Genetics and Genomics Commons^™

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky

Faculty, Staff and Students Publications

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite …

Understanding Potassium Toxicity Stress Responses Of The Extremophyte Schrenkiella Parvula Using Systems Biology Approaches, Pramod Pantha

LSU Doctoral Dissertations

Schrenkiella parvula is an extremophyte model closely related to Arabidopsis thaliana and Brassica crops. Its natural habitat includes shores of saline lakes in the Irano-Turanian region. It has adapted to grow in soils rich in multiple salts including Na⁺ and K⁺. I have investigated the genetic basis for high K⁺ tolerance in plants using S. parvula as a stress tolerant model compared to the premier plant model, Arabidopsis thaliana which is highly sensitive to salt stresses using physiological, ionomic, transcriptomic, and metabolomic approaches. Under high K⁺ stress, root system architecture changes significantly compared to control …

Comparative Genomics Methods And Applications, Emily N. Alden

Biomedical Sciences ETDs

Virtually all fields of biology have benefited from the advancements in comparative genomics technologies, specifically in the study of evolution. In this dissertation I develop and use comparative genomic technologies to investigate the novel SARS-CoV-2 virus, assembly the first genome of the black lace domestic angelfish and identify germline genetic variants associated with altered breast cancer-specific survival. Our genome tiling array for the novel coronavirus presents a rapid and cost-effective method to sequence the entire viral genome and can be used to track the rapid evolution of viral variants in the population. The domestic angelfish is a member of the …

Human Population History At The Crossroads Of East And Southeast Asia Since 11,000 Years Ago, Tianyi Wang, Wei Wang, Guangmao Xie, Zhen Li, Xuechun Fan, Qingping Yang, Xichao Wu, Ling Qin, Fajun Li, Melinda A. Yang

Biology Faculty Publications

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …

Investigation Of Rack1 Effect On Mor Expression Using Crispr Technology, Zil Modi

Seton Hall University Dissertations and Theses (ETDs)

The µ-opioid receptor, MOR, is the primary target for exogenous and endogenous analgesics, such as morphine or oxycodone, used to relieve pain following physical trauma or invasive procedures. When opioid analgesics are utilized extensively, patients can develop tolerance heightening the risk of respiratory depression and subsequently death. MOR gene expression is known to be regulated by several transcription factors including poly-C binding protein 1, PCBP1, which also interacts with receptor for activated C kinase, RACK1. Using overexpression and siRNA RACK1 was shown to be inversely related to MOR expression. To further investigate the relationship of RACK1 and MOR expression, RACK1 …

Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn

Dissertations, Theses, and Capstone Projects

A long history of isolation coupled with complex topographic and ecological landscapes makes Madagascar ideal for exploring the historical factors that have shaped patterns of population diversity and endemism. Many species-level studies have suggested Late Quaternary climate change may have influenced population dynamics in the tropics, but Madagascar’s ecologically unique biomes or individual species properties may have driven idiosyncratic responses to these shifts. Using community-scale population genetic data I implement a hierarchical approximate Bayesian computation (hABC) approach to evaluate the degree of synchronous population expansion during glacial cycles across herpetofaunal assemblages both within and across discrete biomes and taxonomic groups. …

Evolution And Development Of The Seed Coat In Gymnosperms, Cecilia Zumajo

Dissertations, Theses, and Capstone Projects

Gymnosperms and angiosperms are the most abundant plant lineages on earth and constitute a turning point in the evolution of plants because they are at the origin of the seed, a key morphological and developmental novelty in the evolution of land plant. Although the morphological variation of the seed, across seed plants, may on its own, explain the complexity of this structure, the origin, and evolution are even more, the understanding of these topics is still under discussion. Evidence shows that previous studies have often lacked the component of gene expression, particularly in species that are not model species. The …

Overview Of The Microbiome Among Nurses Study (Micro-N) As An Example Of Prospective Characterization Of The Microbiome Within Cohort Studies, Christine Everett, Chengchen Li, Jeremy E. Wilkinson, Long H. Nguyen, Lauren J. Mciver, Kerry Ivey, Jacques Izard, Natalia Palacios, A. Heather Eliassen, Walter C. Willett, Alberto Ascherio, Qi Sun, Shelley S. Tworoger, Andrew T. Chan, Wendy S. Garrett, Curtis Huttenhower, Eric B. Rimm, Mingyang Song

Department of Food Science and Technology: Faculty Publications

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations and Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Identification And Comparison Of Arbuscular Mycorrhizal Fungi And Soil Microbiomes Between American Chestnuts And Surrounding Hardwoods, Sarah Andrews, Geoffrey Eger, Isabella Vahle

Symposium of Student Scholars

Background/Questions/Methods

The introduction of the Chinese chestnut blight in 1904 decimated native American chestnut (Castanea dentata (Marshall) Borkh.) populations. In this study we aim to: 1) document the location of individual chestnuts in our vicinity; 2) document healthy versus blight infected individuals; 3) characterize putative differences in the soil microbiome between infected and non-infected individuals, as well as between chestnuts and hardwood neighbors. With this information we hope to provide new insights into mechanisms that may enhance blight and fungal resistance in American chestnuts through the understanding of the interactions between the trees and their surrounding soil microbiome.

Soil …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Development Of In-Silico Pipelines For Identification And Characterization Of Biomarker Panels And Therapeutic Interventions In Gastro-Intestinal (Gi) Cancers, Pranita Atri

Theses & Dissertations

Gastro-intestinal (GI) malignancies, including gastric, colorectal, and pancreatic cancers, have maintained their high overall mortality due to a lack of prognostic and diagnostic biomarkers and potential therapeutic modalities. While efforts have been made to improve both early detection and therapeutic interventions in these cancers, failure of conventional approaches have proven to be a big challenge, and alternate approaches are needed. Computational biology approaches owing to lesser time and more per target success rate offer a unique solution here. The current study explored the use of computational biology techniques to study the various aspects relating to GI malignancies. First, we sought …

Genomics, Exometabolomics, And Metabolic Probing Reveal Conserved Proteolytic Metabolism Of Thermoflexus Hugenholtzii And Three Candidate Species From China And Japan, Scott C. Thomas, Devon Payne, Kevin O. Tamadonfar, Cale O. Seymour, Jian Yu Jiao, Senthil K. Murugapiran, Dengxun Lai, Rebecca Lau, Benjamin P. Bowen, Leslie P. Silva, Katherine B. Louie, Marcel Huntemann, Alicia Clum, Alex Spunde, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, I. Min Chen, Dimitrios Stamatis, T. B.K. Reddy, Ronan O’Malley, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos C. Kyrpides, Tanja Woyke, Emiley Eloe-Fadrosh, Trinity L. Hamilton, Paul Dijkstra, Brian P. Hedlund

Life Sciences Faculty Research

Thermoflexus hugenholtzii JAD2 , the only cultured representative of the Chloroflexota order Thermoflexales, is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for T. hugenholtzii JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of T. hugenholtzii JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing “Candidatus Thermoflexus japonica,” “Candidatus Thermoflexus tengchongensis,” and “Candidatus …

Has Maize Overtaken Our Reality? A Personal Briefing, Biochemical Comparison, Agrigenomics, And History Of Maize, Nader Pahlevan

Honors Theses

Maize (Zea mays ssp. Mays) is a revolutionary cereal grain that has raced to the world’s most popular staple crop, transforming societies and impacting history. This paper aims to build and portray the story maize has created through its journey to world domination. The important details that encompass this literature are maize’s cultural significance in my life’s story, the comparison of various starches broken down into amylose and amylopectin ratios, a summative historical account on maize’s spread throughout numerous parts of the old world, and the genetical analysis of maize that explains the key features that have led …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

The Diversity And Evolution Of Phenazine Biosynthesis Pathways In Enterobacterales, Christian Leise

Honors Theses

Enterobacterales is an order of Gram-negative bacteria that encompasses plant and animal pathogens and organisms of industrial importance. Some of these bacteria produce secondary metabolites classified as phenazines (Phz). Studies in other groups of microorganisms revealed that phenazines are redox-active and exhibit broad antibacterial, antifungal, and antiparasitic activity. Enterobacterales are known to produce phenazines, but details about the diversity, biochemistry, and function of phenazine metabolites in these organisms are missing. In this work, we screened the National Center for Biotechnology Information (NCBI) GenBank for genome sequences of phenazine-producing (Phz+) Enterobacterales. Additionally, genomes of Phz+ strains Pectobacterium carotovorum cc303 and …

Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (>90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum of genetic features and associated phenotypes. Despite recent advances in the transcriptomic characterization of PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific patterns of oncogenic dependency. To fully leverage advancements in next generation sequencing and functional genomics, we have sought to establish computational methodologies to aid in refined target discovery, and to develop a novel …

Mixture Model Approaches To Integrative Analysis Of Multi-Omics Data And Spatially Correlated Genomic Data, Ziqiao Wang

Dissertations and Theses (Open Access)

Integrative genomic data analysis is a powerful tool to study the complex biological processes behind a disease. Statistical methods can model the interrelationships of the involved gene activities through jointly analyzing multiple types of genomic data from different platforms (vertical integration), or improve the power of a study through aggregating the same type of genomic data across studies (horizontal integration). In this dissertation, we propose statistical methods and strategies for integrative multi-omics data in association analysis of disease phenotypes, with an emphasis on cancer applications.

We develop a new strategy based on horizontal integration by leveraging publicly available datasets into …

Validation Of Anti-Oxidative Stress Genes From Genome-Wide Screening Of Escherichia Coli, Carson Ercanbrack

Chemistry & Biochemistry Undergraduate Honors Theses

The primary purpose of this project is to evaluate the genes that play a role in the oxidative stress response in Escherichia coli. In doing so, the entire genome of E. coli was subject to throughput in which individual genes were determined to have a role in the bacteria’s oxidative stress response. Moreover, this project focused on the validation of the genes that were able to pass the initial throughput stage. The genes were subject to two forms of validation. In the first validation technique, candidate genes were overexpressed and minimum inhibitory concentrations of hypochlorous acid were taken. Following, a …

Dynamics Of Hybrid Zones At A Continental Scale, Bradley T. Martin

Graduate Theses and Dissertations

Hybridization has traditionally been viewed as a happenstance that negatively impacts populations, but is now recognized as an important evolutionary mechanism that can substantially impact the evolutionary trajectories of gene pools, influence adaptive capacity, and contravene or reinforce divergence. Physiographic processes are important drivers of dispersal, alternately funneling populations into isolation, promoting divergence, or facilitating secondary contact of diverged populations, increasing the potential for hybridization. In North America, glacial-interglacial cycles and geomorphological changes have provided a dynamic backdrop over the last two million years that promoted such oscillations of population contraction and expansion. These biogeographic processes have resulted in regional …

Understanding The Genetics Of Schizophrenia, Matthew Toohey

Thinking Matters Symposium

Schizophrenia has been considered heritable for a long time, but only with the advent of new technologies such as whole-genome sequencing and genome-wide association studies can we begin to identify specific molecular causes of schizophrenia. This poster will review some of the genetic variants that research groups have associated with schizophrenia. Current research has indicated that schizophrenia is a polygenic disease and has been linked to many genes. Some of these common risk variants are in protein coding sections of the DNA. These proteins are often linked to neurological development or immune system function. Other variants that have been associated …

307— Cooperation Of Selfish Genetic Elements In Stalk-Eyed Flies, Suhani Patel, Ben Mcpherson

GREAT Day Posters

SGEs are selfish genetic elements that increase the likelihood of their own transmission regardless of the host’s best interest. Transposable elements (TEs) and meiotic drivers are both types of SGEs. SGEs subsequently result in genetic conflict as they disrupt functional elements in the genome. We are working to better understand the cooperation of selfish genetic elements in Stalk-Eyed flies. Transposable elements are counteracted by small non-coding RNA molecules called piRNA. These RNA molecules work by reducing the expression of TEs by degrading TE RNA transcripts. Prior work in stalk-eyed flies has shown that TEs are expressed at a higher rate …

Annotation Of The Genome Of Drosophilia Ananassae, Landon Kehr

Celebration of Scholarship 2021

This project involves the use of software to annotate the genome of D. ananassae in collaboration with the Genomics Education Partnership. Annotations include coding regions and transcription start sites for specific genes that are homologous to D. melanogaster genes.

Comparative Genomics For D. Ananassae, Hailey Chang, Tia Watkins

Celebration of Scholarship 2021

The purpose of this project is to utilize comparative genomics tools to characterize specific genes in D. Ananassae. This is done in collaboration with the Genomics Education Partnership.

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

A Whole-Genome Scan For Association With Invasion Success In The Fruit Fly Drosophila Suzukii Using Contrasts Of Allele Frequencies Corrected For Population Structure, Laure Olazcuaga, Anne Loiseau, Hugues Parrinello, Mathilde Paris, Antoine Fraimout, Christelle Guedot, Lauren M. Diepenbrock, Marc Kenis, Jinping Zhang, Xiao Chen, Nicolas Borowiec, Benoit Facon, Heidrun Vogt, Donald K. Price, Heiko Vogel, Benjamin Prud'homme, Arnaud Estoup, Mathieu Gautier

Life Sciences Faculty Research

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic …