Genetics and Genomics Commons^™

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Population Genetic Diversity In Two Biological Systems, Alyson Emery

Electronic Theses and Dissertations

Population genetic analysis can be used to answer questions about population structure and composition in many biological systems. Recent improvements to sequencing technologies have made population genetic studies more accessible than ever before. Many of the same techniques can be applied to different biological systems, but some analyses may differ depending on how genetically divergent the populations in question are. Here, we describe two unique projects using next-generation genome sequencing, each looking at population structure at different levels of genetic divergence: the first involved determining interspecific population structure between two species of hybridizing field cricket using a novel sequencing method, …

Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown

Electronic Theses and Dissertations

The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …

Technical Note: Assessing Gps Sensor Accuracy Using Real-Time Kinematic Device For Livestock Tracking, Biquan Zhao, Rebecca Mcdermott, Galen E. Erickson, Yijie Xiong

Department of Animal Science: Faculty Publications

The technical aspects of global positioning system (GPS) sensors have been improved substantially over the years, making them valuable and popular tools for livestock tracking. Using GPS sensors allows producers and researchers to locate grazing livestock, monitor their behavior and distribution, and gather referencing information about the health status of the animals and pastures. However, interpreting the behavior of grazing livestock, such as cattle, from GPS data can be difficult due to positioning inaccuracies. Without knowing the positioning accuracy range of GPS sensors, achieving high-level confidence in determining grazing densities and identifying abnormal livestock movement patterns is challenging. …

Forest Defoliation By And Invasive Outbreak Insect: Catastrophic Consequences For A Charismatic Mega Moth, Richard L. Lindroth, Mark R. Zierden, Clay J. Morrow, Patricia C. Fernandez

Aspen Bibliography

Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage-induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4-fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and …

Perspectives From Caregivers For Children With Retinoblastoma: Psychosocial Concerns And Genetic Counseling, Kayla Marie Lashinger

Theses and Dissertations

Caregivers play a vital role in the care of children affected with retinoblastoma as most cases are diagnosed before the age of five years old. While previous studies have explored the psychosocial needs of caregivers of children with pediatric cancer, these have not specifically focused on retinoblastoma in the United States (US). Prior research identified the profound emotional burden in terms of depression, anxiety, guilt, isolation, and loneliness experienced by caregivers. Given previous findings and the National Cancer Institute’s recommendation for genetic counseling and testing for all individuals affected with retinoblastoma, this study aimed to assess psychosocial concerns in relation …

Preimplantation Genetic Testing For Sickle Cell Disease; Exploring The Effect Health Disparities Have On Parental Awareness And Interest, Justine Frances Manigault

Theses and Dissertations

Sickle cell disease (SCD) is a group of disorders of the hemoglobin resulting in episodes of chronic pain, pulmonary hypertension, progressive multiorgan damage, risk for stroke, and increased mortality. It is caused by biallelic pathogenic variants in the HBB gene and 1 in 12 African Americans, 1 in 100 Hispanic individuals, and 1 in 30-50 Mediterranean people are reported to be carriers of the disease and have sickle cell trait (SCT). SCD is typically diagnosed through newborn screening; however, when prospective parents are aware of their carrier status, they can conceive via in vitro fertilization (IVF) and have genetic testing …

The Autistic Adult's Perspective On Genetic Testing In The Prenatal And Cancer Settings, Robin Lisa Urban

Theses and Dissertations

Prenatal and cancer genetic tests are recommended by many professional medical organizations. Previous studies have shown that autistic adults have a negative opinion towards genetic testing for autism but have not explored if this sentiment is shared for other types of genetic testing. We used a descriptive, web-based survey of autistic adults to assess their attitudes towards prenatal and cancer genetic testing (n=36). Our data showed that overall attitudes towards prenatal and cancer genetic testing are positive. Notably, participants had slightly more positive attitudes towards prenatal genetic testing related to neurodevelopmental disorders when compared to testing for disorders primarily affecting …

Perspectives On Transition To Adult Healthcare For Adults With Williams Syndrome And Their Caregivers, Andrea Johnson

Theses and Dissertations

Transitioning to adult care services is a crucial time for young adults with a genetic condition. Many of these conditions are diagnosed early in childhood, with follow-up care fragmented and dependent on the specific needs of the individual. Williams syndrome (WS) is a complex genetic condition characterized by multisystemic features. The variation in the clinical presentation of adults with WS can influence the individual’s ability to transition from pediatric care because of its medical complications, variable and poorly characterized psychiatric needs, and intellectual disability that causes difficulty communicating health-related needs to providers. This study focused on understanding the needs of …

Assessing Obgyn Residents’ Knowledge, Attitudes, And Current Practices For Carrier Screening, Aubrey Morgan Surian

Theses and Dissertations

Obstetricians and gynecologists (OBGYNs) are the main providers that order carrier screening on a regular basis, so it is important to understand their knowledge, attitudes, and current practices regarding this screening. There are two primary professional organizations that have established practice guidelines for carrier screening, the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG). With the growth of pan-ethnic carrier screening, these guidelines have become remarkably different. This study aimed to assess resident OBGYN’s utilization of pan-ethnic carrier screening, discern any discrepancies between knowledge, attitudes, and current practices, identify possible practice resources that may …

Perception Of Alzheimer’S Actionability Among End Users Of Direct-To-Consumer Genetic Tests, Emily Mason

Theses and Dissertations

The APOE ε4 allele is the best-known genetic risk factor for developing late-onset Alzheimer’s disease. Although new evidence is emerging, the extent to which lifestyle improvements can reduce Alzheimer’s risk needs further investigation. Research suggests that individuals with a higher genetic risk may be more likely to engage in risk-reducing health behavior changes following results disclosure. This study aimed to better understand these findings by assessing the health behavior and perceptions of Alzheimer’s actionability among consumers of DTC genetic tests. Our study revealed that individuals with 2 copies of the APOE ε4 allele were less likely to make lifestyle modifications …

Patients’ Experience Of Care Following Perinatal Case Conference, Mary Elise Nolen

Theses and Dissertations

The Perinatal Case Conference (PCC) at Prisma Health-Midlands Maternal-Fetal Medicine (MFM) is a biweekly multidisciplinary meeting to discuss pregnancies with prenatally identified congenital anomalies. Patients are primarily cared for by MFM and may have appointments with various subspecialists during their pregnancy. The goals of the PCC are multidisciplinary collaboration in planning for the management of each pregnancy and familiarizing each practitioner with the pending cases, so if or when intervention is needed, the clinicians are familiar with the case.

Researchers performed a chart review and surveyed patients whose pregnancies were discussed in the PCC to learn the patient’s perspective of …

The Utility Of Referrals From A State Early Intervention System To A Pediatric Genetics Clinic To Increase Access To Genetic Services, Mikayla Jennings

Theses and Dissertations

Infants or toddlers enrolled in state early intervention programs have developmental delays or are diagnosed with conditions that may result in developmental delays. These infants receive a wide range of services from early intervention. In the state of South Carolina, children in the early intervention program are offered genetic evaluations at no cost to the family. Exploring the relationship between state early intervention systems and genetic clinics and the impact on this particular patient population can provide support for new and continued use of this service delivery model.

The purpose of this study was to evaluate the service delivery model …

Cancer Screening For Patients With Intellectual Disability: Exploring Parent And Caregiver Perspectives, Jennifer Ryan

Theses and Dissertations

Intellectual disability (ID) is defined as a combination of deficits in cognitive and adaptive function, both of which must be present early in life. Adults with ID frequently have unique healthcare needs; however, they also require care that is routine for all adults. This includes cancer screening. The goal of this study was to evaluate whether or not adults with ID are undergoing cancer screening, understand the barriers they have faced in obtaining screening, and collect recommendations from parents and caregivers on ways to improve access to and facilitate screening for this population. We surveyed parents and caregivers of adults …

Neuromodulatory Co-Expression In Cardiac Vagal Motor Neurons Of The Dorsal Motor Nucleus Of The Vagus, Eden Hornung, Shaina Robbins, Ankita Srivastava, Sirisha Achanta, Jin Chen, Zixi Jack Cheng, James Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Vagal innervation is well known to be crucial to the maintenance of cardiac health, and to protect and recover the heart from injury. Only recently has this role been shown to depend on the activity of the underappreciated dorsal motor nucleus of the vagus (DMV). By combining neural tracing, transcriptomics, and anatomical mapping in male and female Sprague-Dawley rats, we characterize cardiac-specific neuronal phenotypes in the DMV. We find that the DMV cardiac-projecting neurons differentially express pituitary adenylate cyclase-activating polypeptide (PACAP), cocaine- and amphetamine-regulated transcript (CART), and synucleins, as well as evidence that they participate in neuromodulatory co-expression involving catecholamines. …

Investigation Of P27 Tumor Suppressor Gene (Cdkn1b) Polymorphisms In Dogs With Malignant Mammary Tumors, Gizem Kırmızıoğlu, Iraz Akış

The Thai Journal of Veterinary Medicine

Mammary tumors are the most common neoplasm in dogs, with a high mortality rate. The development of canine mammary tumors (CMT) is multifactorial, but different incidence rates between breeds suggest the effects of genetic risk factors. Many CMT-associated candidate genes were reported, mainly involved in cell cycle control. This study aims to investigate p27 tumor suppressor gene polymorphisms in dogs with mammary tumors and analyze the association between variations and CMTs. For this purpose, case and control groups were formed from 22 dogs diagnosed with malignant mammary tumors and 10 dogs with healthy mammary glands. The whole canine p27 gene …

Knockdown Of Gonadotropin-Releasing Hormone Ii Receptor Impairs Ovulation Rate, Corpus Luteum Development, And Progesterone Production In Gilts, Amy T. Desaulniers, Rebecca Cederberg, Clay A. Lents, Brett White

Department of Animal Science: Faculty Publications

Reproduction is classically controlled by gonadotropin-releasing hormone (GnRH-I) and its receptor (GnRHR-I) within the brain. In pigs, a second form (GnRH-II) and its specific receptor (GnRHR-II) are also produced, with greater abundance in peripheral vs. central reproductive tissues. The binding of GnRH-II to GnRHR-II has been implicated in the autocrine/paracrine regulation of gonadal steroidogenesis rather than gonadotropin secretion. Blood samples were collected from transgenic gilts, with the ubiquitous knockdown of GnRHR-II (GnRHR-II KD; n = 8) and littermate controls (n = 7) at the onset of estrus (follicular) and 10 days later (luteal); serum concentrations of 16 steroid hormones …

Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc

Computational Medicine Center Faculty Papers

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1-7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to …

Alternate Conformational Trajectories In Ribosome Translocation, Jose L. Alejo, Dylan Girodat, Michael J. Hammerling, Jessica A. Willi, Michael C. Jewett, Aaron E. Engelhardt, Katarzyna P. Adamala

Chemistry & Biochemistry Faculty Publications and Presentations

Abstract

Translocation in protein synthesis entails the efficient and accurate movement of the mRNA-[tRNA]₂ substrate through the ribosome after peptide bond formation. An essential conformational change during this process is the swiveling of the small subunit head domain about two rRNA ‘hinge’ elements. Using iterative selection and molecular dynamics simulations, we derive alternate hinge elements capable of translocation in vitro and in vivo and describe their effects on the conformational trajectory of the EF-G-bound, translocating ribosome. In these alternate conformational pathways, we observe a diversity of swivel kinetics, hinge motions, three-dimensional head domain trajectories and tRNA dynamics. By finding …