Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

PDF

Theses/Dissertations

University of Pennsylvania

Discipline
Keyword
Publication Year
Publication

Articles 1 - 30 of 934

Full-Text Articles in Life Sciences

Gingival Mscs Improve Bone Phenotype In Ovariectomy-Induced Osteoporosis Via Programmed Cell Death Pathway, Sultan Alghaithi Dec 2019

Gingival Mscs Improve Bone Phenotype In Ovariectomy-Induced Osteoporosis Via Programmed Cell Death Pathway, Sultan Alghaithi

Dental Theses

Estrogen deficiency-related osteoporosis is a skeletal system disorder that affects women after menopause taking a toll on financial and health institutions. Gingival Mesenchymal Stem cells (GMSCs) are a distinctive population of dental tissue-derived stem cells that possess uniquely high proliferation abilities and are capable of self-maintenance and multipotent differentiation. Their use has been investigated in different disease model applications, including cutaneous wound healing models, colitis, and allergy-related inflammatory disease models, but their effect on the bone phenotype of ovariectomy-induced osteoporosis hasn’t been explored. In our study, we show that a single systemic infusion of GMSCs elevated the bone mass ...


New Periodontal Pathogens And Their Biogeography In Ex Vivo Biofilms, Fany B. Ocampo May 2019

New Periodontal Pathogens And Their Biogeography In Ex Vivo Biofilms, Fany B. Ocampo

Dental Theses

Background: About 35% of the oral microbiome remains uncultured due to limitations of conventional laboratory techniques. More than 200 of those phylotypes have been catalogued in the HOMD and a subset of them had been proposed as candidate periodontal pathogens. This segment of the microbiome merits further investigation, as it might harbor important pathogens that are currently overlooked. Objective: The objective of this study was to devise an imaging approach to study such phylotypes in the conditions most conducive to their growth and begin to unveil their ecological and biogeographical characteristics.

Methods: Previous work from the Teles Lab had identified ...


Surface Polysaccharides Promote Innate Immune Evasion By The Pediatric Pathogen Kingella Kingae, Vanessa Lynne Munoz Jan 2019

Surface Polysaccharides Promote Innate Immune Evasion By The Pediatric Pathogen Kingella Kingae, Vanessa Lynne Munoz

Publicly Accessible Penn Dissertations

The gram-negative coccobacillus Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a common etiological agent of osteoarticular infections and bacteremia in young children. The pathogenesis of K. kingae disease involves colonization of the posterior pharynx, invasion into the bloodstream, and dissemination to distant sites of infection. Previous studies have revealed that K. kingae produces a number of surface factors that may contribute to the pathogenic process, including a polysaccharide capsule and an exopolysaccharide. The purpose of this work was to determine the role of the K. kingae polysaccharide capsule and exopolysaccharide in promoting resistance to complement-mediated ...


Innate Immune Antagonism By Diverse Coronavirus Phosphodiesterases, Stephen Goldstein Jan 2019

Innate Immune Antagonism By Diverse Coronavirus Phosphodiesterases, Stephen Goldstein

Publicly Accessible Penn Dissertations

Coronaviruses comprise a large family of viruses within the order Nidovirales containing single-stranded positive-sense RNA genomes of 27-32 kilobases. Divided into four genera (alpha, beta, gamma, delta) and multiple newly defined subgenera, coronaviruses include a number of important human and livestock pathogens responsible for a range of diseases. Historically, human coronaviruses OC43 and 229E have been associated with up to 30% of common colds, while the 2002 emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) first raised the specter of these viruses as possible pandemic agents. Although the SARS-CoV pandemic was quickly contained and the virus has not returned, the ...


Automated Analysis Of Experience-Dependent Sensory Response Behavior In Caenorhabditis Elegans, Patrick Mcclanahan Jan 2019

Automated Analysis Of Experience-Dependent Sensory Response Behavior In Caenorhabditis Elegans, Patrick Mcclanahan

Publicly Accessible Penn Dissertations

Understanding how the internal state of an organism affects its response to stimuli is an important question of biology and key to understanding human neurobehavioral problems. With its tractable 302 neuron nervous system and complex behavioral repertoire, the roundworm Caenorhabditis elegans is well suited for neurobehavioral studies. In this work, I investigate the modulation of C. elegans touch response. The traditional gentle and harsh (nociceptive) touch assays involve manually delivering a stimulus to 1 mm long animals using an eyebrow or a metal wire, respectively. Using these simple assays, researchers have identified the genes and mechanoreceptor neurons mediating gentle and ...


Establishment And Regulation Of Epithelial Enhancers By P63, Enrique Lin Shiao Jan 2019

Establishment And Regulation Of Epithelial Enhancers By P63, Enrique Lin Shiao

Publicly Accessible Penn Dissertations

The transcription factor p63 is a key mediator of epidermal commitment, development, and differentiation. Point mutations in p63 in human patients lead to developmental defects, including orofacial clefting, one of the most common congenital defects in humans. To date, knowledge is limited about how pivotal is p63’s role in human craniofacial development, due in part to a lack of tractable models to study de novo expression of p63 and its role at developmentally regulated genes. Using an inducible trans-differentiation model, combined with epigenomic sequencing and multi-cohort meta-analysis of GWAS data, we show that p63 establishes enhancers at craniofacial development ...


Event Structure In Vision And Language, Alon Hafri Jan 2019

Event Structure In Vision And Language, Alon Hafri

Publicly Accessible Penn Dissertations

Our visual experience is surprisingly rich: We do not only see low-level properties such as colors or contours; we also see events, or what is happening. Within linguistics, the examination of how we talk about events suggests that relatively abstract elements exist in the mind which pertain to the relational structure of events, including general thematic roles (e.g., Agent), Causation, Motion, and Transfer. For example, “Alex gave Jesse flowers” and “Jesse gave Alex flowers” both refer to an event of transfer, with the directionality of the transfer having different social consequences. The goal of the present research is to ...


Multiple Feedback Mechanisms Fine-Tune Rho Signaling To Regulate Morphogenetic Outcomes, Katy Lauren Ong Jan 2019

Multiple Feedback Mechanisms Fine-Tune Rho Signaling To Regulate Morphogenetic Outcomes, Katy Lauren Ong

Publicly Accessible Penn Dissertations

Rho signaling is a conserved mechanism for generating forces through activation of contractile actomyosin. How this pathway is tuned to produce different morphologies of cells and tissues is poorly understood. In the Drosophila embryonic epithelium, I investigated how Rho signaling controls force asymmetries to drive morphogenesis. Specifically, I studied a distinctive morphogenetic process termed “alignment”. This process of coordinated cell shape changes results in a unique cell geometry of rectilinear cells connected by aligned cell-cell contacts. I found that this rearrangement is initialized by contractility of actomyosin cables that elevate the local tension along aligning interfaces. Curiously, I find that ...


The Regulation Of Egfr Signaling And Kras Tumorigenesis By Receptor Palmitoylation, Akriti Kharbanda Jan 2019

The Regulation Of Egfr Signaling And Kras Tumorigenesis By Receptor Palmitoylation, Akriti Kharbanda

Publicly Accessible Penn Dissertations

Non-Small Cell Lung Cancer (NSCLC) is often characterized by mutually exclusive mutations in epidermal growth factor receptor (EGFR) or KRAS. The mutual exclusivity of these mutations is due to synthetic lethality, revealing a potential therapeutic vulnerability if possible to selectively activate EGFR in KRAS mutant cells. This thesis work demonstrates a previously unidentified mechanism of EGFR signal regulation through palmitoylation, the addition of the 16-carbon palmitate. The palmitoyltransferase, DHHC20, catalyzes this palmitoylation to Cys1025, Cys1122 and Cys1034 on the C-terminal tail of EGFR. Loss of EGFR palmitoylation leads to hyperactivation of the receptor, but decreased cell growth of KRAS mutant ...


Mass Spectrometry: An Ideal Method For Rna Modification Analysis, Samuel Peter Wein Jan 2019

Mass Spectrometry: An Ideal Method For Rna Modification Analysis, Samuel Peter Wein

Publicly Accessible Penn Dissertations

Currently there is no good way to measure and find the exact location of multiple RNA modifications. Existing technology can effectively find single varieties of modifications, but cannot identify co-occurrence. As the field of proteomics has shown, mass spectrometry is a powerful and versatile technique assessing broad ranges of chemical modifications in the context of the cellular environment. In this project I used our expertise in proteomics to build a mass spectrometry based platform for identifying RNA modifications. I have since set up both software and analytical platforms querying RNA modifications, and used this platform to survey human tRNA samples ...


Influence Of Landscape Spatial Patterns And Land Use Planning On Grassland Bird Habitat Occupancy In Chester County, Pennsylvania, M. Zoe Warner Jan 2019

Influence Of Landscape Spatial Patterns And Land Use Planning On Grassland Bird Habitat Occupancy In Chester County, Pennsylvania, M. Zoe Warner

Publicly Accessible Penn Dissertations

Throughout their range, North American grassland birds as a group have shown steeper and more widespread population declines than any other avian guild. Grassland bird decline corresponds to habitat loss, landscape fragmentation, agricultural intensification, and changes in land management. In areas where farmland is being converted, the presence or absence of grassland birds can be used to assess the availability of habitat across the landscape. Chester County in southeastern Pennsylvania has historically had an agricultural economic base, but since the 1980s, steady population growth and economic diversification have reduced the amount of available agricultural land in the county. In the ...


The Mechanism Of Caspase-8-Mediated Gene Expression And Its Integral Role In Host Defense, Alexandra Delaney Jan 2019

The Mechanism Of Caspase-8-Mediated Gene Expression And Its Integral Role In Host Defense, Alexandra Delaney

Publicly Accessible Penn Dissertations

Caspase-8 is a key integrator of cell survival and cell death decisions during infection and inflammation. Additionally, caspase-8 has an important, but less understood, role in cell-intrinsic inflammatory gene expression. Macrophages lacking caspase-8 have defective inflammatory cytokine expression in response to bacterial infection or TLR stimulation. How caspase-8 regulates cytokine gene expression, and whether caspase-8-mediated gene regulation has a physiological role during infection remains poorly defined. In this thesis we demonstrate that both caspase-8 enzymatic activity and scaffolding functions play a role in control of inflammatory cytokine gene expression. Caspase-8 enzymatic activity mediates IKK phosphorylation and nuclear translocation of the ...


The Immunomodulatory Functions Of Diacylglycerol Kinase Zeta On Type 2 Immune Responses, Brenal Singh Jan 2019

The Immunomodulatory Functions Of Diacylglycerol Kinase Zeta On Type 2 Immune Responses, Brenal Singh

Publicly Accessible Penn Dissertations

Type 2 helper T cells (Th2) are beneficial for orchestrating protective immune responses against helminths but can also be pathogenic in settings of allergy and asthma. Weak TCR-mediated extracellular signal-regulated kinase (ERK) signals are thought to promote Th2 differentiation in vitro. However, it was unclear whether selective enhancement of specific TCR-mediated signal transduction pathways could suppress Th2 differentiation in vitro and block Th2 inflammation in vivo in a polyclonal setting. The lipid molecule diacylglycerol (DAG) is the main driver of TCR-mediated ERK activation. Here, we demonstrate that T cells lacking DAG kinase-ζ (DGKζ), a negative regulator of DAG, display impaired ...


The Role Of Calcineurin/Nfat Signaling In Fibroblast Homeostasis And Activation, Allyson Elizabeth Lieberman Jan 2019

The Role Of Calcineurin/Nfat Signaling In Fibroblast Homeostasis And Activation, Allyson Elizabeth Lieberman

Publicly Accessible Penn Dissertations

Fibroblast activation is a crucial step in tumor growth and metastatic progression; activated fibroblasts remodel extracellular matrix (ECM) in primary tumor and metastatic microenvironments, exerting both pro- and anti-tumorigenic effects. However, the intrinsic mechanisms that regulate the activation of fibroblasts are not well defined. The signaling axis comprising the calcium-activated Ser/Thr phosphatase calcineurin (CN), and its downstream target nuclear factor of activated T cells (NFAT), has been shown to play important roles in in endothelial and immune cell activation, but its role in fibroblasts is not known. We have shown that deletion of CN in fibroblasts in vitro results ...


Investigating The Role Of The Human Naip/Nlrc4 Inflammasome In Host Defense Against Gram-Negative Bacterial Infection, Valeria M. Reyes Ruiz Jan 2019

Investigating The Role Of The Human Naip/Nlrc4 Inflammasome In Host Defense Against Gram-Negative Bacterial Infection, Valeria M. Reyes Ruiz

Publicly Accessible Penn Dissertations

Inflammasomes are key multiprotein intracellular complexes that mediate host defense against pathogenic microorganisms by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) sense components of the type III secretion system (T3SS) and flagellar apparatus. Upon sensing of bacterial components, NAIPs recruit the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4). The resulting NAIP/NLRC4 inflammasome then recruits and activates caspase-1. Active caspase-1 mediates processing and secretion of IL-1 family cytokines and a proinflammatory cell death termed pyroptosis. In mice, bacterial ligands for four of seven distinct NAIPs ...


A Mendelian Disease Of Autoimmunity Reveals Gimap5 As A Novel Member Of The Ragulator Complex, Michael Alexander Leney-Greene Jan 2019

A Mendelian Disease Of Autoimmunity Reveals Gimap5 As A Novel Member Of The Ragulator Complex, Michael Alexander Leney-Greene

Publicly Accessible Penn Dissertations

The incidence of autoimmune diseases, many of which lack effective treatments, is rapidly increasing in the developed world. Mendelian diseases allow the study of autoimmunity in humans, enabling new insights into the underlying pathology. In this study, I have identified a patient cohort suffering from a novel recessive Mendelian disease of immune dysregulation characterized by severe lymphopenia, splenomegaly, thrombocytopenia and liver failure. Whole exome sequencing revealed mutations in GIMAP5, a small GTPase primarily expressed in T, NK and endothelial cells. The missense mutations in these patients destabilize the protein in vitro and lead to a near complete loss of protein ...


Continuum Modeling Of Cell-Extracellular Environment Interaction, Xuan Cao Jan 2019

Continuum Modeling Of Cell-Extracellular Environment Interaction, Xuan Cao

Publicly Accessible Penn Dissertations

To perform functions such as proliferation, differentiation, and locomotion, living cells establish stable attachments to the extracellular matrix (ECM) via the formation of specialized receptor mediated contact foci, through which they sense the mechanical stimuli from the ECM and adapt their cytoskeleton structures. The cellular contraction, on the other hand, may induce dramatic structural changes to the local extracellular environment, particularly for the fibrous matrices. The main goal of this thesis is to understand the cell-ECM interaction and cell-cell interaction, which lays the foundation to address the role of mechanical stimuli in several physiological and pathological processes such as cell ...


The Genetic Makings Of The Superorganism, Michael Warner Jan 2019

The Genetic Makings Of The Superorganism, Michael Warner

Publicly Accessible Penn Dissertations

The evolutionary transition to eusociality entailed the origin of caste-based division of labor along with novel communication systems to regulate colony division of labor. Despite many recent studies on the genetic mechanisms underlying the transition to eusociality, or superorganismality, it is still largely unknown what genes are important, whether or not similar sets of genes are used in distinct origins of eusociality, and how related genes evolve. In this thesis, I perform large-scale RNA-sequencing experiments to identify genes underlying caste-based division of labor and the social regulation of larval development. I incorporate population genomic data to investigate the selective pressures ...


Nuclear Envelope Rupture And Genomic Instability In Cancer, Yuntao Xia Jan 2019

Nuclear Envelope Rupture And Genomic Instability In Cancer, Yuntao Xia

Publicly Accessible Penn Dissertations

Cell migration through narrow interstitial space in tissues is commonly seen in both physiological and pathological conditions. The bulky stiff nucleus in the cell becomes a barrier during constricted migration making such process pore-size dependent with smaller pores exponentially alleviate the passage capability. However, in some cases, cells actively deform their nuclei to squeeze through constrictions, during which nuclear envelope can rupture. As key intracellular processes such as DNA replication and transcription take place in the nucleus, the consequences of nuclear envelope rupture become intriguing.

In the past five years, we have observed increased DNA damage, cell cycle delay and ...


Non-Canonical Functions Of The Bacterial Sos Response, Amanda Samuels Jan 2019

Non-Canonical Functions Of The Bacterial Sos Response, Amanda Samuels

Publicly Accessible Penn Dissertations

DNA damage is a pervasive environmental threat, as such, most bacteria encode a network of genes called the SOS response that is poised to combat genotoxic stress. In the absence of DNA damage, the SOS response is repressed by LexA, a repressor-protease. In the presence of DNA damage, LexA undergoes a self-cleavage reaction relieving repression of SOS-controlled effector genes that promote bacterial survival. However, depending on the bacterial species, the SOS response has an expanded role beyond DNA repair, regulating genes involved in mutagenesis, virulence, persistence, and inter-species competition. Despite a plethora of research describing the significant consequences of the ...


Identification And Functional Characterization Of Novel Determinants Of The Somatotropes And Lactotrope Lineages In The Anterior Pituitary, Michael Thomas Peel Jan 2019

Identification And Functional Characterization Of Novel Determinants Of The Somatotropes And Lactotrope Lineages In The Anterior Pituitary, Michael Thomas Peel

Publicly Accessible Penn Dissertations

The differentiation of the hormone-producing cell lineages of the anterior pituitary represents an informative model of mammalian cell fate determination. The generation and maintenance of two of these lineages, the growth hormone (GH) producing somatotropes and the prolactin (PRL) producing lactotropes, are dependent on the pituitary-specific transcription factor, POU1F1. While POU1F1 is expressed in both cell types, and plays a direct role in the activation of both the Gh and Prl genes, GH expression is restricted to somatotropes and PRL expression is restricted to lactotropes. These observations imply the existence of additional, cell type-enriched factors, that contribute to the somatotrope ...


Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim Jan 2019

Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim

Publicly Accessible Penn Dissertations

Liver transplantation is the main treatment for acute liver failure patients; however, there is an insufficient supply of donor livers. Since transplanting hepatocytes, the main liver cell type, provides therapeutic effect and can be a bridge to transplant or recovery, scientists are working on generating replacement hepatocytes from stem cells and other cell types through reprogramming protocols. Currently, replacement hepatocytes recapitulate a subset of natural hepatocyte features, yet are still in an immature state, as they have not silenced all immature hepatocyte genes and activated all mature hepatocyte genes. Consequently, replacement hepatocytes do not perform as well as natural hepatocytes ...


The Affiliative Social Relations Of Free-Ranging Rhesus Macaques In The Context Of Instability, Sam Larson Jan 2019

The Affiliative Social Relations Of Free-Ranging Rhesus Macaques In The Context Of Instability, Sam Larson

Publicly Accessible Penn Dissertations

Across primates, socially integrated individuals exhibit improved genetic fitness compared to their peripheral conspecifics. However, the mechanisms through which this disparity operates is unclear. One hypothesis is that social bonds mitigate the stressors imparted by environmental instability. To date, this relationship has gone critically unexamined, owing to the inability to anticipate and account for instability in prospective research design. In this dissertation, I evaluate this hypothesis within a population of free-ranging rhesus macaques (M. mulatta). I employ a long-term behavioral data set comprised of 691 unique individuals across 6 groups, followed from 1 to 8 years. I employ the tool-kit ...


Discovering Pathway And Cell Type Signatures In Transcriptomic Compendia With Machine Learning, Gregory Philip Way Jan 2019

Discovering Pathway And Cell Type Signatures In Transcriptomic Compendia With Machine Learning, Gregory Philip Way

Publicly Accessible Penn Dissertations

Gene expression measurements capture downstream biological responses to molecular perturbations. This systems biology perspective can be investigated using both supervised and unsupervised machine learning approaches to rapidly derive insight, including cell type and pathway signatures, from transcriptomic compendia. Machine learning applied to transcriptomic compendia can aid in biological discovery, hypothesis generation, and precision medicine. We introduce these topics and discuss their impact in Chapter 1. In Chapters 2-4, we describe and extend a supervised learning approach to detect aberrant gene and pathway activity in cancer. We apply this approach to identify patient tumors, cell lines, and patient derived xenograft models ...


Cortical And Subcortical Mechanisms For Sound Processing, Jennifer Blackwell Jan 2019

Cortical And Subcortical Mechanisms For Sound Processing, Jennifer Blackwell

Publicly Accessible Penn Dissertations

The auditory cortex is essential for encoding complex and behaviorally relevant sounds. Many questions remain concerning whether and how distinct cortical neuronal subtypes shape and encode both simple and complex sound properties. In chapter 2, we tested how neurons in the auditory cortex encode water-like sounds perceived as natural by human listeners, but that we could precisely parametrize. The stimuli exhibit scale-invariant statistics, specifically temporal modulation within spectral bands scaled with the center frequency of the band. We used chronically implanted tetrodes to record neuronal spiking in rat primary auditory cortex during exposure to our custom stimuli at different rates ...


Role Of The Nuclear Receptor Pparγ In Clear Cell Renal And Bladder Urotheial Carcinoma, Danielle Sanchez Jan 2019

Role Of The Nuclear Receptor Pparγ In Clear Cell Renal And Bladder Urotheial Carcinoma, Danielle Sanchez

Publicly Accessible Penn Dissertations

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) has a well-characterized role in the developmental process of adipogenesis and transcriptional regulation of lipid metabolism. However, its expression patterns and functions in various cancer subtypes are less understood. My studies investigate the role of PPARγ in two distinct cancers of the urinary tract: clear cell renal cell carcinoma (ccRCC) and bladder urothelial carcinoma (UC). In ccRCC, I hypothesized that PPARγ activity contributes to the aberrant lipid accumulation phenotype characteristic of this disease, thereby promoting tumor progression. Through ChIP-seq, I demonstrated that PPARγ and its heterodimeric DNA binding partner retinoid X receptor ...


Genetic Insights Into Latent Autoimmune Diabetes In Adults, Rajashree Mishra Jan 2019

Genetic Insights Into Latent Autoimmune Diabetes In Adults, Rajashree Mishra

Publicly Accessible Penn Dissertations

‘Latent autoimmune diabetes in adults’ (LADA) is a controversial subtype of diabetes characterized by initial insulin independency and the presence of diabetes associated autoantibodies. As a result, LADA is often misclassified and can represent 5-10% of apparent type 2 diabetes (T2D) cases and is potentially more prevalent than childhood-onset type 1 diabetes (T1D). Despite LADA sharing features with the two better characterized classic diabetes subtypes, the genetic etiology of LADA remains largely unknown. Once there is a more accurate definition of LADA, there will be an improvement in diabetes classification and consequently better treatment and therapeutic interventions. The objective of ...


The Effect Of Abstinence From Smoking On Stress Reactivity, Cheyenne Allenby Jan 2019

The Effect Of Abstinence From Smoking On Stress Reactivity, Cheyenne Allenby

Publicly Accessible Penn Dissertations

Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by the reliability of current available measures of stress. Functional magnetic reasoning imaging (fMRI) could provide a much-needed objective measure of stress reactivity. The goal of this dissertation is to contribute to the understanding of abstinence-induced changes in stress reactivity by examining neural, neuroendocrine (cortisol), and subjective measures of stress response during abstinence. In addition, this study investigated the influence of individual variation in nicotine metabolism rates on these measures of stress reactivity. Seventy-five treatment-seeking smokers underwent blood oxygen level ...


The Role Of P120catenin In The Initiation And Dissemination Of Pancreatic Cancer, Basil Bakir Jan 2019

The Role Of P120catenin In The Initiation And Dissemination Of Pancreatic Cancer, Basil Bakir

Publicly Accessible Penn Dissertations

Pancreatic cancer is the third leading cause of cancer mortality, the overwhelming majority of which is due to metastasis. The mechanisms of dissemination have been intensively studied, but questions remain as to how epithelial properties are regulated between the primary tumor site and destination as well as to how organotropic patterns of metastasis are determined. We demonstrate, using multiple complementary mouse models, that liver and lung metastatic organotropism in pancreatic cancer is dependent on p120catenin (p120ctn)-mediated epithelial identity. Monoallelic p120ctn loss accelerates KrasG12D-driven PanIN/PDAC formation and metastasis to the liver as well as being sufficient for E-CADHERIN-mediated cell ...


Detecting Ancient Balancing Selection: Methods And Application To Human, Katherine Siewert Jan 2019

Detecting Ancient Balancing Selection: Methods And Application To Human, Katherine Siewert

Publicly Accessible Penn Dissertations

Balancing selection can maintain genetic variation in a population over long evolutionary time periods. Identifying genomic loci under this type of selection not only elucidates selective pressures and adaptations but can also help interpret common genetic variation contributing to disease. Summary statistics which capture signatures in the site frequency spectrum are frequently used to scan the genome to detect loci showing evidence of balancing selection. However, these approaches have limited power because they rely on imprecise signatures such as a general excess of heterozygosity or number of genetic variants. A second class of statistics, based on likelihoods, have higher power ...