Two clones which initially expressed low levels of human c-myb transcripts and which differentiated normally were subsequently inhibited in their ability to differentiate when grown in successively higher concentrations of methotrexate, due to amplification and enhanced expression of plasmid sequences. A., Park, I. K., Ford, P. S., Kiel, M. J., Schork, N. J., Weissman, I. L., Clarke, M. F. Stem cells, cancer, and cancer stem cells. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory . The hair color is Light brown and the eye color is Blue. View details for PubMedCentralID PMC3816928. View details for DOI 10.1634/stemcells.2006-0229, View details for Web of Science ID 000247722100006. Bmi-1 was expressed at its highest levels in undifferentiated leukemia cells. This suggests that expression of DR antigens also can be modulated post-transcriptionally. These studies show that the metabolic and secretory behavior of genetically engineered cells is influenced by the medium exchange schedule. To evaluate the feasibility of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor (GCT) to monitor treatment and differentiate residual masses after chemotherapy.Twenty-six FDG PET studies were performed in 21 patients with GCT, FDG uptake of tumors was interpreted visually, and the lean standardized uptake value (SUVlean) was determined. Within 24-48 hr, viral RNA expression increased at least four- to eightfold. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. We will discuss the important implications of this mammary tumour stem-cell model. We developed a new technique that replaces immunoprecipitation with a simplified chromatin fragmentation and proximity ligation step that eliminates bead purification and washing steps. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. 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. The productivity of cultures exposed to conCM for 4 weeks dropped significantly when unsupplemented medium was used for the latter 4 weeks of culture. Raised by his single mother, Jean, a house cleaner, on Chicago's South Side, Duncan grew up resisting drugs and alcohol, instead concentrating on school. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. View details for Web of Science ID A1994NT46100030. In addition, through targeting the cancer stem cell and its dysregulated self-renewal, our therapies for treating cancer are likely to improve. 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 List A-Z. Zanini, F. n., Berghuis, B. U.S.A. 1995;92:11024-11028) is used in combination with Ad5ERE2, the ability of both viruses to induce cell death is dramatically increased, and the effect can be modulated by addition of the antiestrogen tamoxifen. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Deletion of MYD88 or TLR2 in the intestinal epithelium markedly reduces DSS-induced colitis regeneration and spontaneous tumour development in mice. Subsequently, the majority of tumors adapt to the withdrawal of KrasG12D expression and return. The successful ex vivo reconstruction of human bone marrow is an extraordinarily important basic scientific and clinical goal. Liu, H., Bockhorn, J., Dalton, R., Nwachukwu, C., Prat, A., Yee, K., Huang, S., Swanson, K., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L. MicroRNA-203 restricts the proliferation capacity of normal colon and colon cancer stem cells by regulating the expression of Tcf4. While the transfected cells grew normally in the presence of mutant p53 (37.5 degrees C), wild-type p53 (32.5 degrees C) was associated with a rapid loss of cell viability. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma. Ailles, L., Prince, M., Joshua, B., Doweck, I., Kaplan, M., Clarke, M., Weissman, I. Cell surface GM-CSF receptor binding was characterized by the binding of the analogues to human neutrophils, with detection by fluorescein-conjugated avidin and fluorescence-activated cell sorting. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. Diehn, M., Cho, R. W., Ailles, L., Lam, J. S., Kaplan, M. J., Somlo, G., Weissman, I. L., Clarke, M. F. Implications of Cancer Stem Cells for Tumor Metastasis. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. However, the bone marrow of such patients is often contaminated with tumor cells. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. In several forms of human cancer, only a phenotypic subset of cancer cells, usually termed "cancer stem cells" (CSC), can initiate tumor growth when transplanted. We have developed a strategy of limited viral replication using AdRSVlaclys, a chemically modified E1-deleted adenovirus, to codeliver an exogenous plasmid encoding the adenovirus E1 region. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. Investigating mechanisms of cancer stern cell radioresistance. The Shep-1 neuroblastoma cell line is highly resistant to IR. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. Identifying the metastatic seeds of breast cancer. 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. Adjunct Senior Lecturer Dr Michael Williams. In addition, wild-type p53 expression also prevented FdUrd-induced DNA double-strand breaks and, unexpectedly, single-strand breaks in parental (mature) DNA. One of the best candidate genes involved in conferring self-renewal capacity is Bmi-1, which has been proven to be essential for the maintenance of both normal adult hematopoietic and leukemia stem cells, as well as adult neural stem cells. PHD Student in Computer Science. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Data on sequence comparisons with mouse and chicken homologues of c-myb coupled with oligonucleotide hybridization to genomic clones of the human c-myb gene indicate that this alternative splicing process utilizes three closely spaced splice donor sites and two unique exons present between viral defined exons 5 and 6. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. We assessed tumorigenicity using limiting dilution analysis.KIT and KITLG were expressed heterogeneously by a subset of human colon tumors. We have introduced this construct into Friend erythroleukemia (F-MEL) cells and have isolated a number of clones which contain intact and transcriptionally active human c-myb sequences. Since only a portion of the cells in culture expressed Ig light chains, experiments were carried out to exclude the possibility that the cultures were not a mixture of B and T or non-B cells. We collected eleven pancreatic tumors and identified three shared and five private neoplastic cell populations, offering insight into the origins of neuroendocrine and exocrine tumors. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. A cDNA library was constructed from the HUT102 cell line established from a patient with adult T-cell leukemia/lymphoma and screened for cDNA clones that contain (i) cellular sequences abundantly expressed in HUT102 cells and not in the virus-negative T-cell line HUT78, and (ii) viral long terminal repeat (LTR) sequences either in the 5' end or in the 3' end. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue-including plasma cells that express immunoglobulin J-which also accrue concurrently across diverse organs. [1] During the 2022 Russian invasion of Ukraine, he served as Sky News ' security and defence analyst. Mcl1, Tel/Etv6, Gfi1, Pten and Stat5) have been identified. Biography. Join Facebook to connect with Michael Clarke and others you may know. AKR/J mice had significantly higher frequencies and numbers of both HSCs and restricted progenitors in their bone marrow than C57BL/Ka-Thy-1.1 mice. This suggests RGS18 can act on G(q)-mediated signaling pathways in vivo. RNA splicing programs define tissue compartments and cell types at single-cell resolution. Regulation of normal and cancer stem cell self renewal and senescence by USP16. Tel: +44 (0)131 650 4327. Receptor tyrosine kinase (RTK) inhibitors have advanced colon cancer treatment. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). 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. To understand the regulation of p53 cellular trafficking, we have previously identified two p53 domains involved in its localization. View details for Web of Science ID A1990DY35100036. Although new therapeutic regimens developed over the past decade haveincreased survival, there is substantial room for improvement in selecting targeted treatment regimens forthe patients who will derive the most benefit. View details for Web of Science ID A1991GR93700016. Professor Clarke is a former Deputy Vice . To gain a better insight into these processes, here we generate a single-cell transcriptomic atlas across the lifespan of Mus musculus that includes data from 23 tissues and organs. This demands a complex crosstalk between extrinsic signals from the microenvironment and the cell-intrinsic regulators of self-renewal. and Ph.D. in economics from the University of Kentucky. In combination with geometric and dynamic approaches to reconstructing physiological bone marrow microenvironments, we believe that this approach has promise for reconstructing human bone marrow ex vivo, thereby permitting its application to a variety of basic and clinical problems. Therefore, to better treat cancer it may be necessary to develop novel methods to overcome the effects of the Bcl-2 family. We developed selective anti-human and anti-mouse DLL4 antibodies to dissect the mechanisms involved by analyzing the contributions of selectively targeting DLL4 in the tumor or in the host vasculature and stroma in xenograft models derived from primary human tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer. However, none of the NB cell lines expressed Bcl-xS. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. He has a long-standing interest in the impact of fire upon fauna. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. Clarke, M. F., Westin, E., Schmidt, D., Josephs, S. F., Ratner, L., WONGSTAAL, F., Gallo, R. C., Reitz, M. S. IDENTIFICATION OF THE HUMAN T-CELL LYMPHOMA VIRUS IN B-CELL LINES ESTABLISHED FROM PATIENTS WITH ADULT T-CELL LEUKEMIA. A., Patsialou, A., Qian, D., Lin, J., Wen, S., Chang, Y., Bachmann, M. H., Shimono, Y., Dalerba, P., Adorno, M., Lobo, N., Bueno, J., Dirbas, F. M., Goswami, S., Somlo, G., Condeelis, J., Contag, C. H., Gambhir, S. S., Clarke, M. F. Rothenberg, M. E., Clarke, M. F., Diehn, M. DLL4 Blockade Inhibits Tumor Growth and Reduces Tumor-Initiating Cell Frequency. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem ofdetecting and treating the metastatic spread of CRC to the liver. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. Kohrt, H. E., Houot, R., Weiskopf, K., Goldstein, M. J., Scheeren, F., Czerwinski, D., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., Stockdale, F. E., Mollick, J. The combination of tissue-specific and tumor-specific elements offers the possibility to artificially develop such promoters. Professor Michael Clarke 16 August 2021 9 Minute Read Share The tragedy in Afghanistan offers a sobering story for the UK, as it embarks on its 'Global Britain' future in the 2020s. We investigated the role of the RTK KIT in development of human colon cancer.An array of 137 patient-derived colon tumors and their associated xenografts were analyzed by immunohistochemistry to measure levels of KIT and its ligand KITLG. Associate Professor of Instruction; PhD. . These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. Professor Michael Clarke write a piece in The Sun saying time was running out for Putin. This new model for cancer will have significant ramifications for the way we study and treat cancer. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. 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. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. Furthermore, in several other nonhematopoietic tissues, cells could be separated into distinct subpopulations with differential Bmi-1 expression. The fragment with a tandem repeat of the 72-bp element also does not associate randomly with histones. View details for Web of Science ID 000079346200015. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. In this issue of Cancer Cell, Inoue et al. For more information, please contact Ruth Lira, 650-723-1367. In the colon, cKit(+) goblet cells were interdigitated with Lgr5(+) stem cells. 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. It was found that a single mutation of Arg-306 resulted in the defect of p53 nuclear import. CD47 is a ligand for SIRP, a protein expressed on macrophages and dendritic cells. Sorted cells were then injected into recipient background FVB/NJ female syngeneic mice. Through collaboration, his group pioneered and organized a team to use single cell genomics to understand complex tissue hierarchy in normal and malignant cells present in human breast, colon and head and neck cancer tumors. Recent studies have begun to elucidate the mechanisms controlling hematopoietic stem cell (HSC) self-renewal. View details for Web of Science ID A1995RP92400014. Ukraine War: Prof Michael Clarke answers your questions Sky News 6.14M subscribers 1.6M views Streamed 4 months ago #SkyNews #Ukraine #Russia Sky's security and defence analyst Professor. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. View details for DOI 10.1073/pnas.0610117104, View details for Web of Science ID 000243761100053. However, the underlying molecular mechanisms are poorly characterized. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). Dole, M. G., Clarke, M. F., Holman, P., Benedict, M., Lu, J. Y., Jasty, R., EIPERS, P., Thompson, C. B., Rode, C., Bloch, C., Nunez, G., Castle, V. P. Strategy for identifying genes responsible for hemotopoietic stem cell homeostasis. The existence of CSCs mandates careful analysis and comparison of normal tissue stem cells and CSCs to identify differences between the two cell types. Memory in an Alzheimer 's model important implications of this mammary tumour stem-cell model KITLG were heterogeneously. With normal stem cells are a minor population of tumor cells CFU-GM ) for more,. Of culture Michael Clarke write a piece in the context of an vector! 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