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Success Stories


Publications
Identification of a Small Molecule That Modifies MglA/SspA Interaction and Impairs Intramacrophage Survival of Francisella tularensis

PLoS ONE

Wrench AP, Gardner CL, Gonzalez CF, Lorca GL
PLoS ONE - vol. 8 1-14 (2013)

The transcription factors MglA and SspA of Francisella tularensis form a heterodimer complex and interact with the RNA polymerase to regulate the expression of the Francisella pathogenicity island (FPI) genes. These genes are essential for this pathogen’s virulence and survival within host cells. In this study, we used a small molecule screening to identify quinacrine […]

Publications
RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs

PLoS ONE

Robinson TJW, Liu JC, Vizeacoumar F, Sun T, Maclean N, Egan SE, Schimmer AD, Datti A, Zacksenhaus E
PLoS ONE - vol. 8 (2013)

Triple negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which only chemotherapy and radiation therapy are currently available. The retinoblastoma (RB1) tumor suppressor is frequently lost in human TNBC. Knockdown of RB1 in luminal BC cells was shown to affect response to endocrine, radiation and several antineoplastic drugs. However, the effect of RB1 […]

Publications
Fluorescence-Based High-Throughput Screening of Dicer Cleavage Activity

Journal of Biomolecular Screening

Podolska K, Sedlak D, Bartunek P, Svoboda P
Journal of Biomolecular Screening 1087057113497400 (2013)

Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer […]

Publications
A cell-based screening system for influenza A viral RNA transcription/replication inhibitors.

Scientific reports

Ozawa M, Shimojima M, Goto H, Watanabe S, Hatta Y, Kiso M, Furuta Y, Horimoto T, Peters NR, Hoffmann FM, Kawaoka Y
Scientific reports - vol. 3 1106 (2013)

Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/replication is a promising target for antiviral development, since it is essential for virus replication. Accordingly, an […]

Publications
Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity

Biological Psychiatry

McCormick AV, Wheeler JM, Guthrie CR, Liachko NF, Kraemer BC
Biological Psychiatry - vol. 73 464-471 (2013)

Background: Tauopathies, including Alzheimer’s disease and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease-modifying treatments exist for tauopathies. Methods: To identify drugs targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of tauopathy to screen a drug library containing […]

Publications
In vitro assessment of Macleaya cordata crude extract bioactivity and anticancer properties in normal and cancerous human lung cells

Experimental and Toxicologic Pathology

Liu M, Lin YL, Chen XR, Liao CC, Poo WK
Experimental and Toxicologic Pathology - vol. 65 775-787 (2013)

The purpose of this study is to assess the bioactivity and anticancer properties of Macleaya cordata crude extract in vitro using normal fetal lung fibroblast MRC5 and adenocarcinomic epithelial cell A549 as model systems,. Treatment of extract induced cell detachment, rounding, and irregularity in shape, in both normal and adenocarcinomic human lung cells, in accompanied […]

Publications
Identification of small molecules that promote human embryonic stem cell self-renewal

Biochemical and Biophysical Research Communications

Kumagai H, Suemori H, Uesugi M, Nakatsuji N, Kawase E
Biochemical and Biophysical Research Communications - vol. 434 710-716 (2013)

Human embryonic stem cells (hESCs) and induced pluripotent cells have the potential to provide an unlimited source of tissues for regenerative medicine. For this purpose, development of defined/xeno-free culture systems under feeder-free conditions is essential for the expansion of hESCs. Most defined/xeno-free media for the culture of hESCs contain basic fibroblast growth factor (bFGF). Therefore, […]

Publications
An in vivo zebrafish screen identifies organophosphate antidotes with diverse mechanisms of action.

Journal of biomolecular screening

Jin S, Sarkar KS, Jin YN, Liu Y, Kokel D, Van Ham TJ, Roberts LD, Gerszten RE, Macrae CA, Peterson RT
Journal of biomolecular screening - vol. 18 108-115 (2013)

Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a […]

Publications
Zebrafish based small molecule screens for novel DMD drugs

Drug Discovery Today: Technologies

Kawahara G, Kunkel LM
Drug Discovery Today: Technologies - vol. 10 e91-e96 (2013)

Recently, a number of chemical and drug screens using zebrafish embryos have been published. Using zebrafish dystrophin mutants, we screened a chemical library for small molecules that modulate the muscle phenotype and identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish. One chemical, aminophylline, which is known to be a non-selective phosphodiesterase (PDE) […]

Publications
Hit identification of novel heparanase inhibitors by structure- and ligand-based approaches

Bioorganic and Medicinal Chemistry

Gozalbes R, Mosulén S, Ortí L, Rodríguez-Díaz J, Carbajo RJ, Melnyk P, Pineda-Lucena A
Bioorganic and Medicinal Chemistry - vol. 21 1944-1951 (2013)

Heparanase is a key enzyme involved in the dissemination of metastatic cancer cells. In this study a combination of in silico techniques and experimental methods was used to identify new potential inhibitors against this target. A 3D model of heparanase was built from sequence homology and applied to the virtual screening of a library composed […]