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Articles 1 - 30 of 1351
Full-Text Articles in Life Sciences
Improving Molecular Diagnosis Of Suspected Mendelian Disorders With Rna Splicing Analysis, Joseph Krittameth Aicher
Improving Molecular Diagnosis Of Suspected Mendelian Disorders With Rna Splicing Analysis, Joseph Krittameth Aicher
Publicly Accessible Penn Dissertations
Exome sequencing is the most advanced standard-of-care genetic test for people with suspected Mendelian disorders. Yet, the diagnostic rate of exome sequencing is only 31%. RNA sequencing (RNA-seq) is a promising molecular test for detecting potentially pathogenic changes in RNA splicing as part of obtaining a molecular diagnosis. In this dissertation, I develop new computational tools and perform analyses towards improving how we detect these potentially pathogenic changes in RNA splicing with the goal of improving the molecular diagnostic rate. First, in Chapter 1, I review background on how we diagnose patients and how RNA splicing and RNA-seq could be …
Unlocking Compacted Heterochromatin Through Modulation Of Associated Proteins, Kelsey Elizabeth Mercado Kaeding
Unlocking Compacted Heterochromatin Through Modulation Of Associated Proteins, Kelsey Elizabeth Mercado Kaeding
Publicly Accessible Penn Dissertations
The hundreds of cell types that compose human body tissues contain identical genomes yet vary considerably in their gene activity and protein content. While the underlying blueprints that define these diverse cell types exist in all cells, a given cell’s specific transcriptomic and proteomic landscape is controlled by an incredibly complex system of gene regulatory complexes and epigenetic marks which promote activation of cell-type specific gene expression profiles and silence alternative cell fate genes. However, the mechanism by which specific genomic loci are silenced in different cell types is still not well understood. Here I strove to understand the vital …
How Do Your Genes Smell? Applying Genetic Tools To Understand Olfactory Perception, Marissa Lyn Kamarck
How Do Your Genes Smell? Applying Genetic Tools To Understand Olfactory Perception, Marissa Lyn Kamarck
Publicly Accessible Penn Dissertations
Many of the major milestones in understanding the olfactory system have arisen from research conducted in non-human animal models through the use of various genetic tools. While mammalian olfaction is largely conserved, there are several key differences in humans that suggest the necessity of studies directed at human olfaction. The human olfactory system has both genotypic variation and phenotypic variation, suggesting that, like in animal research, genetic tools are viable and vital for investigating human olfaction. We first address the basic questions of the human olfactory system, examining whether our assumptions based on animal olfaction are confirmed and attempting to …
Layers Of Maturation In Cortical Hierarchies, Adam Pines
Layers Of Maturation In Cortical Hierarchies, Adam Pines
Publicly Accessible Penn Dissertations
Hierarchies form critical scaffolds for top-down processing but are often multiplex. In the brain, multiple layers of complex hierarchies intersect, dissociate, and re-converge over the lifespan. Although aspects of local hierarchical organizations are well-mapped for sensory systems, the fashion by which hierarchical organization extends globally is unknown. Human neuroimaging provides a means by which to observe both the developmental emergence and functions of global neurohierarchical organization. Here, we leveraged these advances to distill multiple layers of hierarchical formation across diverse brain-tissue quantifications. We demonstrate that these layers form common and dissociable biomarkers of the developmental emergence of complex cognition. Our …
Blimp1 And Nr4a3 Transcription Factors Reciprocally Regulate Antitumor Car T-Cell Stemness And Exhaustion, Inyoung Jung
Blimp1 And Nr4a3 Transcription Factors Reciprocally Regulate Antitumor Car T-Cell Stemness And Exhaustion, Inyoung Jung
Publicly Accessible Penn Dissertations
Chimeric antigen receptor (CAR) T-cells have not induced meaningful clinical responses in solid tumor indications. Loss of T-cell stemness, poor expansion capacity and exhaustion during prolonged tumor antigen exposure are major causes of CAR T-cell therapeutic resistance. scRNA-sequencing analysis of CAR T-cells from a first-in-human trial in metastatic prostate cancer identified two distinct and independently validated cell states associated with antitumor potency or lack of efficacy. Low levels of the PRDM1 gene encoding the BLIMP1 transcription factor defined highly potent TCF7+CD8+ CAR T-cells, while enrichment of TIM3+CD8+ T-cells with elevated PRDM1 expression predicted poor outcome. PRDM1 single knockout promoted TCF7-dependent …
The Network Science Of Distributed Representational Systems, Harang Ju
The Network Science Of Distributed Representational Systems, Harang Ju
Publicly Accessible Penn Dissertations
From brains to science itself, distributed representational systems store and process information about the world. In brains, complex cognitive functions emerge from the collective activity of billions of neurons, and in science, new knowledge is discovered by building on previous discoveries. In both systems, many small individual units—neurons and scientific concepts—interact to inform complex behaviors in the systems they comprise. The patterns in the interactions between units are telling; pairwise interactions not only trivially affect pairs of units, but they also form structural and dynamic patterns with more than just pairs, on a larger scale of the network. Recently, network …
A Critical Role For Mrgprb4 Touch Neurons In A Skin-Brain Pathway For Stress Resilience, Melanie Schaffler
A Critical Role For Mrgprb4 Touch Neurons In A Skin-Brain Pathway For Stress Resilience, Melanie Schaffler
Publicly Accessible Penn Dissertations
Social touch can act as a stress buffer, reducing behavioral and physiological responses to stressful scenarios. However, the skin-brain mechanosensory pathways that promote stress resilience remain unknown. In this thesis, I investigated how Mrgprb4-lineage touch neurons in the skin of mice play a role in this soothing skin-brain circuit. Early life ablation and activation of Mrgprb4-lineage neurons did not impact pup ultrasonic vocalizations, a measurement of postnatal stress. However, I found that mice with an early life genetic ablation of Mrgprb4-lineage touch neurons display behaviors that suggest vulnerability to stress in adulthood. Chemogenetic activation of the Mrgprb4-lineage touch neurons with …
Role Of Type Ii Phosphatidylinositol 4-Kinases In Endosomal Tubule Dynamics During Melanosome Biogenesis, Yueyao Zhu
Role Of Type Ii Phosphatidylinositol 4-Kinases In Endosomal Tubule Dynamics During Melanosome Biogenesis, Yueyao Zhu
Publicly Accessible Penn Dissertations
Melanosomes are pigment cell-specific lysosome-related organelles (LROs) in which melanin pigments are synthesized and stored. Melanosome maturation requires biosynthetic delivery of melanogenic enzymes (e.g. TYRP1), transporters (e.g. OCA2), and SNAREs (e.g. VAMP7) from early endosomes (EEs). One essential pathway requires the multisubunit complex, BLOC-1, on EEs to generate tubular transport carriers to deliver cargos to melanosomes. The molecular mechanisms by which BLOC-1 facilitates tubule formation are not entirely known, but several studies suggest that phosphatidylinositol-4-phosphate (PtdIns4P) and the type II PtdIns-4-kinases, PI4KIIα and PI4KIIβ, may play a role. Moreover, PI4KIIα and PI4KIIβ interact respectively with AP-3 and AP-1, both of …
Control Of Thermogenesis By Nuclear Receptor Corepressors And Rev-Erbs In Brown Adipose Tissue, Hannah Joy Richter
Control Of Thermogenesis By Nuclear Receptor Corepressors And Rev-Erbs In Brown Adipose Tissue, Hannah Joy Richter
Publicly Accessible Penn Dissertations
Brown adipose tissue (BAT) is a key thermogenic organ, whose expression of Uncoupling Protein 1 (UCP1) and ability to maintain body temperature in response to acute cold exposure requires histone deacetylase 3 (HDAC3). HDAC3 exists in tight association with nuclear receptor corepressors NCoR1 and NCoR2 (also known as Silencing Mediator of Retinoid and Thyroid Receptors, or SMRT), but the functions of NCoR1/2 in BAT have not been established. This corepressor complex of HDAC3 and NCoR1/2 can interact with a variety of nuclear receptors, including REV-ERBa/b which are related nuclear receptors (NRs) that couple the molecular clock with metabolism. Here we …
Optical Imaging Of Tissue Physiology With Exogenous Contrast Agents, Sang Hoon Chong
Optical Imaging Of Tissue Physiology With Exogenous Contrast Agents, Sang Hoon Chong
Publicly Accessible Penn Dissertations
This thesis describes experiments and analyses which push the frontier per what one can learn from optically emitting exogenous contrast agents in living tissue. The first set of experiments concurrently measured cerebral blood flow and bothintravascular- and extravascular-tissue oxygen concentration in a rat brain during functional activation; the new instrumentation needed to collect this information used contrast agent phosphorescence lifetime to determine oxygen concentration and speckle contrast imaging to probe blood flow. The concurrent measurement of multiple physiological parameters with high temporal resolution (∼7 Hz) provided a unique opportunity to observe the interconnected dynamics of oxygen exchange, blood flow, and …
The Effects Of Platelet Signaling Inhibitors On Clot Development Under Flow, Yiyuan Zhang
The Effects Of Platelet Signaling Inhibitors On Clot Development Under Flow, Yiyuan Zhang
Publicly Accessible Penn Dissertations
GPVI is the first responder towards collagen surface and therefore, the role of GPVI in facilitating primary platelet deposition is well studied and unquestionable. However, whether it plays a part in secondary platelet deposition by binding with fibrin, thus facilitating further platelet activation remains a question. Depending on the experiment method and rationale behind it, different results and conclusion could be achieved, thus it calls for a method that could better recapitulate human blood system under in vitro setting with appropriate methods to inhibit GPVI.Indirect method incorporates Syk and Src family kinases (SFK) inhibitors; these molecules interfere with signaling from …
Taken By Storm: The Rise And Fall Of Tau From Microtubule-Associated To Aggregated To Degraded, Melina Theoni Gyparaki
Taken By Storm: The Rise And Fall Of Tau From Microtubule-Associated To Aggregated To Degraded, Melina Theoni Gyparaki
Publicly Accessible Penn Dissertations
Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases, known as tauopathies. Aggregated proteins are normally degraded by the cell’s protein degradation mechanisms, autophagy or the ubiquitin-proteasome system (UPS). In tauopathies, however, the efficiency of these degradation pathways becomes challenged by the abnormal accumulation of the tau protein, which consequently, does not get fully degraded. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far, visualizing the spatial distribution of …
A Systematic Analysis Of The Concordance Between Chromatin Accessibility And Gene Expression Changes, Karun Kiani
A Systematic Analysis Of The Concordance Between Chromatin Accessibility And Gene Expression Changes, Karun Kiani
Publicly Accessible Penn Dissertations
A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genome, which are thought to correspond to transcription factor binding events. In concert with RNA-sequencing, these data in principle enable such mappings; however, few studies have looked at their concordance over short duration treatments with specific perturbations. Here, we used tandem, bulk ATAC-seq and RNA-seq measurements from MCF-7 breast carcinoma cells to systematically evaluate the concordance between …
E7, Ptpn14, And Yap1: How Papillomaviruses Retain Cells In The Basal Epithelial Layer With Implications For Persistence And Carcinogenesis, Joshua Hatterschide
E7, Ptpn14, And Yap1: How Papillomaviruses Retain Cells In The Basal Epithelial Layer With Implications For Persistence And Carcinogenesis, Joshua Hatterschide
Publicly Accessible Penn Dissertations
Persistent human papillomavirus (HPV) infections cause about 4.5% of the human cancer burden. The HPV E7 oncoprotein is one of the primary drivers of HPV-mediated carcinogenesis and facilitates HPV replication. The most well-studied HPV E7 activity is inactivation of the retinoblastoma tumor suppressor (RB1), which dysregulates the cell cycle. However, there is substantial evidence to suggest that HPV E7 must have other activities in addition to RB1 inactivation. HPV E7 proteins from diverse HPV genotypes interact with the host cell tumor suppressor protein tyrosine phosphatase non-receptor 14 (PTPN14). Many HPV E7 proteins also direct PTPN14 for proteosome-mediated degradation. Through my …
The Role Of Neuropilin2a/B And Sema3fa In The Protoglomerular Targeting Of Zebrafish Olfactory Sensory Neurons, Ryan Pei-Yen Cheng
The Role Of Neuropilin2a/B And Sema3fa In The Protoglomerular Targeting Of Zebrafish Olfactory Sensory Neurons, Ryan Pei-Yen Cheng
Publicly Accessible Penn Dissertations
During development, zebrafish olfactory sensory neurons (OSNs) project axons from the olfactory epithelium to neuropil structures in the olfactory bulb (OB) known as protoglomeruli. OSNs expressing either OMP or TRPC2 exclusively project axons to two distinct, complementary sets of protoglomeruli. It is not known how differential protoglomerular targeting of these two populations is maintained. The guidance receptors nrp2a and nrp2b, along with their ligand sema3fa, were identified through RNAseq as potential candidates responsible for differential protoglomerular targeting of OMP- and TRPC2-class OSNs. Nrp2a and nrp2b are expressed in TRPC2-class OSNs, while sema3fa is expressed in OMP-class OSNs and OB. To …
Structural Studies Of Trpv5 Modulation, Edwin Carl Fluck
Structural Studies Of Trpv5 Modulation, Edwin Carl Fluck
Publicly Accessible Penn Dissertations
Calcium homeostasis is a highly regulated process in the body. Transient receptor potential vanilloid 5 (TRPV5) is a calcium selective ion channel that is responsible for the regulation of calcium reabsorption in the kidney. TRPV5 has been shown to be the essential for maintaining this calcium homeostasis and is implicated in disorders including hypercalciuria and kidney stone disease. However, little is known about the structural basis for mechanisms of TRPV5 regulation. Therefore, we aimed to address questions surrounding TRPV5 structure and regulation by solving cryo-electron microscopy (cryo-EM) structures of TRPV5 under various conditions. Specifically, we focused on regulation by low …
Prevotella Phylogeny: Genomic And Molecular Insights Into The Role Of The Human Commensal Prevotella In Cystic Fibrosis, Prioty Ferheen Sarwar
Prevotella Phylogeny: Genomic And Molecular Insights Into The Role Of The Human Commensal Prevotella In Cystic Fibrosis, Prioty Ferheen Sarwar
Publicly Accessible Penn Dissertations
The genus Prevotella comprises of a diverse set of gram-negative anaerobes that are implicated in both health and disease. Prevotella is a common human commensal of various anatomic sites but can also be associated with the dysbiotic microbiomes of various chronic inflammatory diseases. Due to it’s association with both commensalism and disease, the role of Prevotella in disease progression is unclear. However, Prevotella has shown immunomodulatory potential, the ability to change the metabolic microenvironment and other cytotoxic phenotypes in both in vitro and in vivo studies. Despite this, Prevotella remains understudied both at the genomic and phenotypic levels. In this …
Regulation Of Genome Topology In Notch-Mutated Cancers, Yeqiao Zhou
Regulation Of Genome Topology In Notch-Mutated Cancers, Yeqiao Zhou
Publicly Accessible Penn Dissertations
Spatiotemporal regulation of gene expression governs cellular development and malignant transformation. Compared to the understanding of cis-regulatory elements on the linear chromatin, our knowledge about the three-dimensional (3D) organization of the human genome is still limited. Recent advances in chromatin conformation capture techniques coupled with high-throughput sequencing and fluorescence in situ hybridization combined with high-content microscopy greatly advanced the mapping of 3D genome at kilo-base resolutions. However, the mechanisms of the establishment and maintenance of genome folding and the implications of their disruption in cancer are largely unexplored. Moreover, besides a few architectural proteins, the roles of other transcription factors …
Peripheral Neuronal Encoding Of Pleasurable Social Touch, Leah J. Elias
Peripheral Neuronal Encoding Of Pleasurable Social Touch, Leah J. Elias
Publicly Accessible Penn Dissertations
Pleasurable touch during social behavior is key to building familial bonds and meaningful connections. As revealed by a global pandemic, isolation from these social contacts can have devastating effects on mental health. Yet, the identity and role of sensory neurons that transduce social touch remain unknown, limiting our understanding of what makes social touch beneficial and pleasurable, and therefore what goes wrong when it is missing or perturbed. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice, however, these neurons have never been implicated in any natural social behaviors. Here, we study …
Single Molecule Approaches To Studying Tau Function And Dysfunction, Sanjula Wickramasinghe
Single Molecule Approaches To Studying Tau Function And Dysfunction, Sanjula Wickramasinghe
Publicly Accessible Penn Dissertations
Tau is an intrinsically disordered protein found mainly in neurons, composed of four main domains, the N-terminal domain, the proline rich region, the microtubule binding region, and the C-terminal domain. Tau regulates the dynamic instability of microtubules by facilitating the polymerization of tubulin. Tau is also a key component of the aggregates found in several neurodegenerative diseases collectively known as tauopathies, the most prevalent of which is Alzheimer’s disease. In this disease pathology, normally soluble tau aggregates to form insoluble neurofibrillary tangles. The presence of aggregated tau spreads from one region of the brain to another suggesting that tau propagates …
The Impact Of Host Phenology On Parasite Transmission And Evolution, Hannelore Macdonald
The Impact Of Host Phenology On Parasite Transmission And Evolution, Hannelore Macdonald
Publicly Accessible Penn Dissertations
Parasite fitness is tightly controlled by host ecology. The timing of seasonal host activities, or host phenology, likely impacts parasite fitness by determining transmission between infected and uninfected hosts. Changes in host phenology are also expected to drive parasite adaptation in many disease systems, yet the quantitative and qualitative impact of phenology remains under-explored. The overarching goal of this dissertation is to develop theory on how host phenology impacts both parasite transmission and parasite evolution. A novel modelling framework was developed to study how tick life-stage phenology impacts the transmission of Borrelia burgdorferi in the Lyme disease system. This study …
Sodium Hydrogen Exchanger 1 Enhances Antitumor Activity Of Nk-92 Natural Killer Cells, Yaoyu Gong
Sodium Hydrogen Exchanger 1 Enhances Antitumor Activity Of Nk-92 Natural Killer Cells, Yaoyu Gong
Publicly Accessible Penn Dissertations
Adoptive cell transfer immunotherapy has remarkable efficacy against some hematological malignancies. However, its efficacy in solid tumors is limited by the adverse tumor microenvironment (TME) conditions, most notably that acidity inhibits T and NK cell mTORC1 activity and impairs cytotoxicity. In several reported studies, systemic buffering of tumor acidity enhanced the efficacy of immune checkpoint inhibitors. Paradoxically, we found in a Myc-inducible hepatocellular carcinoma model that buffering increased tumor mTORC1 activity, negating inhibition of tumor growth by anti-PD1 treatment. To avoid such adverse effects of systemic buffering favoring tumor growth, we overexpressed activated RHEB in the human NK-92 cell line, …
Engineering Controllable And Efficient Base Editors By Targeted Manipulation Of Dna Deaminases, Kiara Nicole Berrios Adorno
Engineering Controllable And Efficient Base Editors By Targeted Manipulation Of Dna Deaminases, Kiara Nicole Berrios Adorno
Publicly Accessible Penn Dissertations
Base editors (BEs) combine DNA deaminase mutator activity with CRISPR-Cas localization to create targeted point mutations in genomic DNA. Current approaches with BEs have enabled single-base alterations for several applications, including modeling and correction of disease alleles, crop engineering, and gene diversification. However, two major challenges limit their applicability: (1) moderate editing efficiency and (2) off-target mutagenesis of DNA and RNA. Here, we leverage our mechanistic knowledge into DNA deaminases to separately address both challenges. For one, nature has evolved DNA deaminases with suboptimal activity to achieve their role in immunity and minimize genomic instability. By deriving and characterizing hyperactive …
Inference Of Shared Genetic Architecture With Genome-Wide Association Data, Jianqiao Wang
Inference Of Shared Genetic Architecture With Genome-Wide Association Data, Jianqiao Wang
Publicly Accessible Penn Dissertations
Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits. Many complex traits and diseases share common genetic architecture. Studying the shared genetic architecture provides valuable insights into the underlying disease mechanisms. In this dissertation, we develop several statistical methods for investigating the shared genetic architecture based on GWAS data. We first discuss the quantification and estimation of the shared genetic architecture based on genetic covariance, which is defined as the underlying covariance of the genetic effects. We develop a unified approach to robust estimation and inference for genetic covariance of general outcomes that can be …
A Tale Of Two Transgenes: Aav-Dystrophin And Aav-Spike Reveal Common Themes For Gene Therapy And Vaccines, Christopher Greer
A Tale Of Two Transgenes: Aav-Dystrophin And Aav-Spike Reveal Common Themes For Gene Therapy And Vaccines, Christopher Greer
Publicly Accessible Penn Dissertations
Adeno-associated viruses (AAVs) are non-pathogenic, replication defective viruses that can facilitate long-term gene transfer to a variety of tissues in vivo. However, the limited DNA packaging capacity of AAV (~5 kb) poses challenges for the transfer of large genes. Additionally, while AAV is a minimally immunogenic viral vector, the risk of potential immune response against exogenous, AAV-delivered transgene products isn’t fully understood. Here I describe two in vivo AAV-mediated gene transfer projects that utilize engineered, miniaturized versions of larger genes to overcome the AAV packaging capacity for the disparate purposes of gene therapy for Duchenne muscular dystrophy and vaccination against …
The Role Of Working Memory In Implementing Computational Elements Of Visuo-Spatial Decision-Making, Kyra Schapiro
The Role Of Working Memory In Implementing Computational Elements Of Visuo-Spatial Decision-Making, Kyra Schapiro
Publicly Accessible Penn Dissertations
Decision making is a dynamic process by which a person integrates sensory evidence with prior expectations to select an action to achieve a desired outcome. Often, this process requires working memory to hold and manipulate the relevant information. Working memory has several known limitations and models of implementation that have not been widely considered in the context of decision-making. For decisions regarding spatial stimuli, the dorsolateral prefrontal cortex (dlPFC) is likely to be essential. Activity in this area has been shown to relate to both decision making and working memory, and has led to concrete models of how spatial information …
Central Control Of Pain And Inflammation Through A Hunger Circuit, Michelle Lynne Klima
Central Control Of Pain And Inflammation Through A Hunger Circuit, Michelle Lynne Klima
Publicly Accessible Penn Dissertations
Homeostasis is established through bidirectional communication between the periphery and the central nervous system. To maintain homeostasis, some biological drives can become prioritized over others. This changing balance between biological drives encourages peak performance and survival. However, when homeostasis is disturbed, chronic inflammatory diseases such as obesity, chronic pain, and arthritis can arise. We became interested in understanding if competing biological drives could be leveraged for therapeutic purposes. Food restriction inhibits inflammation; therefore, we explored how hunger and feeding neural circuits affect responses to noxious agents. Our first study investigated the role of hunger to alleviate pain behavior. We found …
Elucidating The Role Of Hepatic Foxo1 Signaling In The Regulation Of Adipose Tissue Biology, Jaimarie Sostre
Elucidating The Role Of Hepatic Foxo1 Signaling In The Regulation Of Adipose Tissue Biology, Jaimarie Sostre
Publicly Accessible Penn Dissertations
The hepatic transcription factor forkhead box O1 (FOXO1) is a critical regulator of hepatic and systemic insulin sensitivity. Previous studies demonstrate that genetic inhibition of liver FOXO1 improves insulin sensitivity in both genetic and dietary mouse models of metabolic disease. Mechanistically, this is due in part to cell non-autonomous control of adipose tissue insulin sensitivity. However, the mechanisms mediating this liver-adipose tissue crosstalk remain ill-defined. This thesis work comprises of two studies that sought to determine the role of hepatic insulin signaling via FOXO1 regulation over adipose tissue biology. The brown adipose tissue’s (BAT) ability to increase energy expenditure has …
Multi-Omics Integration Through Single-Cell Copy Number Analysis In Cancer, Chi-Yun Wu
Multi-Omics Integration Through Single-Cell Copy Number Analysis In Cancer, Chi-Yun Wu
Publicly Accessible Penn Dissertations
Genetic and epigenetic alterations combine to drive cancer progression. Heterogeneous cell populations within tumors are associated with poor prognosis and outcomes. Copy number aberrations (CNAs), a genetic variant commonly occurring in tumors, are used as markers to detect subclones and reconstruct tumor phylogeny. Multi-omics integration between CNAs and other modalities on tumor subclones facilitates studying the interplay between genome and epigenome, and their effects on transcriptome. So far, there is still a lack of computational methods for the multi-omics integration of different types of single-cell and ST tumor sequencing data. Therefore, the aim of this thesis is to extract (allele-specific) …
Regulation Of Anterior Gene Expression In The Caenorhabditis Elegans Embryo, Jonathan Douglas Rumley
Regulation Of Anterior Gene Expression In The Caenorhabditis Elegans Embryo, Jonathan Douglas Rumley
Publicly Accessible Penn Dissertations
Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. Using time-lapse laser confocal imaging of wild type and RNAi-treated C. elegans embryos, we found that the expression of five anterior-specific genes depends on the Wnt pathway effectors pop-1/TCF and sys-1/β-catenin. We focused further on one of these anterior genes, ref-2/ZIC, a conserved transcription factor expressed …