Other Genetics and Genomics Commons^™

Homocysteine Thiolactone From Translation Proofreading Is An Endogenous Ligand For Cell-Cell Signaling By The Receptor Sdia, Lorenzo Eugenio Leiva, Roberto A. Zúñiga, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Several widespread mechanisms enable cellular communication and coordinate the behavior of bacterial populations. The modules responsible for cellular communication are often found in matching pairs: an enzyme that synthesizes a signal molecule and a specific receptor that decodes it. A notable exception is Escherichia coli SdiA, a homolog of known N-acyl-homoserine lactone (AHL) receptors, for which no corresponding AHL synthase exists. SdiA is an orphan receptor that enables cross-talk by sensing AHLs from other bacterial species. In this work, we investigated whether homocysteine thiolactone (HTL), an AHL-like molecule arising from a proofreading reaction of methionyl tRNA synthetase (MetRS) to correct …

Deconstructing Systemic Sclerosis Heterogeneity: From Patient Subtypes To Pathogenic Fibroblasts, Rezvan Parvizi

Dartmouth College Ph.D Dissertations

This thesis advances heterogeneity as the central barrier both to interpreting therapeutic response and to identifying the molecular regulators that drive fibrosis in systemic sclerosis (SSc). In SSc, heterogeneity is manifest at every level at which the disease can be measured: clinically, in the variable extent of skin and organ involvement; molecularly, in the distinct gene-expression programs that distinguish otherwise comparable patients; and cellularly, in the diverse fibroblast populations from which the fibrotic signal ultimately arises.

Leveraging longitudinal skin transcriptomics from a large cohort treated with mycophenolate mofetil (MMF), the first study demonstrates that intrinsic molecular subtypes are dynamic rather …

Mobile Genetic Elements Shape Microbial Diversity And Functions In Thawing Permafrost Soils, Jiarong Guo, Samuel T. N. Aroney, Guillermo Domínguez-Huerta, Derek Smith, Dean Vik, Carlos Owusu-Ansah, Akbar Adjie Pratama, Sergei Solonenko, Funing Tian, Cristina Howard-Varona, Zhi-Ping Zhong, Aminata Fofana, Garrett J. Smith, Suzanne B. Hodgkins, Dylan Cronin, Isogenie Field Teams 2010–2017, 2019, Emerge Coordinators, Ben J. Woodcroft, Gene W. Tyson, Virginia I. Rich, Matthew B. Sullivan, Simon Roux, Sarah C. Bagby, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Ecosystems are shaped by communities of microorganisms whose niches and impacts depend on functional profiles influenced by gene gains and losses. Culture-based experiments demonstrate that mobile genetic elements (MGEs) can mediate gene flux, but quantitative understanding of these dynamics in natural systems remains limited. Here we develop and apply a systematic, meta-omic framework to investigate MGEs in a complex natural system using an 8-year soil time series collected at Stordalen Mire, in Sweden’s thawing permafrost margin. In this climate-critical peatland, we identify ~2.1 million MGE recombinases across 89 microbial phyla and assess ecological distributions, affected functions, past mobility and current …

The Competition Between Splicing And 3′ Processing Shapes The Human Transcriptome, Lindsey V. Soles, Shuangyu Li, Liang Liu, Kristianna S.K. Sarkan, Erik G. Alvstad, Lusong Tian, Yoseop Yoon, Marielle Valdez, Ivan Marazzi, Yongsheng Shi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Eukaryotic pre-mRNA processing steps, including splicing and 3′ processing, are tightly coordinated, yet the underlying mechanisms remain incompletely understood. U1 snRNP has been proposed to inhibit 3′ processing at intronic polyadenylation (IPA) sites through a splicing-independent mechanism termed telescripting. In contrast, we discovered that disrupting splicing by using six different methods—targeting various key components such as U1 snRNP, U2 snRNP, U2AF, and SF3b—activates 3′ processing at thousands of IPA sites. Notably, splicing inhibition, especially of U1 snRNP, induced widespread premature transcription termination within gene bodies through both IPA-coupled and IPA-independent mechanisms. Inhibition of different splicing factors activated overlapping and distinct …

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Development Of Self-Assembled Polymeric Polyplexes For Microrna Delivery: Toward Treatment Of Alcohol-Associated Liver Disease, Marjina Akter Kalpana

Theses & Dissertations

Self-assembled polymeric polyplexes have the potential to serve as an RNA interference (RNAi) delivery platform for the combined inhibition of CXCR4 and miR-155 in the treatment of alcohol-associated liver disease (AALD). A central challenge in RNA delivery is balancing the extracellular stability of polyplexes, cellular uptake, and intracellular release of RNA cargo. We developed polymeric polyplexes using the CXCR4-antagonist polymer PAMD, designed to target CXCR4 on activated hepatic stellate cells (HSCs) and deliver therapeutic miRNA to activated Kupffer cells (KCs) in fibrotic liver. We improved the polyplexes by cholesterol modification of PAMD and by PEGylation of PAMD-Ch. The cholesterol modification …

A Persistent Homology Framework For Scrna-Seq: Assessing Clustering Robustness And Quantifying Preprocessing And Integration Effects On Topological Features., Jonah Daneshmand

Electronic Theses and Dissertations

As single-cell RNA sequencing (scRNA-seq) data expands, robust methods for integrating diverse datasets are critical. This dissertation applies Persistent Homology (PH), a technique from Topological Data Analysis (TDA), to a collection of scRNA-seq datasets spanning eight tissue types to quantify how data integration affects topological features and biological interpretability. We assessed global topological structure using Betti curves, Euler characteristics, and persistence landscapes across raw, normalized, and integrated data representations. Our analysis revealed a performance inversion: while conventional methods excelled on unintegrated data, high-granularity topological methods, particularly those sensitive to global data structure, became superior after integration. This suggests a synergy …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Immunological Surveillance Against Cancer Across Mammals, Orsolya Vincze, Piotr Minias, Alexandre Corthay, Fernando Colchero, Jean-François Lemaître, Louise Maille, Tamás Malkócs, Justus Hagemann, Dalia A. Conde, Samuel Pavard, Antoine M. Dujon, Beata Ujvari, Frédéric Thomas, Amy M. Boddy, Carlo C. Maley, Damien Chevallier, Tuul Sepp, Thomas Pradeu, Mathieu Giraudeau

Presidential Fellows Articles and Research

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class …

Genetic And Geographic Profiling Of Fragrance-Associated Badh2 Mutations In Rice From China, Laos, And Vietnam, Lenie A. Quiatchon-Baeza, Venea Dara Daygon, Mariafe N. Calingacion, Melissa A. Fitzgerald

The Philippine Agricultural Scientist

Fragrance in rice is a culturally and economically significant trait in Asia and around the world. This study aimed to develop a genetic and geographic profile of the fragrance-associated BADH2 mutations (badh2.1 and badh2.11) in 1,067 rice varieties from China, Laos, and Vietnam, which are part of the International Rice Genebank Collection. Seventy-three varieties were found to carry the common eight-base pair (bp) deletion in exon 7 of the genes (badh2.1, also known as badh2.7), primarily from indica varieties, with some belonging to japonica, javanica, and intermediate varieties. Conversely, 59 varieties possess the recently identified badh2 allele, badh2.11 (also known …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Breeding Biofortified Protein Rich Organic Pulses For Better Human Health, Sonia Salaria

All Dissertations

Pulse crops are dry grains of legumes, the second most consumed plant crops in the world after cereals. These crops are one of the primary sources of plant-based protein and contain high concentrations of pre-biotic carbohydrates, minerals and vitamins. Recognizing the health benefits of pulses intake, their demands as sustainable food and changes in people’s diet preferences for plant-based protein have increased awareness for pulses consumption. With this scenario, improving the nutritional profile of pulse crops for rich nutrition has been an opportunity for breeders to explore and tailor the available germplasm to develop nutrient dense pulses. Furthermore, the genomic …

Utilizing Pharmacogenomics To Improve Students' Self-Perception On The Interprofessional Competencies Of Roles And Responsibilities, And Teams And Teamwork, Amanda Brown, Moom R. Roosan, Robert Goldsteen, Scott D. Ochs, Reza Taheri

Pharmacy Faculty Articles and Research

Introduction

Pharmacogenomics (PGx) is an emerging discipline with the potential to revolutionize personalized medicine, but its successful implementation requires interprofessional collaboration. To address this need, a virtual interprofessional education (IPE) session was designed for student pharmacists and medical students to engage in a case-based learning experience.

Objective

The primary objective was to develop and implement an IPE activity focused on a patient case requiring PGx-guided dual antiplatelet therapy and to assess students' perceptions of two Interprofessional Education Collaborative (IPEC) Version 3 Core Competencies. A secondary objective was to identify key lessons from the session.

Methods

Pharmacist and physician faculty collaboratively …

Exploring Muslim American Attitudes Toward Genetic Testing: Perceptions, Barriers, And Ethical Considerations, Hannah Mahmoud

University Honors Theses

This thesis explores perceptions and attitudes toward genetic testing within the Muslim American community, a group often underrepresented in genomic research and public health discourse. Using a community-distributed digital survey, data was collected from 50 self-identified Muslim Americans on their familiarity with genetic testing, reproductive and ethical considerations, and the influence of religious factors. While only 18% had undergone genetic testing themselves, many were familiar through family or friends, and most expressed cautious interest—especially when results could influence future family planning. Education level, age, and religious values shaped both comfort and understanding.

A key theme was the desire for culturally …

Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales

Thinking Matters Symposium

Mesoderm specific transcript (Mest) expression in white adipose tissue (WAT) is variable in genetically identical mice. Previous studies have shown a connection between Mest high expression and propensity for fat mass expansion. WAT and liver crosstalk has been well documented with hormone-like peptides signaling and regulating important metabolic pathways. The aim of this study is to investigate the correlation between these circulating factors and Mest expression in mice after exposure to a high fat diet (HFD). A group of 120 C57B6/J mice, males and females, were exposed to a HFD (Western Diet, 40 kcal% fat) for 4 weeks (8-12 weeks …

Genomic Structure Among Populations Of A Regionally Rare Perennial Plant Indicates The Need For Reevaluation Of Management Units, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine

Faculty Journal Articles

Conservation of rare species often relies on the delineation of management units and genomic tools can now be applied for this purpose. However, this is not as common on a local scale, where populations are often small and fragmented, despite the utility of informing conservation and management practice at the regional level. We use a genotyping by sequencing (GBS) approach to assess the perennial riparian plant species Baptisia australis (Fabaceae) in Pennsylvania, where the taxon is at the edge of its natural distribution and considered threatened. In this system, we investigate whether sampled subpopulations exhibit genetic structure. We find that …

Investigating The Effects Of Sod1 Knockout On Oxidative Stress And Stress Coping Styles In Zebrafish Using Crispr Technology, Tai Prauner, Ryan Wong

Theses/Capstones/Creative Projects

Reactive oxygen species are byproducts of cellular metabolism that, when not efficiently neutralized, can damage DNA, proteins, and lipids. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide radicals into less harmful molecules. While its molecular function is well documented, the role of SOD1 in shaping stress-related behavior remains underexplored. This project aimed to establish foundational tools for studying the behavioral impact of SOD1 knockout across proactive and reactive stress-coping styles in zebrafish.

To support future gene-editing experiments, microinjection and breeding protocols were refined across wildtype AB, proactive, and reactive zebrafish lines. No embryos were injected with CRISPR-Cas9 …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …