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314 results on '"Kolesnick, R."'

2. C16-Ceramide Elevations in COVID-19-Associated ARDS

Author

Petrache, I., primary, Pujadas, E., additional, Ganju, A., additional, Serban, K.A., additional, Bronova, I., additional, Babbs, B., additional, Egersdorf, N., additional, Hume, P., additional, Goel, K., additional, Janssen, W.J., additional, Berdyshev, E., additional, Cordon-Cardo, C., additional, and Kolesnick, R., additional

Published
2022
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3. Acid sphingomyelinase deactivation post-ischemia/ reperfusion promotes cerebral angiogenesis and brain remodeling via small extracellular vesicles

Author

Mohamud Yusuf, A, primary, Hagemann, N, additional, Zhang, X, additional, Zafar, M, additional, Hussner, T, additional, Bromkamp, C, additional, Martiny, C, additional, Tertel, T, additional, Börger, V, additional, Schumacher, F, additional, Solari, FA, additional, Hasenberg, M, additional, Kleinschnitz, C, additional, Doeppner, TR, additional, Kleuser, B, additional, Sickmann, A, additional, Gunzer, M, additional, Giebel, B, additional, Kolesnick, R, additional, Gulbins, E, additional, and Hermann, DM, additional

Published
2021
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5. Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts

Author

Grassme, H., Jendrossek, V., Riehle, A., von Kurthy, G., Berger, J., Schwarz, H., Weller, M., Kolesnick, R., and Gulbins, E.

Abstract

Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen., Author(s): H. Grassme [1]; V. Jendrossek [2]; A. Riehle [1]; G. von Kurthy [3]; J. Berger [4]; H. Schwarz [4]; M. Weller [3]; R. Kolesnick [5]; E. Gulbins (corresponding author) [...]

Published
2003
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6. T cell-derived interferon-gamma programs stem cell death in immune-mediated intestinal damage

Author

Cluster B, Dagcentrum, Opleiding Neurologie, Child Health, Regenerative Medicine and Stem Cells, MDL onderzoek 2, Onderzoek, SCT patientenzorg, Infection & Immunity, Takashima, S., Martin, M. L., Jansen, S. A., Fu, Y., Bos, J., Chandra, D., O'Connor, M. H., Mertelsmann, A. M., Vinci, P., Kuttiyara, J., Devlin, S. M., Middendorp, S., Calafiore, M., Egorova, A., Kleppe, M., Lo, Y., Shroyer, N. F., Cheng, E. H., Levine, R. L., Liu, C., Kolesnick, R., Lindemans, C. A., Hanash, A. M., Cluster B, Dagcentrum, Opleiding Neurologie, Child Health, Regenerative Medicine and Stem Cells, MDL onderzoek 2, Onderzoek, SCT patientenzorg, Infection & Immunity, Takashima, S., Martin, M. L., Jansen, S. A., Fu, Y., Bos, J., Chandra, D., O'Connor, M. H., Mertelsmann, A. M., Vinci, P., Kuttiyara, J., Devlin, S. M., Middendorp, S., Calafiore, M., Egorova, A., Kleppe, M., Lo, Y., Shroyer, N. F., Cheng, E. H., Levine, R. L., Liu, C., Kolesnick, R., Lindemans, C. A., and Hanash, A. M.

Published
2019

7. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage

Author

Takashima, S., primary, Martin, M. L., additional, Jansen, S. A., additional, Fu, Y., additional, Bos, J., additional, Chandra, D., additional, O’Connor, M. H., additional, Mertelsmann, A. M., additional, Vinci, P., additional, Kuttiyara, J., additional, Devlin, S. M., additional, Middendorp, S., additional, Calafiore, M., additional, Egorova, A., additional, Kleppe, M., additional, Lo, Y., additional, Shroyer, N. F., additional, Cheng, E. H., additional, Levine, R. L., additional, Liu, C., additional, Kolesnick, R., additional, Lindemans, C. A., additional, and Hanash, A. M., additional

Published
2019
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10. Phase II Prospective Trial to Assess the Feasibility and Efficacy of Dynamic 24Gy Single Dose Ablative Stereotactic Radiation Therapy in Oligometastatic Human Cancer

Author

Greco, C., primary, Pares, O., additional, Pimentel, N., additional, Possanzini, M., additional, Louro, V., additional, Morales, J., additional, Nunes, B., additional, Castanhera, J., additional, Oliveira, C., additional, Silva, A., additional, Vaz, S., additional, Costa, D., additional, Kolesnick, R., additional, and Fuks, Z., additional

Published
2018
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14. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration

Author

Lindemans, C.A., Calafiore, M. (Marco), Mertelsmann, A.M. (Anna M.), O'Connor, M.H. (Margaret H.), Dudakov, J.A. (Jarrod A.), Jenq, R.R. (Robert R.), Velardi, E. (Enrico), Young, L.F. (Lauren F.), Smith, O.M. (Odette M.), Lawrence, G. (Gillian), Ivanov, J.A. (Juliet A.), Fu, Y.-Y. (Ya-Yuan), Takashima, S. (Shuichiro), Hua, G. (Guoqiang), Martin, M.L. (Maria L.), O'Rourke, K.P. (Kevin P.), Lo, Y.-H. (Yuan-Hung), Mokry, M. (Michal), Romera Hernández, M. (Mónica), Cupedo, T. (Tom), Dow, L.E. (Lukas E.), Nieuwenhuis, E.E.S. (Edward), Shroyer, N.F. (Noah F.), Liu, C. (Chen), Kolesnick, R. (Richard), Van Den Brink, M.R.M. (Marcel R. M.), Hanash, A.M. (Alan M.), Lindemans, C.A., Calafiore, M. (Marco), Mertelsmann, A.M. (Anna M.), O'Connor, M.H. (Margaret H.), Dudakov, J.A. (Jarrod A.), Jenq, R.R. (Robert R.), Velardi, E. (Enrico), Young, L.F. (Lauren F.), Smith, O.M. (Odette M.), Lawrence, G. (Gillian), Ivanov, J.A. (Juliet A.), Fu, Y.-Y. (Ya-Yuan), Takashima, S. (Shuichiro), Hua, G. (Guoqiang), Martin, M.L. (Maria L.), O'Rourke, K.P. (Kevin P.), Lo, Y.-H. (Yuan-Hung), Mokry, M. (Michal), Romera Hernández, M. (Mónica), Cupedo, T. (Tom), Dow, L.E. (Lukas E.), Nieuwenhuis, E.E.S. (Edward), Shroyer, N.F. (Noah F.), Liu, C. (Chen), Kolesnick, R. (Richard), Van Den Brink, M.R.M. (Marcel R. M.), and Hanash, A.M. (Alan M.)

Abstract

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5 + crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regul

Published
2015
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19. Crypt base columnar stem cells in small intestines of mice are radioresistant

Author

Hua, G., Thin, T.H., Feldman, R., Haimovitz-Friedman, A., Clevers, H., Fuks, Z., Kolesnick, R., Hua, G., Thin, T.H., Feldman, R., Haimovitz-Friedman, A., Clevers, H., Fuks, Z., and Kolesnick, R.

Abstract

BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that they are highly radiosensitive. Cycling crypt base columnar cells (CBCs) at crypt positions +1-3 recently were defined as an alternative population of ISCs. Little is known about the sensitivity of this stem cell population to radiation. METHODS: Radiation-induced lethality of CBCs was quantified kinetically in Lgr5-lacZ transgenic mice. gamma-H2AX, BRCA1, RAD51, and DNA-PKcs foci were used as DNA repair surrogates to investigate the inherent ability of CBCs to recognize and repair double-strand breaks. 5-ethynyl-2'-deoxyuridine and 5-bromo-2'-deoxyuridine incorporation assays were used to study patterns of CBC growth arrest and re-initiation of cell cycling. Apoptosis was evaluated by caspase-3 staining. RESULTS: CBCs are relatively radioresistant, repairing DNA by homologous recombination significantly more efficiently than transit amplifying progenitors or villus cells. CBCs undergo apoptosis less than 24 hours after irradiation (32% +/- 2% of total lethality) or mitotic death at 24-48 hours. Survival of CBCs at 2 days predicts crypt regeneration at 3.5 days and lethality from gastrointestinal syndrome. Crypt repopulation originates from CBCs that survive irradiation. CONCLUSIONS: Adult ISCs in mice can cycle rapidly yet still be radioresistant. Importantly, homologous recombination can protect adult stem cell populations from genotoxic stress. These findings broaden and refine concepts of the phenotype of adult stem cells., BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that they are highly radiosensitive. Cycling crypt base columnar cells (CBCs) at crypt positions +1-3 recently were defined as an alternative population of ISCs. Little is known about the sensitivity of this stem cell population to radiation. METHODS: Radiation-induced lethality of CBCs was quantified kinetically in Lgr5-lacZ transgenic mice. gamma-H2AX, BRCA1, RAD51, and DNA-PKcs foci were used as DNA repair surrogates to investigate the inherent ability of CBCs to recognize and repair double-strand breaks. 5-ethynyl-2'-deoxyuridine and 5-bromo-2'-deoxyuridine incorporation assays were used to study patterns of CBC growth arrest and re-initiation of cell cycling. Apoptosis was evaluated by caspase-3 staining. RESULTS: CBCs are relatively radioresistant, repairing DNA by homologous recombination significantly more efficiently than transit amplifying progenitors or villus cells. CBCs undergo apoptosis less than 24 hours after irradiation (32% +/- 2% of total lethality) or mitotic death at 24-48 hours. Survival of CBCs at 2 days predicts crypt regeneration at 3.5 days and lethality from gastrointestinal syndrome. Crypt repopulation originates from CBCs that survive irradiation. CONCLUSIONS: Adult ISCs in mice can cycle rapidly yet still be radioresistant. Importantly, homologous recombination can protect adult stem cell populations from genotoxic stress. These findings broaden and refine concepts of the phenotype of adult stem cells.

Published
2012

21. RADIOBIOLOGY

Author

Artesi, M., primary, Kroonen, J., additional, Deprez, M., additional, Bredel, M., additional, Chakravarti, A., additional, Poulet, C., additional, Seute, T., additional, Rogister, B., additional, Bours, V., additional, Robe, P., additional, Liu, S.-C., additional, Chernikova, S., additional, Merchant, M., additional, Jang, T., additional, Zollner, S., additional, Kruschinski, A., additional, Ahn, G.-o., additional, Recht, L., additional, Brown, M., additional, Moyal, E. C.-J., additional, Delmas, C., additional, Taurand, M., additional, Mazoyer, S., additional, Farge, M., additional, Toulas, C., additional, Rao, S., additional, Thompson, C., additional, Cheng, J., additional, Haimovitz-Friedman, A., additional, Fuks, Z., additional, Kolesnick, R., additional, Wen, Q., additional, Jalilian, L., additional, Essock-Burns, E., additional, Li, Y., additional, Cha, S., additional, Chang, S., additional, Prados, M., additional, Butowski, N., additional, Nelson, S., additional, Ke, C., additional, Tran, K., additional, Di Donato, A. T., additional, Ru, N., additional, Linskey, M. E., additional, Limoli, C., additional, and Zhou, Y.-H., additional

Published
2013
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22. Host-Derived IL-22 Protects Intestinal Stem Cells from GVHD

Author

Hanash, A., primary, Dudakov, J., additional, Hua, G., additional, O'Connor, M., additional, Jenq, R., additional, Holland, A., additional, Smith, O., additional, Liu, C., additional, Fouser, L., additional, Kolesnick, R., additional, Blazar, B., additional, and van den Brink, M., additional

Published
2012
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23. jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans.

Author

Villanueva, A, Lozano, J, Morales, A, Lin, X, Deng, X, Hengartner, M O, Kolesnick, R N, Villanueva, A, Lozano, J, Morales, A, Lin, X, Deng, X, Hengartner, M O, and Kolesnick, R N

Abstract

Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele, jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.

Published
2001

30. Sphingosine 1-phosphate preserves fertility in irradiated female mice without propagating genomic damage in offspring

Author

Paris, F., Perez, G.I., Fuks, Z., Haimovitz-Friedman, A., Nguyen, H., Bose, M., Ilagan, A., Hunt, P.A., Morgan, W.F., Tilly, J.L., and Kolesnick, R.

Abstract

Author(s): F. Paris; G.I. Perez; Z. Fuks; A. Haimovitz-Friedman; H. Nguyen; M. Bose; A. Ilagan; P.A. Hunt; W.F. Morgan; J.L. Tilly; R. Kolesnick Nature Med. 8, 901-902 (2002). Page 902, [...]

Published
2002
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47. Sphingosine 1-phosphate s a therapeutic agent.

Author

Spiegel, S. and Kolesnick, R.

Subjects
SPHINGOSINE, METABOLITES
Abstract

The bioactive sphingolipid metabolite sphingosine-1-phosphate (SIP), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions — both inside and outside of cells. SIP is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by SIP or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of SIP and ceramide, another important sphingolipid metabotite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in SIP and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with SIP. Understanding the biosynthesis, metabolism and functions of SIP can uncover new targets for the pharmaceutical and therapeutic applications of S1P. [ABSTRACT FROM AUTHOR]

Published
2002
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48. CD95-mediated apoptosis in vivo involves acid sphingomyelinase.

Author

Kirschnek, S, Paris, F, Weller, M, Grassme, H, Ferlinz, K, Riehle, A, Fuks, Z, Kolesnick, R, and Gulbins, E

Abstract

Acid sphingomyelinase (ASM) is reported to have an essential function in stress-induced apoptosis although the physiological function of ASM in receptor-triggered apoptosis is unknown. Here, we delineate a pivotal role for ASM in CD95-triggered apoptosis of peripheral lymphocytes or hepatocytes in vivo. We employed intravenous injection of anti-CD4 antibodies or phytohemagglutinin that was previously shown to result in apoptosis of peripheral blood lymphocytes or hepatocytes via the endogenous CD95/CD95 ligand system. Our results demonstrate a high susceptibility in normal mice whereas ASM knock-out mice fail to immunodeplete T cells or develop autoimmune-like hepatitis. Likewise, ASM-deficient mice or hepatocytes and splenocytes ex vivo manifest resistance to anti-CD95 treatment. These results provide in vivo evidence for an important physiological function of ASM in CD95-induced apoptosis.

Published
2000
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49. Role of acidic sphingomyelinase in Fas/CD95-mediated cell death.

Author

Lin, T, Genestier, L, Pinkoski, M J, Castro, A, Nicholas, S, Mogil, R, Paris, F, Fuks, Z, Schuchman, E H, Kolesnick, R N, and Green, D R

Abstract

Engagement of the Fas receptor has been reported to induce ceramide generation via activation of acidic sphingomyelinase (aSMase). However, the role of aSMase in Fas-mediated cell death is controversial. Using genetically engineered mice deficient in the aSMase gene (aSMase(-/-)), we found that thymocytes, concanavalin A-activated T cells, and lipopolysaccharide-activated B cells derived from both aSMase(-/-) and aSMase(+/+) mice were equally sensitive to Fas-mediated cell death, triggered by either anti-Fas antibody or Fas ligand in vitro. Similarly, activation-induced apoptosis of T lymphocytes was unaffected by the status of aSMase, and aSMase(-/-) mice failed to show immunological symptoms seen in animals with defects in Fas function. In vivo, intravenous injection of 3 microg/25 g mouse body weight of anti-Fas Jo2 antibody into aSMase(-/-) mice failed to affect hepatocyte apoptosis or mortality, whereas massive hepatocyte apoptosis and animal death occurred in wild type littermates. Animals heterozygous for aSMase deficiency were also significantly protected. Susceptibility of aSMase(-/-) mice to anti-Fas antibody was demonstrated with higher antibody doses (>/=4 microg/25 g mouse). These data indicate a role for aSMase in Fas-mediated cell death in some but not all tissues.

Published
2000

50. CD95(Fas/APO-1) signals ceramide generation independent of the effector stage of apoptosis.

Author

Grullich, C, Sullards, M C, Fuks, Z, Merrill, A H, and Kolesnick, R

Abstract

Although numerous studies document caspase-independent ceramide generation preceding apoptosis upon environmental stress, the molecular ordering of ceramide generation during cytokine-induced apoptosis remains uncertain. Here, we show that CD95-induced ceramide elevation occurs during the initiation phase of apoptosis. We titrated down the amount of FADD transfected into HeLa and 293T cells until it was insufficient for apoptosis, although cycloheximide (CHX) still triggered the effector phase. Even in the absence of CHX, ceramide levels increased rapidly, peaking at 2.7 +/- 0.2-fold of control 8 h post-transfection. Dominant negative FADD failed to confer ceramide generation or CHX-mediated apoptosis. Ceramide generation induced by FADD was initiator caspase-dependent, being blocked by crmA. Limited pro-caspase 8 overexpression also increased ceramide levels 2.7 +/- 0.2-fold, yet failed, without CHX, to initiate apoptosis. Expression of membrane-targeted oligomerized CD-8 caspase 8 induced apoptosis without CHX, yet elevated ceramide only to a level equivalent to limited pro-caspase 8 transfection. Ceramide elevations were detected concurrently by diacylglycerol kinase and electrospray tandem mass spectrometry. These investigations provide evidence that ceramide generation is initiator caspase-dependent and occurs prior to commitment to the effector phase of apoptosis, definitively ordering ceramide as proximal in CD95 signaling.

Published
2000

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