Chicago Manual of Style (16th Edition):
Zhou, Anbo, 1991-. “Understanding the functional impact of genomic variants.” 2020. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/64813/.
MLA Handbook (7th Edition):
Zhou, Anbo, 1991-. “Understanding the functional impact of genomic variants.” 2020. Web. 05 Mar 2021.
Vancouver:
Zhou, Anbo 1. Understanding the functional impact of genomic variants. [Internet] [Doctoral dissertation]. Rutgers University; 2020. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64813/.
Council of Science Editors:
Zhou, Anbo 1. Understanding the functional impact of genomic variants. [Doctoral Dissertation]. Rutgers University; 2020. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/64813/
Rutgers University
6.
Patel, Misaal N., 1993-.
Therapeutic role of neurogenic transcription factors in spinal cord injury.
Degree: PhD, Biomedical Engineering, 2019, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/61904/
► Spinal cord injury (SCI) results in neuronal damage and glial scar formation, leading to loss of function and paralysis below the injury site. Although there…
(more)
▼ Spinal cord injury (SCI) results in neuronal damage and glial scar formation, leading to loss of function and paralysis below the injury site. Although there are assistive devices in the market, there are no therapeutics that promote complete repair and regeneration after SCI. Major hurdles in neural regeneration include a limited level of neurogenesis in the adult spinal cord, an inflammatory microenvironment that inhibits neurogenesis, axon regeneration, neuronal relay formation, and myelination at the injury site. Promoting endogenous neural stem and progenitor cells (NSPCs) for tissue regeneration represents a potential strategy for the treatment of SCI. However, adult NSPCs largely differentiate into glial cells and contribute to glial scar formation in the injured spinal cord. Using virus-mediated delivery system as a potential therapeutics, we examined the effects of neurogenic factors on SCI in a mouse model. We identified that neurogenic factors promote cell proliferation and activation of NSPCs by activating Notch and Nanog signaling pathways during the acute stage of SCI. These factors promote the generation of various types of neurons (e.g., glutamatergic and cholinergic interneurons) and inhibit the generation of GABAergic interneurons in the injured spinal cord. Importantly, during the chronic stage, the treatment reduces glial scar formation and dramatically improves functional locomotion. Collectively, these findings suggest the neurogenic factors represent promising therapeutic genes for the treatment of SCI and provide molecular insight for transcription factor-mediated functional recovery.
Advisors/Committee Members: Cai, Li (chair), Firestein, Bonnie (internal member), Pang, Zhiping (internal member), Kwan, Kelvin Y (outside member), Jiang, Peng (outside member), School of Graduate Studies.
Subjects/Keywords: Spinal cord – Wounds and injuries – Treatment
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Patel, Misaal N., 1. (2019). Therapeutic role of neurogenic transcription factors in spinal cord injury. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/61904/
Chicago Manual of Style (16th Edition):
Patel, Misaal N., 1993-. “Therapeutic role of neurogenic transcription factors in spinal cord injury.” 2019. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/61904/.
MLA Handbook (7th Edition):
Patel, Misaal N., 1993-. “Therapeutic role of neurogenic transcription factors in spinal cord injury.” 2019. Web. 05 Mar 2021.
Vancouver:
Patel, Misaal N. 1. Therapeutic role of neurogenic transcription factors in spinal cord injury. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61904/.
Council of Science Editors:
Patel, Misaal N. 1. Therapeutic role of neurogenic transcription factors in spinal cord injury. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/61904/
7.
Song, Zhichao, 1989-.
Epigenetic alterations during otic regeneration.
Degree: PhD, Neuroscience, 2018, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/57701/
► Spiral ganglion neurons (SGNs) of the cochlea are essential for relaying auditory signals to the brain. Loss of SGNs significantly contributes to hearing loss. Replacement…
(more)
▼ Spiral ganglion neurons (SGNs) of the cochlea are essential for relaying auditory signals to the brain. Loss of SGNs significantly contributes to hearing loss. Replacement of lost SGNS with otic progenitor cells is a potential strategy to alleviate hearing loss. Studies on regeneration have focused on gene expression networks that maintain self-renewal or promote differentiation, but changes in chromatin structure play an equally important role during regeneration. Understanding how the chromatin landscape regulates SGN differentiation in otic progenitors will accelerate efforts for cell replacement therapies. In the thesis, I reviewed the molecular and morphological changes during inner ear development, cells affected by hearing disorders and recent research progress in stem cell replacement therapies for hearing loss. To study inner ear regeneration, I employed an immortalized multipotent otic progenitor (iMOP) cell line, an otic fate-restricted cell type to study the chromatin changes that occur during neuronal differentiation. Under different culture conditions, iMOP cells self-renew and maintain an otic progenitor cell fate or differentiate into neurons that express neuronal markers and display SGN morphology. To study how chromatin changes affect transcription during iMOP neuronal differentiation, I studied the transcriptional activity of a pro-neural transcription factor, Neurogenin1 ( Neurog1). In iMOP cells, Neurog1 was enriched at the promoter of both cyclin-dependent kinase 2 (Cdk2) and neuronal differentiation (NeuroD1) genes. Changes in deposition of H3K9ac and H3K9me3 at the Cdk2 and NeuroD1 promoters suggested epigenetic alterations as iMOP cells transitioned between proliferation and differentiation. Chromatin changes at these promoters affected Neurog1 dependent transcriptional activity. In self-renewing iMOP cells, overexpression of Neurog1 increased Cdk2 to drive proliferation while knockdown of Neurog1 decreased Cdk2 to reduce proliferation. In differentiating cells, overexpression in Neurog1 in iMOP-derived neurons accelerated the acquisition of neuronal morphology and expression of Neurod1, while knockdown of Neurog1 prevented differentiation. My findings suggest that Neurog1 promotes either proliferation or neuronal differentiation, depending on histone modification at the promoter region of target genes. To further understand the effects of chromatin remodeling on otic neurogenesis, I studied the function of Chd7, a nucleosome repositioning protein that is upstream of Neurog1. Chd7 is associated with CHARGE syndrome, a disease that displays a constellation of symptoms including hearing loss. Chd7 mutant mice displayed defects in inner ear development and SGN formation. In iMOP cells, Chd7 expression increased as cells undergo neuronal differentiation. Knockdown of Chd7 prevented neuronal differentiation in iMOP cells. By performing Chd7 ChIP-seq in proliferating iMOP cells, Chd7 target genes were identified. Correlating the transcript levels of Chd7 target genes using RNA-seq data…
Advisors/Committee Members: Kwan, Kelvin Y (chair), School of Graduate Studies.
Subjects/Keywords: Epigenetics; Labyrinth (Ear)
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Song, Zhichao, 1. (2018). Epigenetic alterations during otic regeneration. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/57701/
Chicago Manual of Style (16th Edition):
Song, Zhichao, 1989-. “Epigenetic alterations during otic regeneration.” 2018. Doctoral Dissertation, Rutgers University. Accessed March 05, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/57701/.
MLA Handbook (7th Edition):
Song, Zhichao, 1989-. “Epigenetic alterations during otic regeneration.” 2018. Web. 05 Mar 2021.
Vancouver:
Song, Zhichao 1. Epigenetic alterations during otic regeneration. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2021 Mar 05].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57701/.
Council of Science Editors:
Song, Zhichao 1. Epigenetic alterations during otic regeneration. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57701/
. 
Open Access Theses and Dissertations
