Genetic Processes Commons^™

Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay

Theses and Dissertations

The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …

A Family With Neuropathies And An Mfn2 Variant, Leah Miller

Larner College of Medicine Fourth Year Advanced Integration Teaching/Scholarly Projects

BACKGROUND: The axonal subtype of Charcot-Marie-Tooth (CMT2A) is commonly caused by dominant mutations in MFN2, which encodes a protein involved in mitochondrial dynamics and axonal transport. Over 100 variants in MFN2 are reportedly pathogenic. MFN2 dysfunction yields heterogenous neuropathies which can include optic atrophy, dysautonomia and diaphragmatic/airway dysfunction.

CASE REPORT: A 52-year-old man presented with a 10-year history of burning forefoot dysthesias and orthostasis. His examination revealed reduced sensation to light touch and pinprick distally with preserved strength and reflexes. NCS/EMG demonstrated mild, symmetric axonal polyneuropathy. Autonomic testing revealed orthostatic tachycardia and postganglionic sudomotor dysfunction. Laboratory evaluation for common causes …

Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene …

Gene Electrotransfer Of Fgf2 Enhances Collagen Scaffold Biocompatibility, Carly Boye, Kyle Cristensen, Kamal Asadipour, Scott Declemente, Michael Francis, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Tendon injuries are a common athletic injury that have been increasing in prevalence. While there are current clinical treatments for tendon injuries, they have relatively long recovery times and often do not restore native function of the tendon. In the current study, gene electrotransfer (GET) parameters for delivery to the skin were optimized with monophasic and biphasic pulses with reporter and effector genes towards optimizing underlying tendon healing. Tissue twitching and damage, as well as gene expression and distribution were evaluated. Bioprinted collagen scaffolds, mimicking healthy tendon structure were then implanted subcutaneously for biocompatibility and angiogenesis analyses when combined with …

How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir

Journal of Mind and Medical Sciences

Personalized treatment in oncology is the most innovative method of care. The best method to establish personalized treatment is by genetic characterization of the malignant cell.

Theoretically, the more detailed the characterization, the more effective the choice of treatment becomes. Currently, there are fast and relatively low-cost options that allow such genetic characterization. However, test results sometimes do not detect targetable alterations and, even if they do detect, the use of the treatment-alteration combination does not always generate a satisfactory oncological response.

The present paper aims to answer two questions. First, how targetable can the most common gene alterations in …

The Onset Of Exercise-Associated Hyponatremia And Individual Differences In Inappropriate Arginine Vasopressin Excretion: A Review Of Proposed Mechanisms, Michelle Stehman, Stephen A. Maris

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 10, 2021. Exercise-associated hyponatremia (EAH) has been reported to develop during endurance events such as triathlons and marathons. As these events become more popular, the incidence of developing EAH also increases. The development of EAH is commonly associated with the overconsumption of hypotonic fluids such as water and tends to be more prevalent in females. There is also evidence to suggest the inappropriate secretion of arginine vasopressin (AVP) leading to water retention may predispose an individual for developing EAH, especially when coupled with the overconsumption of fluids. Recent research …

Whole Genome Sequence Analysis Of Platelet Traits In The Nhlbi Trans-Omics For Precision Medicine Initiative, Amarise Little, Yao Hu, Quan Sun, Deepti Jain, Jai G. Broome, Ming-Huei Chen, Florian Thibord, Caitlin Mchugh, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing from NHLBI's Trans-Omics for Precision Medicine Initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet …

Investigating Gene-Environment Interaction In A Double-Hit Model For Autism Spectrum Disorder, Melvin Maroon

Undergraduate Student Research Internships Conference

With the exponential advancements seen in the field of sequencing technology, the science community has come to identify hundreds of potential genetic risk factors for neuropsychiatric disorders. Despite our knowledge that such risk factors exist, we have yet to understand their specific influences on the behavioral profile of an individual. In addition, maternal infection during pregnancy can have longstanding detrimental outcomes on a child’s development. This is especially impactful with the present threat of viral infection during the pandemic. Our study aims to understand the influence of a specific genetic and environmental factor on a preclinical rodent model’s behavioral development. …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Mayer Rokitansky Kuster Hauser Syndrome: A Case Of Mullerian Agenesis, Anu Baby, Simi Kurian, Rani Jose

Manipal Journal of Nursing and Health Sciences

Developmental anomalies of the Mullerian duct are one of the fascinating congenital disorders encountered in which Mayer Rokitansky Kuster Hauser syndrome (MRKH) is one of the wide variety of malformations. The most common presentation in MRKH syndrome is primary amenorrhea with normal development of secondary sexual characteristics and normal female karyotype (46, XX). The ovaries and fallopian tubes are usually functional, but the uterus and upper two-third vagina are either underdeveloped or absent. MRKH syndrome can either be an isolated utero-vaginal aplasia (Type I) or associated with extragenital anomalies (Type II). A case of Type I MRKH syndrome is reported …

Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse

Publications and Research

Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which …

Genome Sequencing Unveils A Regulatory Landscape Of Platelet Reactivity, Ali R. Keramati, Ming-Huei Chen, Lisa R. Yanek, Arunoday Bhan, John Blangero, Benjamin A. T. Rodriguez, Joanne E. Curran, Michael Mahaney, Harald Hh Goring, Ravi Duggirala

School of Medicine Publications and Presentations

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are …

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 …

Replication Protein A (Rpa) Targeting Of Uracil Dna Glycosylase (Ung2), Derek Chen, Brian P Weiser

Rowan-Virtua Research Day

Replication Protein A (RPA) is a single stranded DNA binding protein which stabilizes ssDNA for replication and repair. One function of RPA is to bind the DNA repair enzyme uracil DNA glycosylase (UNG2) and direct its activity towards ssDNA dsDNA junctions.

UNG2 removes uracil bases from DNA which can appear through dUMP misincorporation or through cytosine deamination. If uracil is present instead of a cytosine, then the original GC pair becomes a GU pair. The uracil will then base pair to adenine in the replicated daughter strand. This results in a GC → AT mutation that could contribute to cancer …

Delineating The Upc2a Regulon In Candida Glabrata, Yu Li

Theses and Dissertations (ETD)

Candida glabrata is the second most common cause of invasive candidiasis. Intrinsic resistance has greatly limited the utility of the triazole antifungal, fluconazole, in the treatment of invasive fungal infection. The transcription factor Upc2 regulates the expression of sterol biosynthesis genes in yeast. Disrupting UPC2A in C. glabrata greatly increases its susceptibility to fluconazole (FLU) in both FLU-susceptible and -resistant clinical isolates. Therefore, the Upc2A and its target genes represent a potential pathway for overcoming FLU resistance in C. glabrata. We aimed to delineate the Upc2A regulon to determine its target genes involved in FLU resistance. Transcriptome sequencing (RNA-seq) analysis …

Muc13 Enhances Colorectal Cancer Metastasis, Kyle Doxtater

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are …

Genetic Correlates In Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated With Hyper-Cvad/Hyper-Cmad Plus Dasatinib Or Hyper-Cvad Plus Ponatinib, Yuya Sasaki Md, Phd, Hagop Kantarjian Md, Nicholas J. Short Md, Farhad Ravandi Md, Marina Konopleva Md, Phd, Guillermo Garcia-Manero Md, Pandrew Futreal Phd, Feng Wang, Koichi Takahashi Md, Phd, Elias Jabbour Md

2021 Education Week Posters

Department of Leukemia Research

Department of Leukemia

Department of Genomic Medicine

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Living With It: A Patient’S And A Biochemist’S Perspective On Kidney Disease; A Historical Review Of Alport Syndrome, Jacob Olson

WWU Honors College Senior Projects

A review paper on the origin of health studies around Alport Syndrome, including aspects of genetics, pharmacy, and biochemistry, from the past to today and beyond. This report deals with important aspects of health development with regards to kidney disease overall, but narrows its focus on Alport Syndrome specifically due to the personal nature of the topic for the author. While this paper includes no personal testimony, as it is strictly meant to be formal, the author shares a deep connection with the material.