Medicine and Health Sciences Commons^™

Diagnostic Accuracy Of Macular Thickness Map And Texture En Face Images For Detecting Glaucoma In Eyes With Axial High Myopia, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Mark Christopher, Leslie Hyman, Jost B Jonas, Robert N Weinreb, Linda M Zangwill

Wills Eye Hospital Papers

Purpose: To evaluate the diagnostic accuracy of a novel optical coherence tomography texture-based en face image analysis (SALSA-Texture) that requires segmentation of only 1 retinal layer for glaucoma detection in eyes with axial high myopia, and to compare SALSA-Texture with standard macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fiber layer (mRNFL) thickness, and ganglion cell complex (GCC) thickness maps.

Design: Comparison of diagnostic approaches.

Methods: Cross-sectional data were collected from 92 eyes with primary open-angle glaucoma (POAG) and 44 healthy control eyes with axial high myopia (axial length >26 mm). Optical coherence tomography texture en face images, …

Three-Dimensional Structure Of Human Cyclooxygenase (Hcox)-1., Morena Miciaccia, Benny Danilo Belviso, Mariaclara Iaselli, Gino Cingolani, Savina Ferorelli, Marianna Cappellari, Paola Loguercio Polosa, Maria Grazia Perrone, Rocco Caliandro, Antonio Scilimati

Department of Biochemistry and Molecular Biology Faculty Papers

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined …

Machine Learning Approaches Identify Genes Containing Spatial Information From Single-Cell Transcriptomics Data., Phillipe Loher, Nestoras Karathanasis

Computational Medicine Center Faculty Papers

The development of single-cell sequencing technologies has allowed researchers to gain important new knowledge about the expression profile of genes in thousands of individual cells of a model organism or tissue. A common disadvantage of this technology is the loss of the three-dimensional (3-D) structure of the cells. Consequently, the Dialogue on Reverse Engineering Assessment and Methods (DREAM) organized the Single-Cell Transcriptomics Challenge, in which we participated, with the aim to address the following two problems: (a) to identify the top 60, 40, and 20 genes of the Drosophila melanogaster embryo that contain the most spatial information and (b) to …

Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global …

Discoidin Domain Receptor 1 Functionally Interacts With The Igf-I System In Bladder Cancer, Simone Buraschi, Alaide Morcavallo, Thomas Neill, Manuela Stefanello, Chiara Palladino, Shi-Qiong Xu, Antonino Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Brief Communication: Long-Term Absence Of Langerhans Cells Alters The Gene Expression Profile Of Keratinocytes And Dendritic Epidermal T Cells., Qingtai Su, Aurélie Bouteau, Jacob Cardenas, Balaji Uthra, Yuanyaun Wang, Cynthia Smitherman, Jinghua Gu, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells' biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active …

Optimizing Clinical And Cost Outcomes For Patients On Enteral Nutrition Support For Treatment Of Exocrine Pancreatic Insufficiency: Proceedings From An Expert Advisory Board Meeting, Joseph I. Boullata, Janice L. Clarke, Archie Stone, Alexis Skoufalos, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Highly Efficient 5' Capping Of Mitochondrial Rna With Nad+ And Nadh By Yeast And Human Mitochondrial Rna Polymerase, Jeremy G Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Atif Towheed, Douglas C. Wallace, Megerditch Kiledjian, Dmitry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels

Department of Biochemistry and Molecular Biology Faculty Papers

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter …

Saturation Mutagenesis Reveals Manifold Determinants Of Exon Definition., Shengdong Ke, Vincent Anquetil, Jorge Rojas Zamalloa, Alisha Maity, Anthony Yang, Mauricio A. Arias, Sergey Kalachikov, James J Russo, Jingyue Ju, Lawrence A. Chasin

Student Papers, Posters & Projects

To illuminate the extent and roles of exonic sequences in the splicing of human RNA transcripts, we conducted saturation mutagenesis of a 51-nt internal exon in a three-exon minigene. All possible single and tandem dinucleotide substitutions were surveyed. Using high-throughput genetics, 5560 minigene molecules were assayed for splicing in human HEK293 cells. Up to 70% of mutations produced substantial (greater than twofold) phenotypes of either increased or decreased splicing. Of all predicted secondary structural elements, only a single 15-nt stem-loop showed a strong correlation with splicing, acting negatively. The in vitro formation of exon-protein complexes between the mutant molecules and …

Negative Regulation Of Urokinase Receptor Activity By A Gpi-Specific Phospholipase C In Breast Cancer Cells., Michiel Van Veen, Elisa Matas-Rico, Koen Van De Wetering, Daniela Leyton-Puig, Katarzyna M. Kedziora, Valentina De Lorenzi, Yvette Stijf-Bultsma, Bram Van Den Broek, Kees Jalink, Nicolai Sidenius, Anastassis Perrakis, Wouter H. Moolenaar

Department of Dermatology and Cutaneous Biology Faculty Papers

The urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein that promotes tissue remodeling, tumor cell adhesion, migration and invasion. uPAR mediates degradation of the extracellular matrix through protease recruitment and enhances cell adhesion, migration and signaling through vitronectin binding and interactions with integrins. Full-length uPAR is released from the cell surface, but the mechanism and significance of uPAR shedding remain obscure. Here we identify transmembrane glycerophosphodiesterase GDE3 as a GPI-specific phospholipase C that cleaves and releases uPAR with consequent loss of function, whereas its homologue GDE2 fails to attack uPAR. GDE3 overexpression depletes uPAR from distinct basolateral membrane domains in …

A Cost-Reducing Extracorporeal Membrane Oxygenation (Ecmo) Program Model: A Single Institution Experience., Nicholas C. Cavarocchi, S Wallace, E Y. Hong, A Tropea, J Byrne, Harrsion Pitcher, Hitoshi Hirose

Department of Surgery Faculty Papers

BACKGROUND: The worldwide demand for ECMO support has grown. Its provision remains limited due to several factors (high cost, complicated technology, lack of expertise) that increase healthcare cost. Our goal was to assess if an intensive care unit (ICU)-run ECMO model without continuous bedside perfusionists would decrease costs while maintaining patient safety and outcomes.

METHOD: A new ECMO program was implemented in 2010, consisting of dedicated ICU multidisciplinary providers (ICU-registered nurses, mid-level providers and intensivists). In year one, we introduced an education platform, new technology and dedicated space. In year two, continuous bedside monitoring by perfusionists was removed and new …

Architecture Of Viral Genome-Delivery Molecular Machines., Anshul Bhardwaj, Adam S. Olia, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

From the abyss of the ocean to the human gut, bacterial viruses (or bacteriophages) have colonized all ecosystems of the planet earth and evolved in sync with their bacterial hosts. Over 95% of bacteriophages have a tail that varies greatly in length and complexity. The tail complex interrupts the icosahedral capsid symmetry and provides both an entry for viral genome-packaging during replication and an exit for genome-ejection during infection. Here, we review recent progress in deciphering the structure, assembly and conformational dynamics of viral genome-delivery tail machines. We focus on the bacteriophages P22 and T7, two well-studied members of the …

Therapeutic Implications Of Estrogen For Cerebral Vasospasm And Delayed Cerebral Ischemia Induced By Aneurysmal Subarachnoid Hemorrhage., Dale Ding, Robert M Starke, Aaron S Dumont, Gary K Owens, David M Hasan, Nohra Chalouhi, Md, Ricky Medel, Chih-Lung Lin

Department of Neurosurgery Faculty Papers

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 β -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal …

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …

Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …

We Can Do It Together: Par1/Par2 Heterodimer Signaling In Vsmcs., Rafal Pawlinski, Michael Holinstat

Department of Medicine Faculty Papers

In this issue, Sevigny and colleagues demonstrate that a protease-activated receptor 1 (PAR1)-PAR2 heterodimer regulates vascular smooth muscle cell (VSMC) hyperplasia following vascular injury ¹. PARs belong to a family of G-protein coupled receptors that are proteolytically activated by a variety of proteases ^{2, 3}. Cleavage of PARs results in intracellular signaling mediated by activation of various G proteins including G_12/13, G_q, and G_i ^{2, 4-6}. The PAR family consists of 4 members, PAR1-PAR4, with PARs 1, 3, and 4 being primarily activated by thrombin, while PAR2 is activated by trypsin and …

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …

Relationship Of Adipokines With Insulin Sensitivity In African Americans., Maria P Martinez Cantarin, Scott W Keith, Stephanie Deloach, Yonghong Huan, Bonita Falkner

Department of Medicine Faculty Papers

INTRODUCTION: Cytokines produced by adipose tissue, including adiponectin, have been associated with metabolic abnormalities. The purpose of this study was to examine the relationship of insulin sensitivity measured by euglycemic hyperinsulinemic insulin clamp with plasma adiponectin and other adipokines in young adult African Americans.

METHODS: Participants were healthy African Americans. Anthropometric measures, blood pressure, an oral glucose tolerance test and an euglycemic hyperinsulinemic insulin clamp were performed. Insulin sensitivity measurements were adjusted for percentage of fat mass. Plasma concentrations of adiponectin, plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6) were assayed on plasma from fasting blood samples. Pearson correlation coefficients and …

Chronic Diseases: The Emerging Pandemic., Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

According to the 2011 World Health Organization Global Status Report, of the 57 million annual global deaths – a staggering 36 million or over 63% are due to chronic diseases.¹ Four noncommunicable diseases - namely cardiovascular, cancer, diabetes, and chronic respiratory diseases - emerge as the leading cause of mortality in the world, accounting respectively for 17, 7.6, 4.2, and 1.3 million deaths based on the latest available global epidemiology data. By 2020, global deaths due to chronic diseases are projected to worsen by at least 15 to 20%. It is estimated that the four major noncommunicable diseases will …

Health Needs Of Hiv-Infected Women In The United States: Insights From The Women Living Positive Survey., Kathleen E Squires, Sally L Hodder, Judith Feinberg, Dawn Averitt Bridge, Staats Abrams, Stephen P Storfer, Judith A Aberg

Department of Medicine Faculty Papers

The objective of this study was to describe attitudes, opinions, and perceived health needs of HIV-infected women in the United States. In this cross-sectional study, women were invited to participate in the Women Living Positive survey, a structured interview instrument with 45 questions. Collected data were deidentified and the margin of error was calculated as four percentage points. Incoming toll-free phone interviews were conducted from December 21, 2006, through March 14, 2007 among subjects recruited from a U.S. national network of AIDS counseling centers. Seven hundred HIV-infected women (43% African American, 28.5% Hispanic, 28.5% Caucasian; median age, 42.5 years) receiving …

Hydrophobicity As A Driver Of Mhc Class I Antigen Processing., Lan Huang, Matthew C Kuhls, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

The forces that drive conversion of nascent protein to major histocompatibility complex (MHC) class I-restricted peptides remain unknown. We explored the fundamental property of overt hydrophobicity as such a driver. Relocation of a membrane glycoprotein to the cytosol via signal sequence ablation resulted in rapid processing of nascent protein not because of the misfolded luminal domain but because of the unembedded transmembrane (TM) domain, which serves as a dose-dependent degradation motif. Dislocation of the TM domain during the natural process of endoplasmic reticulum-associated degradation (ERAD) similarly accelerated peptide production, but in the context of markedly prolonged processing that included nonnascent …

Kidney Injury Molecule-1 (Kim-1) As An Early Detection Tool For Acute Kidney Injury And Other Renal Diseases, John Fontanilla, Md, Won K. Han, M.D

Department of Medicine Faculty Papers

Introduction: Although serum creatinine is the standard metric tool for the detection of renal injury, its lack of sensitivity has made the early diagnosis of acute kidney injury (AKI) very difficult. In fact, the absence of sensitive AKI biomarkers has impaired progress in the nephrology field and had a detrimental effect on the design and outcome of AKI clinical trials. Recently, several proteins have shown potential in the early detection of acute and chronic kidney injuries.

Areas covered: This review discusses the current status of kidney injury molecule-1 (KIM-1) as a potential diagnostic tool in patients with various acute …

The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). Aspirin and clopidogrel are two frequently used anti-clotting agents with different mechanisms of action. Since LRPT may potentially be co-administered with either one of these agents, these studies were conducted to assess the effects of steady-state LRPT on the antiplatelet activity of steady-state clopidogrel or aspirin. Bleeding time …

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …

The Yin And Yang Of Fcγ Receptors In Itp, Steven E. Mckenzie

Department of Medicine Faculty Papers

The Fcγ receptors contribute to the susceptibility to autoimmune diseases such as ITP in several ways: (1) they modulate dendritic cell antigen processing and presentation, (2) they modulate antibody production by B cells, and (3) they participate in effector cell functions, such as phagocytosis, antibody-dependent cellular cytotoxicity, and mediator release. The key finding in recent years has been the appreciation that the activating Fcγ receptors, encoded by FCGR2A, -2C, -3A, and -3B, compete with the inhibitory Fcγ receptor, encoded by FCGR2B, to determine cellular responses to immune complexes and antibody-coated cells.

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon

Department of Cancer Biology Faculty Papers

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …

Multiple Forms Of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15., Nicholas J Wang, Alexander S Parokonny, Karen N Thatcher, Jennette Driscoll, Barbara M Malone, Naghmeh Dorrani, Marian Sigman, Janine M Lasalle, N Carolyn Schanen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the …