'It is uncertain how antiviral lymphocytes are activated in draining lymph nodes, the site where adaptive immune responses are initiated. Here, using intravital microscopy we show that after infection of mice with vaccinia virus (a large DNA virus) or vesicular stomatitis virus (a small RNA virus), virions drained to the ... More
Profiling antibody responses by multiparametric analysis of primary B cells.
AuthorsStory CM, Papa E, Hu CC, Ronan JL, Herlihy K, Ploegh HL, Love JC,
JournalProc Natl Acad Sci U S A
PubMed ID19004776
'Determining the efficacy of a vaccine generally relies on measuring neutralizing antibodies in sera. This measure cannot elucidate the mechanisms responsible for the development of immunological memory at the cellular level, however. Quantitative profiles that detail the cellular origin, extent, and diversity of the humoral (antibody-based) immune response would improve ... More
Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis.
AuthorsHirose Y, Saijou E, Sugano Y, Takeshita F, Nishimura S, Nonaka H, Chen YR, Sekine K, Kido T, Nakamura T, Kato S, Kanke T, Nakamura K, Nagai R, Ochiya T, Miyajima A,
JournalProc Natl Acad Sci U S A
PubMed ID22371575
'Hyaluronic acid (HA) has been implicated in the proliferation and metastasis of tumor cells. However, most previous studies were conducted on extracellular matrix or pericellular HA, and the role of circulating HA in vivo has not been studied. HA is rapidly cleared from the bloodstream. The scavenger receptor Stabilin-2 (Stab2) ... More
Reconstruction of 3D stacked-up structures by rat small hepatocytes on microporous membranes.
AuthorsSudo R, Mitaka T, Ikeda M, Tanishita K
JournalFASEB J
PubMed ID16107536
'The three-dimensional (3D) culture of hepatocytes is essential for the reconstruction of functional hepatic tissues in vitro. In the present experiment, we developed a 3D-culture method in order to reconstruct hepatic cordlike structures by stacking up two-dimensional (2D) tissues composed of rat small hepatocytes (SHs), which are hepatic progenitor cells. ... More
TGF-beta1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodeling axis: role for PAI-1.
AuthorsWilkins-Port CE, Ye Q, Mazurkiewicz JE, Higgins PJ,
JournalCancer Res
PubMed ID19383899
'The phenotypic switching called epithelial-to-mesenchymal transition is frequently associated with epithelial tumor cell progression from a comparatively benign to an aggressive, invasive malignancy. Coincident with the emergence of such cellular plasticity is an altered response to transforming growth factor-beta (TGF-beta) as well as epidermal growth factor (EGF) receptor amplification. TGF-beta ... More
Examination of laser microbeam cell lysis in a PDMS microfluidic channel using time-resolved imaging.
'We use time-resolved imaging to examine the lysis dynamics of non-adherent BAF-3 cells within a microfluidic channel produced by the delivery of single highly-focused 540 ps duration laser pulses at lambda = 532 nm. Time-resolved bright-field images reveal that the delivery of the pulsed laser microbeam results in the formation ... More
A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo.
AuthorsGibson VB, Benson RA, Bryson KJ, McInnes IB, Rush CM, Grassia G, Maffia P, Jenkinson EJ, White AJ, Anderson G, Brewer JM, Garside P,
JournalBlood
PubMed ID22271449
'In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow ... More
Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.
AuthorsRalston KS, Solga MD, Mackey-Lawrence NM, Somlata, Bhattacharya A, Petri WA,
Journal
PubMed ID24717428
'Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named '
Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone.
AuthorsBajénoff M, Glaichenhaus N, Germain RN,
JournalJ Immunol
PubMed ID18768849
'Although a great deal is known about T cell entry into lymph nodes, much less is understood about how T lymphocytes access the splenic white pulp (WP). We show in this study that, as recently described for lymph nodes, fibroblastic reticular cells (FRCs) form a network in the T cell ... More
Heterogeneous breast tumoroids: An in vitro assay for investigating cellular heterogeneity and drug delivery.
'Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can ... More
Initiation of facial motoneurone migration is dependent on rhombomeres 5 and 6.
AuthorsStuder M
JournalDevelopment
PubMed ID11585797
'In mammals, facial branchiomotor (FBM) neurones are born in ventral rhombomere (r) 4 and migrate through r5 to dorsal r6 where they form the facial motor nucleus. This pattern of migration gives rise to the distinctive appearance of the internal genu of the facial nerve, which is lacking in birds. ... More
Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages.
AuthorsAlvarez M, Casadevall A,
JournalBMC Immunol
PubMed ID17705844
'BACKGROUND: The interaction between macrophages and Cryptococcus neoformans (Cn) is critical for containing dissemination of this pathogenic yeast. However, Cn can either lyse macrophages or escape from within them through a process known as phagosomal extrusion. Both events result in live extracellular yeasts capable of reproducing and disseminating in the ... More
JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.
AuthorsVentura JJ, Cogswell P, Flavell RA, Baldwin AS, Davis RJ
JournalGenes Dev
PubMed ID15545623
The c-Jun NH(2)-terminal kinase (JNK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of JNK in tumor necrosis factor (TNF)-stimulated cell death using fibroblasts isolated from wild-type, Mkk4(-/-) Mkk7(-/-), and Jnk1(-/-) Jnk2(-/-) mice. We demonstrate that JNK can act to ... More
T cell antigen receptor signaling and immunological synapse stability require myosin IIA.
AuthorsIlani T, Vasiliver-Shamis G, Vardhana S, Bretscher A, Dustin ML,
JournalNat Immunol
PubMed ID19349987
Immunological synapses are initiated by signaling in discrete T cell antigen receptor microclusters and are important for the differentiation and effector functions of T cells. Synapse formation involves the orchestrated movement of microclusters toward the center of the contact area with the antigen-presenting cell. Microcluster movement is associated with centripetal ... More
Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells.
AuthorsKizil C, Brand M,
JournalPLoS One
PubMed ID22076157
The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. ... More
Exploitation of other social amoebae by Dictyostelium caveatum.
AuthorsNizak C, Fitzhenry RJ, Kessin RH,
JournalPLoS ONE
PubMed ID17299592
Dictyostelium amoebae faced with starvation trigger a developmental program during which many cells aggregate and form fruiting bodies that consist of a ball of spores held aloft by a thin stalk. This developmental strategy is open to several forms of exploitation, including the remarkable case of Dictyostelium caveatum, which, even ... More
Impaired dendritic cell function in aging leads to defective antitumor immunity.
AuthorsGrolleau-Julius A, Harning EK, Abernathy LM, Yung RL,
JournalCancer Res
PubMed ID18676859
We recently reported that bone marrow-derived dendritic cells (DC) from aged miced are less effective than their young counterparts in inducing the regression of B16-ovalbumin (OVA) melanomas. To examine the underlying mechanisms, we investigated the effect of aging on DC tumor antigen presentation and migration. Although aging does not affect ... More
S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons.
AuthorsNott A, Watson PM, Robinson JD, Crepaldi L, Riccio A,
JournalNature
PubMed ID18754010
Brain-derived neurotrophic factor (BDNF) and other neurotrophins have a vital role in the development of the rat and mouse nervous system by influencing the expression of many specific genes that promote differentiation, cell survival, synapse formation and, later, synaptic plasticity. Although nitric oxide (NO) is known to be an important ... More
ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages.
AuthorsJehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ, Vandivier RW, Wang N, Greenberg S, Dale BM, Qin C, Henson PM, Tall AR
JournalJ Cell Biol
PubMed ID16908670
The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the clearance of apoptotic cells. Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic ... More
Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1.
53BP1 is a key component of the genome surveillance network activated by DNA double strand breaks (DSBs). Despite its known accumulation at the DSB sites, the spatiotemporal aspects of 53BP1 interaction with DSBs and the role of other DSB regulators in this process remain unclear. Here, we used real-time microscopy ... More
Natural killer cell behavior in lymph nodes revealed by static and real-time imaging.
AuthorsBajénoff M, Breart B, Huang AY, Qi H, Cazareth J, Braud VM, Germain RN, Glaichenhaus N
JournalJ Exp Med
PubMed ID16505138
Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo during the early phases of an adaptive immune response, we have used immunohistochemical analysis and dynamic intravital imaging to study ... More
Rho GDP dissociation inhibitor protects cancer cells against drug-induced apoptosis.
AuthorsZhang B, Zhang Y, Dagher MC, Shacter E
JournalCancer Res
PubMed ID16024605
Rho GDP dissociation inhibitor (RhoGDI) plays an essential role in control of a variety of cellular functions through interactions with Rho family GTPases, including Rac1, Cdc42, and RhoA. RhoGDI is frequently overexpressed in human tumors and chemo-resistant cancer cell lines, raising the possibility that RhoGDI might play a role in ... More
Contagious apoptosis facilitated by the HIV-1 envelope: fusion-induced cell-to-cell transmission of a lethal signal.
AuthorsAndreau K, Perfettini JL, Castedo M, Métivier D, Scott V, Pierron G, Kroemer G
JournalJ Cell Sci
PubMed ID15494371
Cells expressing the human immunodeficiency virus (HIV-1) envelope glycoprotein complex (Env) can fuse with CD4+ cells. When the apoptotic pathway is initiated in Env+ cells ('donor cells'), co-culture with a healthy CD4+ fusion partner ('acceptor cells') results in apoptosis of the syncytium and thus is 'contagious'. The cell-to-cell transmission of ... More
NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.
AuthorsPerfettini JL, Roumier T, Castedo M, Larochette N, Boya P, Raynal B, Lazar V, Ciccosanti F, Nardacci R, Penninger J, Piacentini M, Kroemer G
JournalJ Exp Med
PubMed ID14993250
The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic ... More
Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment.
AuthorsAcuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM
JournalCancer Res
PubMed ID16397239
The role of specific stromal-derived matrix metalloproteinases (MMPs) was analyzed in experimental metastasis assays in wild-type and either MMP-9, MMP-7, or MMP-2 null mice. MMP-9 null mice showed an 81% reduction in Lewis lung carcinoma tumor number, whereas MMP-7 null mice showed a 42% increase in tumor number, and there ... More
Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium.
AuthorsHuang M, Matthews K, Siahaan TJ, Kevil CG
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID15319185
Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet beta-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of ... More
Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease.
Statins are potent, cholesterol-lowering agents with newly appreciated, broad anti-inflammatory properties, largely based upon their ability to block the prenylation of Rho GTPases, including RhoA. Because phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, which is inhibited by RhoA, we sought to determine whether statins enhanced efferocytosis. ... More
A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis.
AuthorsGe L, Ly Y, Hollenberg M, DeFea K
JournalJ Biol Chem
PubMed ID12821670
Cell motility during wound healing and inflammation is often dependent on the ability of the cell to sense a gradient of agonist. The first step in this process is the extension of a pseudopod in the direction of the agonist, and a diverse set of signals mediate pseudopod extension by ... More
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.
AuthorsBao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN
JournalNature
PubMed ID17051156
Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying tumour radioresistance have remained elusive. Here we show that cancer stem cells contribute to glioma radioresistance through ... More
Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin II-induced cardiomyocyte hypertrophy.
AuthorsHingtgen SD, Tian X, Yang J, Dunlay SM, Peek AS, Wu Y, Sharma RV, Engelhardt JF, Davisson RL
JournalPhysiol Genomics
PubMed ID16670255
Angiotensin II (ANG II) has profound effects on the development and progression of pathological cardiac hypertrophy; however, the intracellular signaling mechanisms are not fully understood. In this study, we used genetic tools to test the hypothesis that increased formation of superoxide (O2-*) radicals from a Rac1-regulated Nox2-containing NADPH oxidase is ... More
Sensing of HIV-1 by TLR8 activates human T cells and reverses latency.
AuthorsMeås HZ, Haug M, Beckwith MS, Louet C, Ryan L, Hu Z, Landskron J, Nordbø SA, Taskén K, Yin H, Damås JK, Flo TH
JournalNat Commun
PubMed ID31919342
'During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well ... More
Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.
Authors
JournalNat Mater
PubMed ID26726994
Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.
AuthorsAya-Bonilla CA, Morici M, Hong X, McEvoy AC, Sullivan RJ, Freeman J, Calapre L, Khattak MA, Meniawy T, Millward M, Ziman M, Gray ES
JournalBr J Cancer
PubMed ID32037400
'Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application.' ... More
Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma.
Authors
JournalGut
PubMed ID30121627
Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion.
Authors
JournalNat Commun
PubMed ID32210228
Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells.
Authors
JournalNat Commun
PubMed ID31092822
Galanin modulates the neural niche to favour perineural invasion in head and neck cancer.
Authors
JournalNat Commun
PubMed ID25917569
Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip.
Authors
JournalAdv Sci (Weinh)
PubMed ID32670763
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis.
Authors
JournalNat Commun
PubMed ID34188051
Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells.
Authors
JournalCell Stem Cell
PubMed ID30581079
Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation.
Authors
JournalNat Commun
PubMed ID32444791
Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.
Authors
JournalNat Commun
PubMed ID31296856
Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells.
AuthorsSarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, Tran CM, Chu CR, Horvath S, Qi LS, Bhutani N, Rando TA, Sebastiano V
JournalNat Commun
PubMed ID32210226
Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can ... More
Co-culture of induced pluripotent stem cells with cardiomyocytes is sufficient to promote their differentiation into cardiomyocytes.
AuthorsChu AJ, Zhao EJ, Chiao M, Lim CJ
JournalPLoS One
PubMed ID32243463
Various types of stem cells and non-stem cells have been shown to differentiate or transdifferentiate into cardiomyocytes by way of co-culture with appropriate inducer cells. However, there is a limited demonstration of a co-culture induction system utilizing stem cell-derived cardiomyocytes as a stimulatory source for cardiac reprogramming (of stem cells ... More
A Platform for Studying of the Three-Dimensional Migration of Hematopoietic Stem/Progenitor Cells.
AuthorsLee E, Kim J, Kang Y, Shin JW
JournalTissue Eng Regen Med
PubMed ID32002840
Hematopoietic stem/progenitor cells (HSPCs) have the property to return to the bone marrow, which is believed to be critical in situations such as HSPC transplantation. This property plays an important role in the stemness, viability, and proliferation of HSPCs, also. However, most in vitro models so far have not sufficiently ... More
C3a elicits unique migratory responses in immature low-density neutrophils.
AuthorsHsu BE, Roy J, Mouhanna J, Rayes RF, Ramsay L, Tabariès S, Annis MG, Watson IR, Spicer JD, Costantino S, Siegel PM
JournalOncogene
PubMed ID32020055
Neutrophils represent the immune system's first line of defense and are rapidly recruited into inflamed tissue. In cancer associated inflammation, phenotypic heterogeneity has been ascribed to this cell type, whereby neutrophils can manifest anti- or pro-metastatic functions depending on the cellular/micro-environmental context. Here, we demonstrate that pro-metastatic immature low-density neutrophils ... More
Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.
AuthorsVoloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, Palti Y
JournalCancer Immunol Immunother
PubMed ID32144446
Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, ... More
Inhibition of miR30a-3p by sulforaphane enhances gap junction intercellular communication in pancreatic cancer.
AuthorsGeorgikou C, Yin L, Gladkich J, Xiao X, Sticht C, Torre C, Gretz N, Gross W, Schäfer M, Karakhanova S, Herr I
JournalCancer Lett
PubMed ID31678166
The therapy resistance of pancreatic cancer is associated with the loss of gap junction intercellular communication and connexin 43 expression. The broccoli isothiocyanate sulforaphane restored these features and therapy sensitivity. We investigated whether microRNA signaling is involved. Established cell lines and a patient tissue array (n?=?96) were evaluated by miRNA ... More