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2014 15 Articles Back to Top
April 14th

Human embryonic stem cell derived islet progenitors mature inside an encapsulation device without evidence of increased biomass or cell escape

Pamela Itkin-Ansari Lab

Stem Cell Research

HIGHLIGHTS
• Encapsulated human embryonic stem cell (hESC) derived islet progenitors mature into functional islets in vivo
• Islet maturation does not require an increase in cell mass
• Encapsulated hES derived islets ameliorate diabetes in mice
• hESC do not escape from encapsulation devices and are therefore retrievable

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April 7th

Kinome-Wide Functional Analysis Highlights the Role of Cytoskeletal Remodeling in Somatic Cell Reprogramming

Tariq Rana Lab

Cell Stem Cell

HIGHLIGHTS
• Kinome-wide functional analysis identifies kinases that regulate reprogramming
• Four networks of 59 kinases show highly interconnected molecular functions
• TESK1 and LIMK2 modulate actin cytoskeleton through phosphorylation of COFILIN
• Crosstalk between ILK and TGFβ pathway enzymes regulates cytoskeletal remodeling

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March 31st

HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles

Lorenzo Puri Lab

Genes and Development

HIGHLIGHTS
• FAPs are cellular determinants of Duchenne Muscular Dystrophy pathogenesis
• FAPs from dystrophic muscles show lineage bi-potency & distinct patterns of chromatin accessibility and gene expression
• HDAC-regulated expression of microRNA controls composition of SWI/SNF complex
• HDAC inhibitors promote pro-myogenic activity of FAPs by promoting expression of myogenic microRNA and BAF60C

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March 24th

Positive Regulation of TRAF6-Dependent Innate Immune Responses by Protein Phosphatase PP1-γ

Sumit Chanda Lab

PLoS One

HIGHLIGHTS
• Protein Phosphatase PP1-γ was identified through a sub-genome gain of function screen as an activator of NFkB
• PP1-γ specifically regulates MyD88-dependent innate response pathways
• PP1-γ promotes TRAF6 E3 ligase activity
• The phosphatase is required for proper innate responses to ligand, viral and bacterial challenge in myeloid cell lines, primary cells, and mouse knockout macrophages

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March 20th

ROS regulate cardiac function in Drosophila via a novel paracrine mechanism

Rolf Bodmer Lab

Cell Reports

HIGHLIGHTS
• ROS control heart function via nearby non-myocytic pericardial cells
• Both elevating or diminishing ROS by antioxidants in pericardial cells alters heart function
• Paracrine ROS signaling in pericardial cells does not involve diffusion to cardiomyocytes
• ROS elicit MKK3-p38 signaling in pericardial cells to control cardiac function non-autonomously

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March 12nd

Inhibition of miR-25 Improves Cardiac Contractility in the Failing Heart

Mark Mercola Lab

Nature

HIGHLIGHTS
• Whole genome, functional screen identified microRNAs that suppress a key protein (SERCA2a) that regulates calcium and heart muscle contractility
• One microRNA, miR-25, potently affected heart muscle contractility in vitro and in vivo, and is pathologically upregulated in heart failure
• An antisense oligonucleotide, anti-miR-25, delivered intravenously normalized miR-25 and SERCA2a levels
• Anti-miR-25 halted established heart failure in mice and even restored cardiac function

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February 24th

PP2A-B55β Antagonizes Cyclin E1 Proteolysis and Promotes Its Dysregulation in Cancer

Charles Spruck Lab

Cancer Research

HIGHLIGHTS
• Cyclin E1 is a critical oncoprotein in many cancers, including triple-negative breast cancers (TNBCs) which lack targeted therapies
• Protein phosphatase PP2A-B55β was found to target cyclin E1 for dephosphorylation, leading to orderly initiation of DNA synthesis in normal cells
• Deregulated PP2A-B55β in cancers promotes cyclin E1 overexpression by protecting it from degradation by the SCFFbxw7 ubiquitin ligase
• PP2A-B55β inhibition in TNBC cells enforces cyclin E1 degradation and prevents tumor formation and metastasis progression in nude mice

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February 19th

Islet Antigen-Specific Th17 Cells Can Induce TNF-a-Dependent Autoimmune Diabetes

Linda Bradley Lab

The Journal of Immunology

HIGHLIGHTS
• Type I diabetes (T1D), which results from autoimmune destruction of insulin-producing β-cells, is known to be orchestrated by Th1 CD4 cells.
• Unlike the established contribution of Th1 CD4 cells, the contribution of Th17 CD4 cells to T1D, which secrete IL-17, is controversial.
• We show that Th17 cells can be reprogrammed to Th1 cells in response to pancreatic inflammation.
• Prevention of Th1 cell development by deficiencies of Stat4, IFN-γR, and IFN-γ resulted in diabetes elicited by Th17 cells.
• This study identifies a new mechanism by which Th17 cells contribute to diabetes.

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February 10th

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Tariq Rana Lab

Molecular Cell

HIGHLIGHTS
• Genome-wide RNAi screen identified 20 lincRNAs controlling pluripotency
• lincRNA TUNA is required for pluripotency and neural differentiation
• TUNA interacts with RNA-binding proteins through a conserved sequence
• TUNA expression in Huntington’s patients was associated with disease grade

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February 7th

Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice

Hudson Freeze Lab

The FASEB Journal

HIGHLIGHTS
• MPI-CDG, a potentially lethal human Glycosylation Disorder disease is treated with mannose, a simple sugar supplement
• We created a viable hypomorphic mouse model, hoping to mimic MPI-CDG
• Providing mannose during embryogenesis was found to be either lethal or resulted in severe eye defects (50%)
• Providing mannose during embryogenesis was found to be either lethal or resulted in severe eye defects (50%)

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January 27th

Small-molecule IAP antagonists sensitive cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs

Kristiina Vuori Lab & Nick Cosford Lab

Molecular Cancer Therapeutics

HIGHLIGHTS
• Inhibiting the inhibitors: A new class of inhibitor of apoptosis (IAP) antagonists is presented
• Non-toxic as single agents and do not induce TNF production
• Sensitize resistant cancer cells, but not normal, cells, to cell death induced by TNF-related apoptosis inducing ligand (TRAIL)
• TRAIL + our IAP antagonists thus represent a novel co-chemotherapy whereby each agent is inactive alone but together result in cancer cell death

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January 20th

N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells

Crystal Zhao Lab

Nature Cell Biology

HIGHLIGHTS
• m6A MTAses are enzymes that methylate the amino group at the C-6 position of adenines in DNA
• Mettl3 and Mettl4 are m6A MTAses that work synergistically to control m6A formation in mammalian cells
• Knockdown of Mettl13 and Mettl14 disables mouse embryonic stem cell self-renewal capacity
• M6A methylation is an essential RNA regulatory mechanism in mammalian cells

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January 13rd

Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal

Malene Hansen and Rolf Bodmer Labs

Aging Cell

HIGHLIGHTS
• Reduced levels of ILK extends lifespan and thermotolerance in C. elegans via the transcription factor HSF-1
• HSF-1 induces these systemic effects in C. elegans with reduced ILK levels via a complex neuronal circuit

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January 13rd

A dual role for integrin-linked kinase and β1-integrin

Rolf Bodmer and Malene Hansen Labs

Aging Cell

HIGHLIGHTS
• ILK and beta-integrin are necessary for establishing and maintaining normal heart structure in Drosophila
• Fine tuning the pathway can retard the age-dependent decline in Drosophila heart performance and extend lifespan

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January 6th

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

Barbara Ranscht Lab

PNAS

HIGHLIGHTS
• Mutiple sclerosis destroys the myelin in the central nervous system (CNS)
• Contactin-1 was known to mediate myelin attachment to axons in the peripheral nervous system
• Study shows that Contactin-1 is important for producing myelin AND attaching it to axons in the CNS
• Relevant because to regenerate myelin for patients with MS—Contactin-1 is required

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2013 6 Articles Back to Top
December 30th

The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL

Tariq Rana Lab

PNAS

HIGHLIGHTS
• Large intergenic noncoding RNAs (lincRNAs) are known to regulate cell functions
• A new molecule called “THRIL”, is comprised of a lincRNA bound to a nuclear ribonucleoprotein
• “THRIL” regulates the TNF-alpha gene by binding to its promoter
• THRIL expression correlates with the severity of Kawasaki disease and may contribute to other inflammatory diseases

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December 23rd

A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity

Robert Wechsler-Reya Lab

Nature Neuroscience

HIGHLIGHTS
• Nestin expressing progenitor (NEP) cells are discovered in the external granule layer of the brain
• DNA repair mechanisms are less active than other granule neuron precursors (GNPs)
• NEP cells are more likely to give rise to tumors compared to GNPs
• Studying the cells may help find new approaches to targeting brain cells

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December 16th

A role for Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 (PGC-1) in the Regulation of Cardiac Mitochondrial Phospholipid Biosynthesis

Daniel Kelly Lab

JBC The Journal of Biological Chemistry

CAPSULE
Background: Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) α and β are transcriptional regulators of mitochondrial metabolism.
Results: Loss of PGC-1 coactivators in mouse heart causes a defect in phospholipid biosynthesis resulting in mitochondrial ultrastructural abnormalities.
Conclusion: PGC-1 coactivators coordinately regulate mitochondrial metabolism and structure.
Significance: The mitochondrial phenotype of PGC-1-deficient mice resembles that of humans with genetic defects in mitochondrial phospholipid biosynthesis (Barth Syndrome).

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December 9th

The Inhibitory Receptor BTLA Controls γδ T Cell Homeostasis and Inflammatory Responses

Carl Ware Lab

Immunity

HIGHLIGHTS
• IL-7 induces BTLA expression and RORγt represses BTLA transcription
• BTLA restricts γδ T cell expansion during homeostasis and inflammation
• BTLA regulates γδ T cell production of IL-17 and TNF
• BTLA-deficient animals are susceptible to γδ T cell-dependent dermatitis

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December 2nd

Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription

Stuart Lipton Lab

Cell

HIGHLIGHTS
• hiPSC-DA neurons (hNs) with PD mutation (SNCAA53T) manifest nitrosative stress
• SNCAA53T or mitochondrial toxins induce S-nitrosylated (SNO)-MEF2C in hNs
• S-nitrosylation of MEF2C reduces PGC1α expression and impairs mitochondrial function
• Reactivation of MEF2-PGC1α rescues SNCAA53T hNs from nitrosative stress-induced death

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November 26th

Context-Specific BAFF-R Signaling by the NF-κB and PI3K Pathways

Robert Rickert Lab

Cell Reports

HIGHLIGHTS
• IKK1 loss creates a bottleneck, but not an impasse, in transitional B cell maturation
• Acute BAFF-dependent survival of mature B cells is IKK1 independent
• Coinactivation of Cd19 and Ikk1 prevents the generation of mature B cells
• Activation of the PI3K pathway partially rescues B cell defects in Baff−/− mice

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