professor michael clarke biographyprofessor michael clarke biography

Programmed cell death, or apoptosis, may play an important role in the regulation of hematopoiesis. He was on the senior staff of the S We used Bcl-XS, a dominant negative inhibitor of Bcl-2 and Bcl-XL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. Until 2001 he was Deputy Vice-Principal and Director for Research Development at King's College London, where he remains a Visiting Professor of Defence Studies. The data clearly indicate, however, that the class I and class II components of the major histocompatibility complex are unusually hypermethylated in several T-ALL-derived cell lines, while ATL T-cell lines do not substantially differ in this respect from normal peripheral blood T-cells. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. Replication-defective retroviruses are frequently used as gene carriers for gene transfer into target cells. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). Cai, S., Kalisky, T., Dalerba, P., Clarke, M., Stanford Univ. The height of Michael Clarke is in centimeters- 165 cm in meters- 1.65 m in Feet Inches- 5' 5". Here we report that Usp16, a negative regulator of Bmi1/PRC1 function, modulates the Wnt pathway in mammary epithelia, primary human fibroblasts and MEFs, affecting their expansion and self-renewal potential. This suggested that endogenous Bcl-XL could protect cancer cells from p53-mediated apoptosis. SMAD pathways govern epithelial proliferation, and transforming growth factor beta (TGF-beta and BMP signaling through SMAD members has distinct effects on mammary development and homeostasis. Professor Michael Clarke was Director General of the Royal United Services Institute (RUSI) from 2007 to 2015. In vivo, this colonic cKit(+) population was regulated by Notch signaling; administration of a -secretase inhibitor to mice increased the number of cKit(+) cells. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Amy Smith Berylson Professor of Materials Science and Professor of Chemistry & Chemical Biology. 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. View details for Web of Science ID 000243488100004. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. At the molecular level, Usp16 affects Rspo-mediated phosphorylation of LRP6. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. View details for Web of Science ID 000168968300004. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. In Down's Syndrome (DS), triplication of Usp16 dampens the activation of the Wnt pathway. (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. An interleukin-6 family member, interleukin-11 is identified as a secondary target of twinfilin 1 in the microRNA-30c signalling pathway. This cell line contains a wild-type p53 gene and is an ideal model for studying the mechanism of IR resistance in this disease. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. Yoo, S., Chandhasin, C., Del Rosario, J. R., Chen, Y. K., Stafford, J., Quake, S., Perabo, F., Clarke, M. F. Pharmacologic characterization of TACH101, a first-in-class KDM4 inhibitor for development as a cancer therapeutic. PROF. MICHAEL CLARKE (Director, Royal United Services Institute): I think the United States has been behind us in this respect. View details for Web of Science ID A1992GX27300015. Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. Adjunct Associate Professor Jon Womersley. The wild-type p53/GFP fusion protein was localized in the cytoplasm, the nucleus, or both compartments in a subset of the cells. Down's syndrome results from full or partial trisomy of chromosome 21. Here we developed a CSC model for the study of human colorectal cancer (CRC). These results indicated the involvement of cis-acting sequences in the regulation of p53 subcellular localization. CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRP, on macrophages and other immune cells. Surface markers that displayed intratumor heterogeneous expression among epithelial cancer cells were selected for cell sorting and tumorigenicity experiments. These include the nuclear import and export signals of p53, inhibition of p53 nuclear import and export by oligomerization, MDM2-mediated p53 nuclear export, and possible roles of p53 phosphorylation in regulating p53 cellular localization. When a virus expressing the proapoptotic gene Bc1-xs (Clarke et al., Proc. Hernandez-Alcoceba, R., Pihalja, M., Qian, D. L., Clarke, M. F. Differential gene expression profiling of adult murine hematopoietic stem cells. View details for Web of Science ID A1984SV56900010. 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. Clarke, Clifton - Professor: Business Management Clement, Anthony E. - Associate Professor: Mathematics Cohen, Douglas - Lecturer/Doctoral Scholar: . Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. 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. Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. This problem can be addressed by allowing limited viral replication. 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. The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Fundamentally, the system is the paradigm of a complex interactive tissue, in which the proliferation and regulated differentiation of one parenchymal cell type (the hematopoietic stem cell) is governed by the surrounding stromal cells. Zarour, L. R., Anand, S., Billingsley, K. G., Bisson, W. H., Cercek, A., Clarke, M. F., Coussens, L. M., Gast, C. E., Geltzeiler, C. B., Hansen, L., Kelley, K. A., Lopez, C. D., Rana, S. R., Ruhl, R., Tsikitis, V. L., Vaccaro, G. M., Wong, M. H., Mayo, S. C. Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age. Comparison of IRF3 and NF-B induction in STAT1(-/-) mice revealed that murine but not simian RRV mediated accumulation of IkB- protein and decreased transcription of NF-B-dependent genes. View details for DOI 10.1073/pnas.0530291100, View details for Web of Science ID 000182058400082, View details for PubMedCentralID PMC153034. Some mice were given the RTK inhibitor imatinib after injection of cancer cells; tumor growth was measured based on bioluminescence. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. View details for Web of Science ID A1992JB22100010. View details for DOI 10.1016/j.jviromet.2011.02.015, View details for Web of Science ID 000290836400014, View details for PubMedCentralID PMC3086718, View details for DOI 10.1158/1538-7445.AM2011-1582, View details for Web of Science ID 000209701302286, View details for Web of Science ID 000289796200068. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. View details for DOI 10.1073/pnas.1121623109, View details for DOI 10.1158/1538-7445.AM2012-3331, View details for Web of Science ID 000209701505088, View details for DOI 10.1158/1538-7445.AM2012-1012, View details for Web of Science ID 000209701505194. View details for DOI 10.1073/pnas.0703478104, View details for Web of Science ID 000247363000044, View details for PubMedCentralID PMC1891215. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies. A key event in this process is the deregulation of normal self-renewal in these cells. To better understand the molecular basis of radiation-induced cell death, we studied the role of the bcl-2 oncogene and the p53 tumor suppressor gene in this process. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. [2] [3] Biography [ edit] Josephs, S. F., Ratner, L., Clarke, M. F., Westin, E. H., Reitz, M. S., WONGSTAAL, F. DIFFERENTIAL METHYLATION OF CLASS-I HISTOCOMPATIBILITY ANTIGEN GENES IN T-CELL LINES DERIVED FROM TWO DIFFERENT TYPES OF T-CELL MALIGNANCIES, TRANSFORMATION OF NIH 3T3-CELLS BY A HUMAN C-SIS CDNA CLONE. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Sci. For more information, please contact Ruth Lira, 650-723-1367. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. The tumor suppressor protein p53 has been identified as a key regulator of apoptosis in both normal and malignant hematopoietic cells. This demonstrates that there are distinct genetic determinants of the frequencies of HSCs and restricted progenitors in vivo. To date, therapies targeting end-stage disease plaques, tangles, or inflammation have limited efficacy. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. 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. Danish, R., ELAWAR, O., Weber, B. L., Langmore, J., Turka, L. A., Ryan, J. J., Clarke, M. F. CAN DEXTER CULTURES SUPPORT STEM-CELL PROLIFERATION. Unfortunately, viruses are limited in their ability to diffuse through tissue. He is member of the Board of Parks Victoria. 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. . In breast cancer, while a subset of cells with epithelial and mesenchymal phenotypes have stem cell activity, in many cells that have lost epithelial characteristics with increased expression of mesenchymal genes, have decreased tumor-initiating capacity and plasticity. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. Prior to that he was Professor of Defence Studies at King's College London, and Deputy Vice-Principal for Research Development. View details for Web of Science ID 000186230600042, View details for PubMedCentralID PMC2614897, View details for Web of Science ID 000184162600127. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation. Heights. Synchronized cells allowed to pass out of G1 prior to being placed at 32.5 degrees C continued to cycle until subsequently arrested in G1; loss of viability occurred following G1 arrest. Jasty, R., Lu, J. Y., Irwin, T., Suchard, S., Clarke, M. F., Castle, V. P. Cooperation of a single lysine mutation and a C-terminal domain in the cytoplasmic sequestration of the p53 protein, A method of limited replication for the efficient in vivo delivery of adenovirus to cancer cells. According to this second scenario, tumors act as caricatures of their corresponding normal tissues and are sustained in their growth by a pathological counterpart of normal adult stem cells, cancer stem cells. View details for DOI 10.1196/annals.1349.012, View details for Web of Science ID 000230894100011, View details for Web of Science ID 000225161400025. View details for Web of Science ID A1992KX78000004. 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. View details for Web of Science ID A1984TY56600006. Weber, B. L., Westin, E. H., Clarke, M. F. ALTERNATIVE SPLICING OF THE HUMAN C-MYB GENE. The identification of promoters that are preferentially active in cancer cells is the starting point for this strategy. The Thy-1-CD24medCD49fhigh phenotype contains a rare progenitor population that is able to form primary mammary outgrowths with significantly decreased serial in vivo transplantation potential.CONCLUSIONS: Therefore, Thy-1 expression in the immature cell compartment is a useful tool to study the functional heterogeneity that drives mammary gland development and has implications for disease etiology. View details for Web of Science ID A1996UG75600003. Upon transfer to 32.5 degrees C, these G1 synchronized cell populations quickly lost viability. Taken together, these results strongly suggest that the stromal cell layer does produce important factors for active hematopoiesis during its growth to confluence. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.). One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. Emerson, S. G., Palsson, B. O., Clarke, M. F. INFLUENCE OF MEDIUM EXCHANGE SCHEDULES ON METABOLIC, GROWTH, AND GM-CSF SECRETION RATES OF GENETICALLY ENGINEERED NIH-3T3 CELLS. Such a block presents a problem because radiation and chemotherapy, standard cancer treatments, ultimately exert their effect by induction of apoptosis and would also be made less effective. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. View details for DOI 10.1016/j.patbio.2006.01.004, View details for Web of Science ID 000236287600008. Free UK delivery for orders 30 and over. Using mammary epithelial-specific mouse models targeting Trp53 and Cdkn2a, the gene coding for p16INK4a and p19ARF, we demonstrate that p53, p16INK4a, and p19ARF do not play a significant role in the limitation of normal mammary epithelium self-renewal and proliferation, whereas in the presence of the inflammatory cytokine TNF-, Trp53-/-Cdkn2a-/- mammary basal cells exhibit amplified proliferation. Professor Clarke was presented by Professor Len Scott from the Department of International Politics. Ryan, J. J., Danish, R., Gottlieb, C. A., Clarke, M. F. C-MYB EFFECTS ON KINETIC EVENTS DURING MEL CELL-DIFFERENTIATION. In patients with colorectal cancer (CRC) that metastasizesto the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. View details for Web of Science ID 000345777300014. Park, I., Qian, D., Kiel, M., Becker, M., Prohaska, S., Weissman, I., Morrison, S., Clarke, M. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. 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. Through tissue human colorectal cancer ( CRC ) and restricted progenitors in vivo Rspo-mediated phosphorylation of LRP6 distinguish. In CSCs are associated with increased expression of free radical scavenging systems prof. Clarke! California ; 9 de julio de 1956 ) es un actor y Director de cine estadounidense & amp ; Biology... Of stem cells, or both compartments in a subset of the Wnt.... Both compartments in a subset of the G1 specificity of p53-mediated cell cycle arrest a wild-type p53 and... 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