professor michael clarke biographyewu first day of classes fall 2021

It is clear that new approaches are needed to treat these diseases. Wu, A. R., Hiatt, J. Previous groups have shown that CD24medCD49fhigh cells enriched for long-lived mammary epithelial cells can be serially transplanted.METHODS: Flow cytometry-based enrichment of distinct phenotypic populations was assessed for their gene expression profiles and functional proliferative attributes in vitro and in vivo.RESULTS: Here, we show Thy-1 is differentially expressed in the CD24medCD49fhigh population, which allowed us to discern two functionally different populations. Pulse induction of p53 alone did not affect Shep-1 cell viability, while induction of p53, followed by IR, resulted in cell death and DNA fragmentation proportional to the dose of IR and the level of p53 expression. Differential regulation of medium versus serum perfusion demonstrated that increased NIH-3T3 cell metabolism was directly proportional to the serum flux to which the cells were exposed. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Many of these mutations affect cell proliferation and survival. Discover Michael Clarke 's Biography, Age, Height, Physical Stats, Dating/Affairs, Family and career updates. Previous studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis. View details for DOI 10.1146/annurev.med.58.062105.204854, View details for Web of Science ID 000244461500018, View details for Web of Science ID 000242973400002, View details for Web of Science ID 000242440001597. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. James Mallet (* 1955), Evolutionsbiologe und Entomologe. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.). Liu, H., Bockhorn, J., Dalton, R., Chang, Y., Qian, D., Zitzow, L. A., Clarke, M. F., Greene, G. L. Identification of miRNAs that regulate breast cancer stem cells and spontaneous metastases in orthotopic mouse models. and Ph.D. in economics from the University of Kentucky. The Bcl-2 family of proteins: regulators of cell death and survival. van Weele, L. J., Djomehri, S. I., Cai, S., Antony, J., Sikandar, S. S., Qian, D., Ho, W. H., West, R., Scheeren, F. A., Clarke, M. F. Publisher Correction: Cell types of origin of the cell-free transcriptome. According to a story Tom Hanks told at. We compared commercially available single-cell RNA amplification methods with both microliter and nanoliter volumes, using sequence from bulk total RNA and multiplexed quantitative PCR as benchmarks to systematically evaluate the sensitivity and accuracy of various single-cell RNA-seq approaches. Although initial adhesion of hematopoietic cells was improved by the presence of both ECMs, the overall progenitor and nonadherent cell productivity was not improved nor did the stroma grow to confluency faster. View details for DOI 10.1053/j.gastro.2015.05.042, View details for Web of Science ID 000360269800039, View details for PubMedCentralID PMC4550533. Professor William Clarke. View details for Web of Science ID A1983RE64300046. Westin, E. H., Gorse, K. M., Clarke, M. F. THE PROLIFERATION OF AML-193 IS REGULATED BY MULTIPLE HEMATOPOIETIC GROWTH-FACTORS AND CYTOKINES. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. The downstream effectors of TLR2 are expressed by normal intestinal and mammary epithelia, including the stem/progenitor cells. Other mutations between Arg-306 and NLS I have no effect on the nuclear import of p53. And while one former spy chief predicted that Putin would eventually be replaced by someone more "extreme", professor Michael Clarke, former director-general of the Royal United Services. View details for Web of Science ID 000345638500001, View details for DOI 10.1158/1538-7445.AM2014-SY12-04, View details for Web of Science ID 000349910205454, View details for Web of Science ID 000351670400001. Control experiments show that positioning is not due to the 21-bp repeats or to end effects. View details for Web of Science ID 000079323200036. 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. This transcriptomic atlas-which we denote Tabula Muris Senis, or 'Mouse Ageing Cell Atlas'-provides molecular information about how the most important hallmarks of ageing are reflected in a broad range of tissues and cell types. Prior to that he was Professor of Defence Studies at King's College London, and Deputy Vice-Principal for Research Development. Effect of ASXL1 on the stemness of colorectal cancer initiating cells. Michael W. Clark is the Director of the Center for Business and Economic Research and an Associate Professor of Economics at the University of Kentucky's Gatton College of Business and Economics. View details for DOI 10.1158/0008-5472.CAN-06-2030, View details for Web of Science ID 000244137300026. The simulation demonstrates that removal of stem cells is a possible mechanism leading to culture decline. Clarke, M. F., Trainor, C. D., Mann, D. L., Gallo, R. C., Reitz, M. S. TRANSFORMING POTENTIAL OF HUMAN C-SIS NUCLEOTIDE-SEQUENCES ENCODING PLATELET-DERIVED GROWTH-FACTOR. Cells that were kept density arrested at 32.5 degrees C (G0) lost viability at a much slower rate than did cells released into G1. Testicular cancer patients refractory or in relapse after primary chemotherapy have < or =25% 5-year progression-free survival with salvage. 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. 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. Frequently, overexpression of a member of the Bcl-2 family results in a block in cell death and appears to nullify many built-in cellular defense mechanisms against cancer. 29 Oxford St, Pierce 229. jaiz@seas.harvard.edu (617) 495-3558. 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. Solid CRC tissues, either primary tissues collected from surgical specimens or xenografts established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into single-cell suspensions and analyzed by flow cytometry. Although neither the visual interpretation nor SUVlean differentiated mature teratoma from necrosis or scar, there were statistically significant differences in the kinetic rate constants K1 and K between mature teratoma and necrosis or scar as follows: K1, 0.113 mL/min/g +/- 0.026 versus 0.036 mL/min/g +/- 0.005 (P < .05); K, 0.005 mL/min/g +/- 0.003 versus 0.0008 mL/min/g +/- 0.0001 (P < .05).FDG PET with kinetic analysis appears to be a promising method for management of disease in patients with GCT after treatment. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. Dr. Jim Clarke is an Adjunct Professor of Civil and Environmental Engineering and an Adjunct Professor of Earth and Environmental Sciences at Vanderbilt University. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Professor Michael Clarke was Director General of the Royal United Services Institute (RUSI) from 2007 to 2015. Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. Transformation is a complex cellular process that requires several genetic abnormalities. Using single-cell transcriptomic data, we assessed cell-type-specific manifestations of different hallmarks of ageing-such as senescence3, genomic instability4 and changes in the immune system2. 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. Park, I. K., He, Y. Q., Lin, F. M., Laerum, O. D., Tian, Q., Bumgarner, R., Klug, C. A., Li, K. J., Kuhr, C., Doyle, M. J., Xie, T., Schummer, M., Sun, Y., GOLDSMITH, A., Clarke, M. F., Weissman, I. L., Hood, L., Li, L. H. A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. (2007) analyze the relationship between CSC and tumor metastasis. A novel regulator of G-protein signaling (RGS) has been isolated from a highly purified population of mouse long-term hematopoietic stem cells, and designated RGS18. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. X-ray irradiated cells expressing wtp53 displayed microscopic and biochemical characteristics consistent with cell death due to apoptosis. Search by Name. Bmi-1 was expressed at its highest levels in undifferentiated leukemia cells. View details for DOI 10.1186/s13058-018-1006-y, View details for Web of Science ID 000447203300001, View details for Web of Science ID 000440602000145, View details for Web of Science ID 000440602000051, View details for DOI 10.1200/JCO.2018.36.4_suppl.683, View details for Web of Science ID 000436174100659. 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. Liu, T. X., Becker, M. W., Jelinek, J., Wu, W., Deng, M., Mikhalkevich, N., Hsu, K., Bloomfield, C. D., Stone, R. M., DeAngelo, D. J., Galinsky, I. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. Hosen, N., Clarke, M. F., Weissman, I. L. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. View details for Web of Science ID A1996UG75600003. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype. We assessed tumorigenicity using limiting dilution analysis.KIT and KITLG were expressed heterogeneously by a subset of human colon tumors. Cell lines were established from the peripheral blood of two patients with adult T cell leukemia. Leukemic peripheral blood lymphocytes from individuals infected with the human T-cell leukemia/lymphoma virus (HTLV) were found to express little or no viral RNA before being put into tissue culture. Lobo, N., Zabala, M., Qian, D., Clarke, M. F. The DLK1-DIO3 imprinted region regulates long-term proliferation in normal and malignant breast epithelium. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. Tumors originated from EpCAM(high)/CD44+ cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. This apparent paradox is the focus of our interest. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells.We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Reitz, M. S., Mann, D., Clarke, M. F., Kalyanaraman, V. S., Robert-Guroff, M., Popovic, M., Gallo, R. C. HOMOLOGY OF HUMAN T-CELL LEUKEMIA-VIRUS ENVELOPE GENE WITH CLASS-I HLA-GENE. Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. The induced p53 is functional as p53-responsive genes (Waf-1 and MDM-2) are appropriately induced following IR. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., Weissman, I. L., Clarke, M. F., Ailles, L. E. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. A growing body of evidence indicates that subpopulations of cancer stem cells (CSCs) drive and maintain many types of human malignancies. Analysis of DNase I cutting of uniquely end-labeled complexes suggests that the fragment containing a single 72-bp element forms a positioned core particle. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. . Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Tumor kinetic rate constants (K1, k2, k3) and net rate of FDG phosphorylation (K = [K1.k3]/[k2 + k3]) in tumors were calculated from the dynamic data by means of a three-compartment model, assuming k4 = 0.Viable tumors (n = 10) showed intense FDG uptake and could easily be differentiated visually from mature teratoma (n = 6) and necrosis or scar (n = 10). View details for DOI 10.1146/annurev.cellbio.22.010305.104154, View details for Web of Science ID 000250896200025. Furthermore, we identify unique, CSC-specific, remodeling events. View details for DOI 10.1038/s41587-021-01188-9, View details for DOI 10.7554/eLife.70692.sa2, View details for Web of Science ID 000715795700001, View details for Web of Science ID 000680263504041, View details for DOI 10.1200/JCO.2021.39.15_suppl.e15067, View details for Web of Science ID 000708120301134, View details for DOI 10.1200/JCO.2021.39.15_suppl.3105, View details for Web of Science ID 000708120601279. These results suggest that radiation-induced cell death occurs by both p53-dependent and p53-independent pathways. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory . The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). An in vivo reconstitution assay revealed that the frequency of HSCs was 1/16 in Bmi-1high c-kit+ lin -Sca-1+ bone marrow (BM) cells and 1/49 in Bmi-1 high lin- BM cells, suggesting that Bmi-1 may serve as a marker for normal HSCs. Zabala, M., Lobo, N. A., Seoane, J. Replication-defective retroviruses are frequently used as gene carriers for gene transfer into target cells. Furthermore, in several other nonhematopoietic tissues, cells could be separated into distinct subpopulations with differential Bmi-1 expression. We have designed a microfluidic device to perform sensitive ChIP analysis on low cell numbers in a rapid, automated fashion while preserving the specificity of the assay. Major conclusions of the symposium were that the flow cytometry of multiple markers in fresh tissue would remain the standard technique of evaluating cancer-initiating cells and that surrogates need to be developed for both experimental and clinical use. 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. Advances in our understanding of apoptosis has identified the Bcl-2 family as a mediator of most apoptosis pathways, including those initiated by oncogenes, tumor suppressor genes, growth factor withdrawal, and external damaging signals. He served as the Head of the School of Life Sciences from 2011-2019. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. 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. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. In addition to his clinical duties in the division of Oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and their malignant counterparts; and ii) the identification and characterization of cancer stem cells. Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. View details for Web of Science ID A1997YA26800007. We then determined the effects of intratumoral injection of bcl-xs adenovirus on solid MCF-7 tumors in nude mice. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. In bone marrow, RGS18 level is highest in long-term and short-term hematopoietic stem cells, and is decreased as they differentiate into more committed multiple progenitors. War in Ukraine 2022: Prof. Michael Clarke analysis 116 videos 3,380 views Updated 5 days ago Defence and security analyst Professor Michael Clarke's observations mostly on Sky News. It has 234 amino acids consisting of a central RGS box and short divergent NH(2) and COOH termini. Prior to coming to UK, Dr. Clark was the Chief Economist for the Kentucky Legislative Research . We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. CHUCK, A. S., Clarke, M. F., Palsson, B. O. bcl-x(s) gene therapy induces apoptosis of human mammary tumors in nude mice. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. He also carries out research into the cellular responses to anti-cancer drugs. Northstar is a useful tool to assign known and novel cell type and states in the age of cell atlases. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. The Shep-1 neuroblastoma cell line is highly resistant to IR. We present a simple single tube proximity ligation technique, targeted chromatin ligation, that captures histone modification patterns with only 200 cells. Four major epithelial subtypes or transcriptional states were revealed by gene expression analysis of selected populations of single cells. Although wild-type p53 is expressed in virtually all neuroblastoma tumors, treatment failures secondary to inadequate local control with radiotherapy are a problem in patients with advanced stage disease. We demonstrate that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems. Assign known and novel cell type and states in the Age of cell atlases and Regenerative Medicine 3T3! Was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect Bmi-1-/-! 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