HSCs have the ability to self-renew, while MPP cells have lost the capacity for self-renewal. Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood. This is accompanied by a translocation of the p53 protein from the cytoplasm to the nucleus. View details for Web of Science ID 000182941000008. The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. According to a story Tom Hanks told at. DNA fragments containing either one or both of the 72-base pair (bp) elements which constitute the SV40 enhancer and the three adjacent 21-bp repeats were associated with histone octomers from chicken erythrocytes in vitro. Nuovo ateismo o neo-ateismo, anche nella grafia neoateismo (in inglese New Atheism), una corrente di pensiero che raccoglie le posizioni promosse da alcuni atei del XXI secolo. Oncolytic adenoviruses with restricted replication can be produced if the expression of crucial transcription units of the virus is controlled by tissue- or tumor-specific promoters. INGRAHAM, L. M., Weening, R. S., Clarke, M. F., Boxer, L. A., Baehner, R. L. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Directed Reading in Stem Cell Biology and Regenerative Medicine, Stem Cell Biology and Regenerative Medicine (Phd Program), DOI 10.1146/annurev.cellbio.22.010305.104154. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Adams, S., Upadhyaya, G., Clarke, M. F., Emerson, S. G. CONSTITUTIVE EXPRESSION OF A C-MYB CDNA BLOCKS FRIEND MURINE ERYTHROLEUKEMIA CELL-DIFFERENTIATION. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. However, the bone marrow of such patients is often contaminated with tumor cells. In many cases, breast cancer cells retain the expression of estrogen receptors, and most solid tumors suffer from hypoxia as a consequence of their aberrant vascularization. By examining the pathways upstream and downstream of Bmi1, hence the molecular pathways that regulate self-renewal, his laboratory found that USP16, a protein that dampens Bmi1 signals, causes a stem cell defect in various stem cells in Downs syndrome, including neural stem cells. Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Olivieri, J., Dehghannasiri, R., Wang, P. L., Jang, S., de Morree, A., Tan, S. Y., Ming, J., Wu, A., Consortium, T., Quake, S. R., Krasnow, M. A., Salzman, J. TACH101, a first-in-class pan inhibitor of KDM4 histone lysine demethylases. Metastasis remains a significant challenge in treating cancer. Professor William Clarke. Professor, Philosophy; Associate Professor, Classics npappas@gc.cuny.edu John D. Greenwood Deputy Executive Officer and Professor, Philosophy; Professor, Psychology +1 212-817-8617 jgreenwood@gc.cuny.edu Natile Clarke Assistant Program Officer, Philosophy +1 212-817-8623 nclarke@gc.cuny.edu Clarke, Clifton - Professor: Business Management Clement, Anthony E. - Associate Professor: Mathematics Cohen, Douglas - Lecturer/Doctoral Scholar: . Self-renewal requires the integration of survival signals and proliferation controls with the maintenance of an undifferentiated state. A key event in this process is the deregulation of normal self-renewal in these cells. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma. View details for DOI 10.1038/s41598-020-71805-1. View details for Web of Science ID 000166430900009. The hair color is Light brown and the eye color is Blue. This physiochemical limitation can be overcome, and effective contact between the retroviral gene carrier and the target cell can be obtained, by using net convective flow of retrovirus-containing medium through a layer of target cells. View details for DOI 10.1002/1878-0261.13220, View details for DOI 10.1038/s41587-022-01293-3. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. Evidence from studies in murine and human embryonic stem cells indicates that Polycomb group proteins play a dynamic role in concert with master transcriptional regulators in actively maintaining an undifferentiated state, suggesting that this mechanism applies to multiple types of stem cell. We show that single-cell RNA-seq can be used to perform accurate quantitative transcriptome measurement in individual cells with a relatively small number of sequencing reads and that sequencing large numbers of single cells can recapitulate bulk transcriptome complexity. Wu, A. R., Neff, N. F., Kalisky, T., Dalerba, P., Treutlein, B., Rothenberg, M. E., Mburu, F. M., Mantalas, G. L., Sim, S., Clarke, M. F., Quake, S. R. Oncogenic miRNAs and the perils of losing control of a stem cell's epigenetic identity. A., Clarke, M. F., Quake, S. R. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris3. Resolution of "averaged" innate immune responses in single IECs thus revealed unexpected heterogeneity in both the induction and subversion of early host antiviral immunity, which modulated host range. When a virus expressing the proapoptotic gene Bc1-xs (Clarke et al., Proc. Here we report that microRNA-30c, a human breast tumour prognostic marker, has a pivotal role in chemoresistance by a direct targeting of the actin-binding protein twinfilin 1, which promotes epithelial-to-mesenchymal transition. Yoo, S., Chandhasin, C., Del Rosario, J., Chen, Y. K., Stafford, J., Perabo, F., Clarke, M. F. Inhibition of histone lysine demethylases with TACH101, a first-in-class pan-inhibitor of KDM4. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. Estrogen response elements and hypoxia-responsive elements were combined to activate transcription in cells that present at least one of these characteristics. Recently, his group described a molecular mechanism that confers resistance to radiation in breast cancer stem cells. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. The cumulative data provide the foundation for an atlas of transcriptomic cell biology. MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. List A-Z. Finally, the laboratory is actively pursuing how cancer stem cells self-renew to maintain themselves and escape the genetic constraints on unlimited self-renewal that regulate normal stem cell numbers. They were introduced into the E4 region of AdEHT2 and AdEHE2F, respectively. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. Adorno, M., di Robilant, B. N., Sikandar, S. S., Acosta, V. H., Antony, J., Heller, C. H., Clarke, M. F. Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Here we describe a role for cell-intrinsic toll-like receptor-2 (TLR2; which is involved in inflammatory response) signalling in normal intestinal and mammary epithelial cells and oncogenesis. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. Chemotherapy resistance frequently drives tumour progression. Arthur Thomas Malkin (1803-1888), Pionier der Bergsteigerei und Schriftsteller. View details for DOI 10.1053/j.gastro.2015.05.042, View details for Web of Science ID 000360269800039, View details for PubMedCentralID PMC4550533. Within the colon, the Hedgehog protein signal does not act directly on the epithelium itself, but on underlying stromal cells to induce expression of IL-10, an immune-modulatory cytokine long known to suppress inflammatory intestinal damage. The weight is in Kilograms- 70 kg. Human T-cell leukaemia virus (HTLV), first isolated in the United States from a patient with cutaneous T-cell lymphoma, is a unique horizontally transmitted retrovirus which is highly associated with certain adult T-cell malignancies. The Shep-1 neuroblastoma cell line is highly resistant to IR. When viability was measured 24 h post-radiation, cells that had been briefly exposed to wtp53 immediately after X-ray irradiation had decreased survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated DP16-1 cells. Receptor tyrosine kinase (RTK) inhibitors have advanced colon cancer treatment. Murine CD18 can be expressed on the cell surface of up to 20% of the mature cells generated by the culture system, suggesting that clinically significant levels of gene transfer may be occurring. View details for Web of Science ID 000079323200036. It is likely that targeting cancer cell self-renewal pathways will result in more effective cancer therapies. View details for Web of Science ID A1984SJ97500057. The molecular mechanisms that limit the proliferation capacity of multipotent progenitors and other more mature progenitors are not fully understood. The stem cells maintain themselves through a process known as self-renewal. Patsialou, A., Bravo-Cordero, J., Wang, Y., Liu, H., Clarke, M. F., Condeells, J. S. Deregulation of stem cell self-renewal pathways in cancer, MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. View details for DOI 10.1146/annurev.cellbio.22.010305.104154, View details for Web of Science ID 000250896200025. Bcl11b(high) cells are enriched for cells that can regenerate mammary glands in secondary transplants. Kalani, M. A., Dalerba, P., Clarke, M. F., Leong, S. P. Rothenberg, M., Clarke, M. F., Lanza, R., Gearhart, J., Hogan, B., Melton, D., Pedersen, R., Thomas, E. D., Thomson, J., Wilmut, Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy. C-myb is involved in regulating normal human hematopoiesis, and inhibits dimethyl sulfoxide-induced differentiation of Friend murine erythroleukemia (F-MEL) cells. These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. We describe the construction and characterization of a hybrid promoter for transcriptional targeting of breast cancer. Rothenberg, M. E., Nusse, Y., Kalisky, T., Lee, J. J., Dalerba, P., Scheeren, F., Lobo, N., Kulkarni, S., Sim, S., Qian, D., Beachy, P. A., Pasricha, P. J., Quake, S. R., Clarke, M. F. Single-cell dissection of transcriptional heterogeneity in human colon tumors. The expression of the E1A gene in both viruses is controlled by a minimal dual-specificity promoter that responds to estrogens and hypoxia. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. View details for DOI 10.1016/j.gde.2003.11.007, View details for Web of Science ID 000188978200008. View details for DOI 10.1073/pnas.1212188109, View details for Web of Science ID 000312605600104, View details for PubMedCentralID PMC3528539. 2 Conocido por ser uno de los intrpretes ms reconocidos de Hollywood, y muchas de sus pelculas, ya sean dramas o comedias, han recibido reconocimiento internacional. Thus, these mice allow for the isolation of viable Bmi-1-expressing cells and have the potential to become a useful tool for understanding the role of Bmi-1 in normal and cancer stem cells in multiple tissue types. View details for DOI 10.1016/j.gde.2006.08.011, View details for Web of Science ID 000241320300009, View details for Web of Science ID 000238326700034. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q). The CSD could block the binding of p53 to the NLS receptor, importin alpha, and reduce the efficiency of p53 nuclear import in MCF-7, H1299, and Saos-2 cells. Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. The tight regulation of E1A expression correlated with the ability of these viruses to replicate and kill human cancer cells that express estrogen receptors, or are maintained under hypoxic conditions. The enhanced cytotoxicity was restricted to antibody-coated tumor cells. Furthermore, in several other nonhematopoietic tissues, cells could be separated into distinct subpopulations with differential Bmi-1 expression. Rachel Ellehuus. Parashurama, N., Lobo, N. A., Ito, K., Mosley, A. R., Habte, F. G., Zabala, M., Smith, B. R., Lam, J., Weissman, I. L., Clarke, M. F., Gambhir, S. S. Effect of stimulation of natural killer cells with an anti-CD137 mAb on the efficacy of trastuzumab, cetuximab, and rituximab. Zanini, F. n., Berghuis, B. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. We examined the effect of this limited adenovirus replication in vitro and in vivo. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. These tools should lead to new insights into the cellular and molecular mechanisms that drive human breast cancer growth and invasion. Professor Michael Clarke was Director General of the Royal United Services Institute from 2007-2015, where he remains a Distinguished Fellow. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. PHD Student in Computer Science. Liu, H., Shimono, Y., Bockhorn, J., Olopade, F., Greene, G., Clarke, M. F. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. FUKUNAGAJOHNSON, N., Ryan, J. J., Wicha, M., Nunez, G., Clarke, M. F. OVEREXPRESSION OF BCL-X(S), SENSITIZES MCF-7 CELLS TO CHEMOTHERAPY-INDUCED APOPTOSIS. View details for Web of Science ID 000182853100046. Professor Michael Clarke said that sending soldiers to take Kyiv was 'massively foolish' and could become a 'peak Putin' moment that leads eventually to his downfall. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. Transformation is a complex cellular process that requires several genetic abnormalities. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. View details for Web of Science ID A1984SP90200011. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. At present, neither the role that the stromal cell extra-cellular matrix (ECM) plays in influencing stroma behavior is well understood nor are the effects of stroma aging. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Sikandar, S. S., Kuo, A. H., Kalisky, T. n., Cai, S. n., Zabala, M. n., Hsieh, R. W., Lobo, N. A., Scheeren, F. A., Sim, S. n., Qian, D. n., Dirbas, F. M., Somlo, G. n., Quake, S. R., Clarke, M. F. Control of inflammation by stromal Hedgehog pathway activation restrains colitis. Natl. Okamoto, T., Reitz, M. S., Clarke, M. F., JAGODZINSKI, L. J., WONGSTAAL, F. Sequence-specific interaction of histones with the simian virus 40 enhancer region in vitro. Taken together, these results suggest that USP16 has an important role in antagonizing the self-renewal and/or senescence pathways in Down's syndrome and could serve as an attractive target to ameliorate some of the associated pathologies. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. In addition, through targeting the cancer stem cell and its dysregulated self-renewal, our therapies for treating cancer are likely to improve. We report here that the genes for HLA class I antigens are also highly methylated in the T-ALL T-cell lines relative to the same genes in the ATL T-cell lines, normal peripheral blood T cells, and autologous normal B-cell lines. Betancur, P. A., Abraham, B. J., Yiu, Y. Y., Willingham, S. B., Khameneh, F., Zarnegar, M., Kuo, A. H., McKenna, K., Kojima, Y., Leeper, N. J., Ho, P., Gip, P., Swigut, T., Sherwood, R. I., Clarke, M. F., Somlo, G., Young, R. A., Weissman, I. L. Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future Directions. View details for DOI 10.1038/s41586-022-04461-2. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression. Further investigation will reveal whether this translates to improved therapy in the future. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes. The metabolic and secretory characteristics of NIH-3T3 fibroblasts transfected with a cDNA encoding human granulocyte-macrophage colony stimulating factor (GM-CSF) were examined as a function of the culture medium exchange schedule. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Recently, various new players that regulate HSC maintenance (e.g. Therefore, infection with this virus preferentially kills estrogen receptor-positive breast cancer cells, or cells growing under hypoxic conditions. Han, J. S., Qian, D. L., Wicha, M. S., Clarke, M. F. Targeting cancer cell death with a bcl-x(s) adenovirus. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). Controlled by a minimal dual-specificity promoter that responds to estrogens and hypoxia a. Advanced colon cancer treatment maintenance ( e.g increase HSC frequencies when bred onto a C57BL background estrogen receptor-positive cancer. The Royal United Services Institute from 2007-2015, where he remains a Distinguished Fellow professor michael clarke biography the... Marrow of such patients is often contaminated with tumor cells ID 000241320300009, View details for 10.1053/j.gastro.2015.05.042... 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