Medical Sciences Commons^™

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling, Ji Ye Lim, Eunju Kim, Collin M Douglas, Marvin Wirianto, Chorong Han, Kaori Ono, Sun Young Kim, Justin H Ji, Celia K Tran, Zheng Chen, Karyn A Esser, Seung-Hee Yoo

Journal Articles

Numerous molecular and physiological processes in the skeletal muscle undergo circadian time-dependent oscillations in accordance with daily activity/rest cycles. The circadian regulatory mechanisms underlying these cyclic processes, especially at the post-transcriptional level, are not well defined. Previously, we reported that the circadian E3 ligase FBXL21 mediates rhythmic degradation of the sarcomere protein TCAP in conjunction with GSK-3β, and Psttm mice harboring an Fbxl21 hypomorph allele show reduced muscle fiber diameter and impaired muscle function. To further elucidate the regulatory function of FBXL21 in skeletal muscle, we investigated another sarcomere protein, Myozenin1 (MYOZ1), that we identified as an FBXL21-binding protein from …

North American Genetic Counselors' Approach To Collecting And Using Ancestry In Clinical Practice, Alexandra Hubbel, Elizabeth Hogan, Anne Matthews, Aaron Goldenberg

Student Scholarship

Current guidelines from the National Society of Genetic Counselors (NSGC) recommend that patients' ancestry be obtained when taking a family history. However, no study has explored how consistently genetic counselors obtain or utilize this information. The goals of this study included assessing how genetic counselors collect their patients' ancestry, what factors influence this decision, and how they view the utility of this information. Genetic counselors working in a direct patient care setting in the US or Canada were recruited to participate in an anonymous survey via an NSGC email blast. Most participants (n = 115) obtain information about their patients' …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Journal Articles

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

Shared Brain And Genetic Architectures Between Mental Health And Physical Activity, Wei Zhang, Sarah E. Paul, Anderson M. Winkler, Ryan Bogdan, Janine D. Bijsterbosch

School of Medicine Publications and Presentations

Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear. Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (N = 6389), we applied canonical correlation analysis to estimate associations between the amplitude and connectivity strength of subnetworks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health measures (primarily of depression, anxiety …

Interplay: The Essential Role Between Insm1 And N-Myc In Aggressive Neuroblastoma, Chiachen Chen, Michael S. Lan

School of Medicine Faculty Publications

An aggressive form of neuroblastoma (NB), a malignant childhood cancer derived from granule neuron precursors and sympathoadrenal lineage, frequently comprises MYCN amplification/elevated N-Myc expression, which contributes to the development of neural crest-derived embryonal malignancy. N-Myc is an oncogenic driver in NB. Persistent N-Myc expression during the maturation of SA precursor cells can cause blockage of the apoptosis and induce abnormal proliferation, resulting in NB development. An insulinoma-associated-1 (INSM1) zinc-finger transcription factor has emerged as an NB biomarker that plays a critical role in facilitating tumor cell growth and transformation. INSM1 plays an essential role in sympathoadrenal cell differentiation. N-Myc activates …

The Genetic Contribution To Solving The Cocktail-Party Problem, Samuel R. Mathias, Emma Knowles, Josephine Mollon, Amanda Rodrigue, Mary K. Woolsey, Rene L. Olvera, Juan M. Peralta, Satish Kumar, Harald H. H. Goring, Ravi Duggirala, Joanne E. Curran, John Blangero, David C. Glahn

School of Medicine Publications and Presentations

Communicating in everyday situations requires solving the cocktail-party problem, or segregating the acoustic mixture into its constituent sounds and attending to those of most interest. Humans show dramatic variation in this ability, leading some to experience real-world problems irrespective of whether they meet criteria for clinical hearing loss. Here, we estimated the genetic contribution to cocktail-party listening by measuring speech-reception thresholds (SRTs) in 425 people from large families and ranging in age from 18 to 91 years. Roughly half the variance of SRTs was explained by genes (h 2 = 0.567). The genetic correlation between SRTs and hearing thresholds …

Metabolomics In Pulmonary Medicine: Extracting The Most From Your Data, Stacey N. Reinke, Romanas Chaleckis, Craig E. Wheelock

Research outputs 2022 to 2026

The metabolome enables unprecedented insight into biochemistry, providing an integrated signature of the genome, transcriptome, proteome and exposome. Measurement requires rigorous protocols combined with specialised data analysis to achieve its promise.

A Genome-Wide Screen Identifies Pdpk1 As A Target To Enhance The Efficacy Of Mek1/2 Inhibitors, Weijia Cai, Nicole A. Wilski, Timothy J. Purwin, Megane Vernon, Manoela Tiago, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Melanomas frequently harbor activating NRAS mutations. However, limited advance has been made in developing targeted therapy options for NRAS mutant melanoma patients. MEK inhibitors (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of Phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacological and molecular approaches. Combined PDPK1 inhibitors (PDPK1i) with MEKi suppressed NRAS mutant xenograft growth and induced gasdermin E-associated pyroptosis. In an immune-competent …

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Journal Articles

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Acylcarnitines And Genetic Variation In Fat Oxidation Genes In Hiv-Infected, Antiretroviral-Treated Children With And Without Myopathy, Brian Kirmse, Charlotte Hobbs, Lisa Aaron, Grace Montepiedra, Marshall Summar, Paige L Williams, Caitlin J Smith, Russell Van Dyke, Chunli Yu, Kelli K Ryckman, William Borkowsky

Journal Articles

BACKGROUND: Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

METHODS: Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

RESULTS: Abnormal ACP …

Lower Sars-Cov-2 Seroprevalence Among Cancer Patients In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, John R. Ngowi, Phoebe B. Peña, Ashley A. Clegg, Owen Ngalamika, Chacha J. Mwita, Julius Mwaiselage, Charles Wood

School of Medicine Faculty Publications

Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and …

Structural Basis For The Simultaneous Recognition Of Nemo And Acceptor Ubiquitin By The Hoip Nzf1 Domain, Simin Rahighi, Mamta Iyer, Hamid Oveisi, Sammy Nasser, Vincent Duong

Pharmacy Faculty Articles and Research

Ubiquitination of NEMO by the linear ubiquitin chain assembly complex (LUBAC) is essential for activating the canonical NF-κB signaling pathway. While the NZF1 domain of the HOIP subunit of LUBAC recognizes the NEMO substrate, it is unclear how it cooperates with the catalytic domains in the ubiquitination process. Here, we report a crystal structure of NEMO in complex with HOIP NZF1 and linear diubiquitin chains, in which the two proteins bind to distinct sites on NEMO. Moreover, the NZF1 domain simultaneously interacts with NEMO and Ile44 surface of a proximal ubiquitin from a linear diubiquitin chain, where the C-term tail …

Identification Of Healthspan-Promoting Genes In Caenorhabditis Elegans Based On A Human Gwas Study, Nadine Saul, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik Von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten

School of Medicine Publications and Presentations

To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Myles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication …

Epigenetic Mechanisms Influencing Therapeutic Response In Breast Cancer., Amaia Arruabarrena-Aristorena, Eneda Toska

Kimmel Cancer Center Faculty Papers

The majority of breast cancers are estrogen receptor (ER)+ and agents targeting the ER signaling pathway have markedly increased survival for women with breast cancer for decades. However, therapeutic resistance eventually emerges, especially in the metastatic setting. In the past decade disrupted epigenetic regulatory processes have emerged as major contributors to carcinogenesis in many cancer types. Aberrations in chromatin modifiers and transcription factors have also been recognized as mediators of breast cancer development and therapeutic outcome, and new epigenetic-based therapies in combination with targeted therapies have been proposed. Here we will discuss recent progress in our understanding of the chromatin-based …

Genomic Answers For Children: Dynamic Analyses Of >1000 Pediatric Rare Disease Genomes., Ana S A Cohen, Emily G. Farrow, Ahmed Abdelmoity, Joseph Alaimo, Shivarajan Manickavasagam Amudhavalli, John Anderson, Lalit R. Bansal, Lauren E. Bartik, Primo Baybayan, Bradley Belden, Courtney D. Berrios, Rebecca L. Biswell, Pawel Buczkowicz, Orion Buske, Shreyasee Chakraborty, Warren A. Cheung, Keith A. Coffman, Ashley M. Cooper, Laura A. Cross, Tom Curran, Thuy Tien T. Dang, Mary M. Elfrink, Kendra Engleman, Erin Day Fecske, Cynthia Fieser, Keely M. Fitzgerald, Emily Fleming, Randi N. Gadea, Jennifer L. Gannon, Rose N. Gelineau-Morel, Margaret Gibson, Jeffrey Goldstein, Elin Grundberg, Kelsee Halpin, Brian S. Harvey, Bryce Heese, Wendy Hein, Suzanne M. Herd, Susan Starling Hughes, Mohammed Ilyas, Jill Jacobson, Janda L. Jenkins, Shao Jiang, Jeffrey J. Johnston, Kathryn Keeler, Jonas Korlach, Jennifer Kussman, Christine Lambert, Caitlin E. Lawson, Jean-Baptist Lepichon, J Steven Leeder, Vicki C. Little, Daniel A. Louiselle, Michael Lypka, Brittany D. Mcdonald, Neil Miller, Ann Modrcin, Annapoorna Nair, Shelby H. Neal, Christopher M. Oermann, Donna M. Pacicca, Kailash Pawar, Nyshele L. Posey, Nigel Price, Laura M B Puckett, Julio Quezada, Nikita Raje, William J. Rowell, Eric T. Rush, Venkatesh Sampath, Carol J. Saunders, Caitlin Schwager, Richard M. Schwend, Elizabeth Shaffer, Craig Smail, Sarah E. Soden, Meghan Strenk, Bonnie Sullivan, Brooke Sweeney, Jade B. Tam-Williams, Adam Walter, Holly Welsh, Aaron M. Wenger, Laurel K. Willig, Yun Yan, Scott T. Younger, Dihong Zhou, Tricia N. Zion, Isabelle Thiffault, Tomi Pastinen

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program.

METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes.

RESULTS: Diagnostic rates ranged from 11% in patients with prior negative …

Natural Killer Cells In Liver Transplantation: Can We Harness The Power Of The Immune Checkpoint To Promote Tolerance?, Jennifer Halma, Stephen Pierce, Rebecca Mclennan, Todd Bradley, Ryan T. Fischer

Manuscripts, Articles, Book Chapters and Other Papers

The roles that natural killer (NK) cells play in liver disease and transplantation remain ill-defined. Reports on the matter are often contradictory, and the mechanisms elucidated are complex and dependent on the context of the model tested. Moreover, NK cell attributes, such as receptor protein expression and function differ among species, make study of primate or rodent transplant models challenging. Recent insights into NK function and NK-mediated therapy in the context of cancer therapy may prove applicable to transplantation. Of specific interest are immune checkpoint molecules and the mechanisms by which they modulate NK cells in the tumor micro-environment. In …

Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li

Department of Medicine Faculty Papers

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy …

A Patient-Derived Ipsc Model To Study Glutamate Deficiency By Shank-3 Mutation In Autism Spectrum Disorder, Tiffany Berry, Courtney Caccia

Biology Student Scholarship

Tiffany Berry ’22, Majors: Biology and Psychology

Courtney Caccia ’22, Majors: Biology and Psychology

Faculty Mentor: Dr. Charles Toth, Biology

The use of human stem cell lines derived from persons with Autism Spectrum Disorder (ASD) provides a unique opportunity to model brain growth and potential to regain brain activity for treatment. Our lab has previously used stem cells to derive 3D cardiomyocytes to examine cardiovascular disease as well as kidney organoids and macrophages to study kidney disease. Using techniques our lab has learned using these stem cell models have prepared us to examine cell communication in mutated neurons. We will …

Epigenetic Pathogenesis Of Neurological Disorders In Utero And Considerations For Genetic Counseling, Lauren Juga

Senior Honors Theses

Epigenetic modifications are a major focus of study in the pathogenesis of many disorders regarding metabolism, aging, neurodevelopment, and neurodegeneration. Epigenetic mechanisms are present throughout life but are especially vital to guiding fetal development. The precise timing of gene activation and deactivation guides stem cell differentiation through each embryonic stage. After exposure to environmental stimuli, gene expression can be altered by transcription factors, resulting in observable phenotypes and even pathology. Here, the epigenetic mechanisms responsible for the pathogenesis of neurodevelopmental and neuropsychiatric disorders are explored in response to environmental perturbations in utero. The present goal is to identify correlations between …

Landscape Of Molecular Crosstalk Perturbation Between Lung Cancer And Covid-19, Aditi Kuchi, Jiande Wu, Jyotsna Fuloria, Chindo Hicks

School of Medicine Faculty Publications

Background: Lung cancer patients have the worst outcomes when affected by coronavirus disease 2019 (COVID-19). The molecular mechanisms underlying the association between lung cancer and COVID-19 remain unknown. The objective of this investigation was to determine whether there is crosstalk in molecular perturbation between COVID-19 and lung cancer, and to identify a molecular signature, molecular networks and signaling pathways shared by the two diseases. Methods: We analyzed publicly available gene expression data from 52 severely affected COVID-19 human lung samples, 594 lung tumor samples and 54 normal disease-free lung samples. We performed network and pathways analysis to identify molecular networks …

Molecular Diagnoses Of X-Linked And Other Genetic Hypophosphatemias: Results From A Sponsored Genetic Testing Program., Eric T. Rush, Britt Johnson, Swaroop Aradhya, Daniel Beltran, Sara L. Bristow, Scott Eisenbeis, Norma E. Guerra, Stan Krolczyk, Nicole Miller, Ana Morales, Prameela Ramesan, Soodabeh Sarafrazi, Rebecca Truty, Kathryn Dahir

Manuscripts, Articles, Book Chapters and Other Papers

X-linked hypophosphatemia (XLH), a dominant disorder caused by pathogenic variants in the PHEX gene, affects both sexes of all ages and results in elevated serum fibroblast growth factor 23 (FGF23) and below-normal serum phosphate. In XLH, rickets, osteomalacia, short stature, and lower limb deformity may be present with muscle pain and/or weakness/fatigue, bone pain, joint pain/stiffness, hearing difficulty, enthesopathy, osteoarthritis, and dental abscesses. Invitae and Ultragenyx collaborated to provide a no-charge sponsored testing program using a 13-gene next-generation sequencing panel to confirm clinical XLH or aid diagnosis of suspected XLH/other genetic hypophosphatemia. Individuals aged ≥6 months with clinical XLH or …

Using Crispr Gene Editing To Prevent Accumulation Of Lipids In Hepatocytes, Erin Young, Cem Kuscu, Christine Watkins, Murat Dogan

Longitudinal Scholar's Project

CRISPR gene editing is a molecular technology that can be used to silence gene expression. In this experiment, genes that are known to play a role in lipid accumulation in hepatocytes were targeted. Specifically, levels of fatty acid transport proteins 2 and 5 (FATP2 & 5) have been shown to be elevated in cases of non-alcoholic fatty liver disease. The goal of this experiment was to reduce expression of these genes by using a dead Cas9 (dCas9) protein with an attached inhibitory domain (KRAB) that acts on the promotor region. When measuring the mRNA expression, it was determined that the …

Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

BACKGROUND: Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

METHODS: In this article, we discuss how application of standard theoretical null distributional assumptions …

Extracellular Mechanotransduction, Stephen J. Haller, Andrew T. Dudley

Journal Articles: Genetics, Cell Biology & Anatomy

We highlight the force-sensing function of extracellular matrix and present a complementary mechanotransduction paradigm.

Mintruls: Prediction Of Mirna-Mrna Target Site Interactions Using Regularized Least Square Method, Sushil Kumar Shakyawar, Siddesh Southekal, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Identification of miRNA-mRNA interactions is critical to understand the new paradigms in gene regulation. Existing methods show suboptimal performance owing to inappropriate feature selection and limited integration of intuitive biological features of both miRNAs and mRNAs. The present regularized least square-based method, mintRULS, employs features of miRNAs and their target sites using pairwise similarity metrics based on free energy, sequence and repeat identities, and target site accessibility to predict miRNA-target site interactions. We hypothesized that miRNAs sharing similar structural and functional features are more likely to target the same mRNA, and conversely, mRNAs with similar features can be targeted by …

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

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 …