Search

Your search keyword '"Mallon, Barbara S."' showing total 46 results
Start Over Author "Mallon, Barbara S."
46 results on '"Mallon, Barbara S."'

21. CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit

Author

Lee, Chun-Ting, primary, Chen, Jia, additional, Kindberg, Abigail A, additional, Bendriem, Raphael M, additional, Spivak, Charles E, additional, Williams, Melanie P, additional, Richie, Christopher T, additional, Handreck, Annelie, additional, Mallon, Barbara S, additional, Lupica, Carl R, additional, Lin, Da-Ting, additional, Harvey, Brandon K, additional, Mash, Deborah C, additional, and Freed, William J, additional

Published
2016
Full Text
View/download PDF

26. Functional Consequences of 17q21.31/WNT3-WNT9B Amplification in hPSCs with Respect to Neural Differentiation

Author

Lee, Chun-Ting, primary, Bendriem, Raphael M., additional, Kindberg, Abigail A., additional, Worden, Lila T., additional, Williams, Melanie P., additional, Drgon, Tomas, additional, Mallon, Barbara S., additional, Harvey, Brandon K., additional, Richie, Christopher T., additional, Hamilton, Rebecca S., additional, Chen, Jia, additional, Errico, Stacie L., additional, Tsai, Shang-Yi A., additional, Uhl, George R., additional, and Freed, William J., additional

Published
2015
Full Text
View/download PDF

28. Directed Differentiation of Human Induced Pluripotent Stem Cells Toward Bone and Cartilage: In Vitro Versus In Vivo Assays

Author

Phillips, Matthew D., primary, Kuznetsov, Sergei A., additional, Cherman, Natasha, additional, Park, Kyeyoon, additional, Chen, Kevin G., additional, McClendon, Britney N., additional, Hamilton, Rebecca S., additional, McKay, Ronald D.G., additional, Chenoweth, Josh G., additional, Mallon, Barbara S., additional, and Robey, Pamela G., additional

Published
2014
Full Text
View/download PDF

30. Regulation and Expression of the ATP-Binding Cassette Transporter ABCG2 in Human Embryonic Stem Cells

Author

Padmanabhan, Raji, primary, Chen, Kevin G., additional, Gillet, Jean-Pierre, additional, Handley, Misty, additional, Mallon, Barbara S., additional, Hamilton, Rebecca S., additional, Park, Kyeyoon, additional, Varma, Sudhir, additional, Mehaffey, Michele G., additional, Robey, Pamela G., additional, McKay, Ronald D. G., additional, and Gottesman, Michael M., additional

Published
2012
Full Text
View/download PDF

31. CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit

Author

Lee, Chun-Ting, Chen, Jia, Kindberg, Abigail A, Bendriem, Raphael M, Spivak, Charles E, Williams, Melanie P, Richie, Christopher T, Handreck, Annelie, Mallon, Barbara S, Lupica, Carl R, Lin, Da-Ting, Harvey, Brandon K, Mash, Deborah C, and Freed, William J

Abstract

Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies.

Published
2017
Full Text
View/download PDF

35. Functional Consequences of 17q21.31/WNT3-WNT9BAmplification in hPSCs with Respect to Neural Differentiation

Author

Lee, Chun-Ting, Bendriem, Raphael M., Kindberg, Abigail A., Worden, Lila T., Williams, Melanie P., Drgon, Tomas, Mallon, Barbara S., Harvey, Brandon K., Richie, Christopher T., Hamilton, Rebecca S., Chen, Jia, Errico, Stacie L., Tsai, Shang-Yi A., Uhl, George R., and Freed, William J.

Abstract

Human pluripotent stem cell (hPSC) lines exhibit repeated patterns of genetic variation, which can alter in vitro properties as well as suitability for clinical use. We examined associations between copy-number variations (CNVs) on chromosome 17 and hPSC mesodiencephalic dopaminergic (mDA) differentiation. Among 24 hPSC lines, two karyotypically normal lines, BG03 and CT3, and BG01V2, with trisomy 17, exhibited amplification of the WNT3/WNT9Bregion and rapid mDA differentiation. In hPSC lines with amplified WNT3/WNT9B, basic fibroblast growth factor (bFGF) signaling through mitogen-activated protein kinase (MAPK)/ERK amplifies canonical WNT signaling by phosphorylating LRP6, resulting in enhanced undifferentiated proliferation. When bFGF is absent, noncanonical WNT signaling becomes dominant due to upregulation of SIAH2, enhancing JNK signaling and promoting loss of pluripotency. When bFGF is present during mDA differentiation, stabilization of canonical WNT signaling causes upregulation of LMX1Aand mDA induction. Therefore, CNVs in 17q21.31, a “hot spot” for genetic variation, have multiple and complex effects on hPSC cellular phenotype.

Published
2015
Full Text
View/download PDF

40. The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells.

Author

Pascal Laeng, Pitts, Richard L., Lemire, Andrew L., Drabik, Christopher E., Weiner, Arin, Haiping Tang, Thyagarajan, Rathi, Mallon, Barbara S., and Altar, C. Anthony

Subjects
MOOD (Psychology), VALPROIC acid, ACETIC acid, DEVELOPMENTAL neurobiology, EMBRYOLOGY, PROSENCEPHALON, LABORATORY rats
Abstract

Valproate, an anticonvulsant drug used to treat bipolar disorder, was studied for its ability to promote neurogenesis from embryonic rat cortical or striatal primordial stem cells. Six days of valproate exposure increased by up to fivefold the number and percentage of tubulinβ III-immunopositive neurons, increased neurite outgrowth, and decreased by fivefold the number of astrocytes without changing the number of cells. Valproate also promoted neuronal differentiation in human fetal forebrain stem cell cultures. The neurogenic effects of valproate on rat stem cells exceeded those obtained with the neurotrophins brain-derived growth factor (BDNF) or NT-3, and slightly exceeded the effects obtained with another mood stabilizer, lithium. No effect was observed with carbamazepine. Most of the newly formed neurons were GABAergic, as shown by 10-fold increases in neurons that immunostained for GABA and the GABA-synthesizing enzyme GAD65/67. Double immunostaining for bromodeoxyuridine and tubulinβ III showed that valproate increased by four- to fivefold the proliferation of neuronal progenitors derived from rat stem cells and increased cyclin D2 expression. Valproate also regulated the expression of survival genes, Bad and Bcl-2, at different times of treatment. The expression of prostaglandin E synthase, analyzed by quantitative RT-PCR, was increased by ninefold as early as 6 h into treatment by valproate. The enhancement of GABAergic neuron numbers, neurite outgrowth, and phenotypic expression via increases in the neuronal differentiation of neural stem cell may contribute to the therapeutic effects of valproate in the treatment of bipolar disorder. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

41. Regulation and Expression of the ATP‐Binding Cassette TransporterABCG2 in Human Embryonic Stem Cells

Author

Padmanabhan, Raji, Chen, Kevin G., Gillet, Jean‐Pierre, Handley, Misty, Mallon, Barbara S., Hamilton, Rebecca S., Park, Kyeyoon, Varma, Sudhir, Mehaffey, Michele G., Robey, Pamela G., McKay, Ronald D. G., and Gottesman, Michael M.

Abstract

The expression and function of several multidrug transporters (including ABCB1 and ABCG2) have been studied in human cancer cells and in mouse and human adult stem cells. However, the expression of ABCG2 in human embryonic stem cells (hESCs) remains unclear. Limited and contradictory results in the literature from two research groups have raised questions regarding its expression and function. In this study, we used quantitative real‐time PCR, Northern blots, whole genome RNA sequencing, Western blots, and immunofluorescence microscopy to study ABCG2expression in hESCs. We found that full‐length ABCG2mRNA transcripts are expressed in undifferentiated hESC lines. However, ABCG2 protein was undetectable even under embryoid body differentiation or cytotoxic drug induction. Moreover, surface ABCG2 protein was coexpressed with the differentiation marker stage‐specific embryonic antigen‐1 of hESCs, following constant BMP‐4 signaling at days 4 and 6. This expression was tightly correlated with the downregulation of two microRNAs (miRNAs) (i.e., hsa‐miR‐519c and hsa‐miR‐520h). Transfection of miRNA mimics and inhibitors of these two miRNAs confirmed their direct involvement in the regulation ABCG2 translation. Our findings clarify the controversy regarding the expression of the ABCG2gene and also provide new insights into translational control of the expression of membrane transporter mRNAs by miRNAs in hESCs. STEMCells2012;30:2175–2187

Published
2012
Full Text
View/download PDF

42. CONTROL OF THE MYELIN PROTEOLIPID PROTEIN GENE BY RNA STABILITY IN CULTURED CELLS.

Author

Mallon, Barbara S. and Macklin, Wendy B.

Subjects
*GENES, *CELLS, *GENE expression, *RNA
Abstract

The article presents an abstract related to the control of myelin proteolipid protein gene by stability in cultured cells. mRNA stability influences gene expression in organisms as diverse as bacteria and mammals. The abundance of a particular RNA in mammalian cells may fluctuate manyfold due to a change in mRNA half-life without any change in the transcription rate.

Published
1999

43. Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein.

Author

Haiying Qin, Cho, Monica, Haso, Waleed, Ling Zhang, Tasian, Sarah K., Htoo Zarni Oo, Negri, Gian Luca, Yongshun Lin, Jizhong Zou, Mallon, Barbara S., Maude, Shannon, Teachey, David T., Barrett, David M., Orentas, Rimas J., Daugaard, Mads, Sorensen, Poul H. B., Grupp, Stephan A., and Fry, Terry J.

Subjects
*T cells, *ANTIGEN receptors, *THYMIC stromal lymphopoietin, *CYTOKINES, *LEUKEMIA, *CELL lines
Abstract

Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting the CD19 B cell-associated protein have demonstrated potent activity against relapsed/refractory B-lineage acute lymphoblastic leukemia (B-ALL). Not all patients respond, and CD19-negative relapses have been observed. Overexpression of the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2) occurs in a subset of adults and children with B-ALL and confers a high risk of relapse. Recent data suggest the TSLPR signaling axis is functionally important, suggesting that TSLPR would be an ideal immunotherapeutic target. We constructed short and long CARs targeting TSLPR and tested efficacy against CRLF2-overexpressing B-ALL. Both CARs demonstrated activity in vitro, but only short TSLPR CAR T cells mediated leukemia regression. In vivo activity of the short CAR was also associated with long-term persistence of CAR-expressing T cells. Short TSLPR CAR treatment of mice engrafted with a TSLPR-expressing ALL cell line induced leukemia cytotoxicity with efficacy comparable with that of CD19 CAR T cells. Short TSLPR CAR T cells also eradicated leukemia in 4 xenograft models of human CRLF2-overexpressing ALL. Finally, TSLPR has limited surface expression on normal tissues. TSLPR-targeted CAR T cells thus represent a potent oncoprotein-targeted immunotherapy for high-risk ALL. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

44. Resistance to Naïve and Formative Pluripotency Conversion in RSeT Human Embryonic Stem Cells.

Author

Chen KG, Johnson KR, Park K, Maric D, Yang F, Liu WF, Fann YC, Mallon BS, and Robey PG

Abstract

One of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naïve pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naïve protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent hypoxic growth conditions as required by naïve hESCs, in which some RSeT cells (e.g., H1 cells) exhibit much lower single cell plating efficiency, having altered or much retarded cell growth under both normoxia and hypoxia. Evidently, hPSCs lack many transcriptomic hallmarks of naïve and formative pluripotency (a phase between naive and primed states). Integrative transcriptome analysis suggests our primed and RSeT hESCs are close to the early stage of post-implantation embryos, similar to the previously reported primary hESCs and early hESC cultures. Moreover, RSeT hESCs did not express naïve surface markers such as CD75, SUSD2, and CD130 at a significant level. Biochemically, RSeT hESCs exhibit a differential dependency of FGF2 and co-independency of both Janus kinase (JAK) and TGFβ signaling in a cell-line-specific manner. Thus, RSeT hESCs represent a previously unrecognized pluripotent state downstream of formative pluripotency. Our data suggest that human naïve pluripotent potentials may be restricted in RSeT medium. Hence, this study provides new insights into pluripotent state transitions in vitro ., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Published
2024
Full Text
View/download PDF

45. Metabolic Quadrivalency in RSeT Human Embryonic Stem Cells.

Author

Chen KG, Park K, Maric D, Johnson KR, Robey PG, and Mallon BS

Abstract

One of the most important properties of human embryonic stem cells (hESCs) is related to their pluripotent states. In our recent study, we identified a previously unrecognized pluripotent state induced by RSeT medium. This state makes primed hESCs resistant to conversion to naïve pluripotent state. In this study, we have further characterized the metabolic features in these RSeT hESCs, including metabolic gene expression, metabolomic analysis, and various functional assays. The commonly reported metabolic modes include glycolysis or both glycolysis and oxidative phosphorylation (i.e., metabolic bivalency) in pluripotent stem cells. However, besides the presence of metabolic bivalency, RSeT hESCs exhibited a unique metabolome with additional fatty acid oxidation and imbalanced nucleotide metabolism. This metabolic quadrivalency is linked to hESC growth independent of oxygen tension and restricted capacity for naïve reprogramming in these cells. Thus, this study provides new insights into pluripotent state transitions and metabolic stress-associated hPSC growth in vitro ., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Published
2024
Full Text
View/download PDF

46. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative.

Author

Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, Beighton G, Bello PA, Benvenisty N, Berry LS, Bevan S, Blum B, Brooking J, Chen KG, Choo AB, Churchill GA, Corbel M, Damjanov I, Draper JS, Dvorak P, Emanuelsson K, Fleck RA, Ford A, Gertow K, Gertsenstein M, Gokhale PJ, Hamilton RS, Hampl A, Healy LE, Hovatta O, Hyllner J, Imreh MP, Itskovitz-Eldor J, Jackson J, Johnson JL, Jones M, Kee K, King BL, Knowles BB, Lako M, Lebrin F, Mallon BS, Manning D, Mayshar Y, McKay RD, Michalska AE, Mikkola M, Mileikovsky M, Minger SL, Moore HD, Mummery CL, Nagy A, Nakatsuji N, O'Brien CM, Oh SK, Olsson C, Otonkoski T, Park KY, Passier R, Patel H, Patel M, Pedersen R, Pera MF, Piekarczyk MS, Pera RA, Reubinoff BE, Robins AJ, Rossant J, Rugg-Gunn P, Schulz TC, Semb H, Sherrer ES, Siemen H, Stacey GN, Stojkovic M, Suemori H, Szatkiewicz J, Turetsky T, Tuuri T, van den Brink S, Vintersten K, Vuoristo S, Ward D, Weaver TA, Young LA, and Zhang W

Subjects
Alkaline Phosphatase metabolism, Antigens, CD biosynthesis, Biotechnology methods, Cell Differentiation, Cell Lineage, Cell Membrane metabolism, Cells, Cultured, Cluster Analysis, Female, Gene Expression Profiling, Genotype, Glycolipids chemistry, Humans, Membrane Glycoproteins biosynthesis, Tetraspanin 29, Embryonic Stem Cells cytology, Gene Expression Regulation, Developmental
Abstract

The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.

Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results