professor michael clarke biographyprofessor michael clarke biography

professor michael clarke biography professor michael clarke biography

Professor of Health in Social Science; College Dean International; EFI Director of Global Communities. These findings have important implications for the development and evaluation of oncologic therapies and present opportunities for potential gains in patient outcome. Sumantran, V. N., Ealovega, M. W., Nunez, G., Clarke, M. F., Wicha, M. S. In vitro expansion of hematopoietic cells for clinical application. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. 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. Because these observations conflict with previously suggested models for FdUrd-induced damage to parental DNA, we propose an alternative model to explain how incorporation of uracil into nascent DNA might result in single-strand breaks in the opposite (parental) strand and how these breaks might be converted to the double-strand breaks that produce cell death. Isobe, T., Zarnegar, M. A., Abdel-Wahab, O., Clarke, M. F. A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. Here, using molecular clones of HTLV and human major histocompatibility antigen DNA, we have shown homology between the envelope gene region of HTLV and the region of an HLA-B locus gene which codes for the extracellular portion of a class I histocompatibility antigen. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells. To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Adjunct Associate Professor David Welsh. F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. View details for PubMedCentralID PMC3816928. C-myb, the normal cellular homolog of the retroviral transforming gene v-myb, encodes a nuclear, transcriptional regulatory protein (p75c-myb). George Malcolm (1917-1997), Pianist, Cembalist, Dirigent und Komponist. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. Human tumors where evidence of cancer stem cells has been published include tumors of the breast, brain, pancreas, head and neck, and colon. In DNA from the T-cells not expressing DR alpha mRNA, all of the potential HpaII sites within the BglII fragment appeared to be methylated. Zabala, M., Lobo, N. A., Seoane, J. [2] [3] Biography [ edit] Mann, D. L., Clark, J., Clarke, M., Reitz, M., Popovic, M., Franchini, G., Trainor, C. D., STRONG, D. M., Blattner, W. A., Gallo, R. C. Presence of HTLV in a subset of T cells from an infected patient: some immunochemical properties of the infected cells. Taken together, these results show that c-myb acts very late in the process of differentiation. Filter By. View details for DOI 10.1056/NEJMc1602584, View details for PubMedCentralID PMC4955394. In normal mouse epithelium, LEFTY1 expression in a subset of luminal cells and rare basal cells opposes BMP7 to promote ductal branching. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT. 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. View details for Web of Science ID A1990DY35100036. View details for Web of Science ID 000166430900009. CHUCK, A. S., Clarke, M. F., Palsson, B. O. bcl-x(s) gene therapy induces apoptosis of human mammary tumors in nude mice. Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Gulati, G. S., Sikandar, S. S., Wesche, D. J., Manjunath, A. n., Bharadwaj, A. n., Berger, M. J., Ilagan, F. n., Kuo, A. H., Hsieh, R. W., Cai, S. n., Zabala, M. n., Scheeren, F. A., Lobo, N. A., Qian, D. n., Yu, F. B., Dirbas, F. M., Clarke, M. F., Newman, A. M. Ageing hallmarks exhibit organ-specific temporal signatures. View details for Web of Science ID A1995RY96700021. 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. 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. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: (1) single cells and (2) multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Professor Field: Brazil, Latin America, Historical Geography, Environmental History Contact Information Email SBELL@GEOG.UCLA.EDU Office 1255 Bunche Hall Phone Scot Brown Associate Professor Field: United States Contact Information Email SBROWN@HISTORY.UCLA.EDU Office 1321 Rolfe Phone 310-825-5502 Eddie R. Cole Associate Professor The p53-dependent pathway results in cell death via apoptosis and occurs approximately 24 h following radiation. View details for Web of Science ID A1991FC72500007. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. Zarnegar, M. A., Reinitz, F. n., Newman, A. M., Clarke, M. F. CDX2 as a Prognostic Biomarker in Colon Cancer. Here we describe c-myb-transformed MEL clones which undergo delayed expression of the exogenous c-myb following 3-5 days of culture in DMSO. High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. Comparing ChIP results for two modified histone protein targets, we showed our automated microfluidic ChIP (AutoChIP) from 2,000 cells to be comparable to that of conventional ChIP methods using 50,000-500,000 cells. Taken together, these results suggest that Bcl11b acts as acentral intrinsic regulator of mammary epithelial stem cell quiescence and exhaustion and is necessary for long-term maintenance of the mammary gland. Tel: +44 (0)131 650 4327. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs. Kim et al. 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. 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. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. This is an overview of the elements and molecules involved in p53 nucleocytoplasmic transportation. He is the Karel and Avice Beekhuis Professor in Cancer Biology and Associate Director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Michael Clarke (academic) is a British academic who specialises in defence studies. The Bcl-2 family of proteins: regulators of cell death and survival. This concept was first demonstrated in the study of leukemia where only cells with specific surface antigen profiles were able to cause leukemia when engrafted into immunodeficient mice. View details for DOI 10.1158/0008-5472.CAN-06-2030, View details for Web of Science ID 000244137300026. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral nervous systems. 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. We find that normal, regenerating, and developing gland maintain a specific branching pattern. Weber, B. L., Westin, E. H., Clarke, M. F. ALTERNATIVE SPLICING OF THE HUMAN C-MYB GENE. In culture, codelivery of virus and pE1 resulted in a large increase in infected cells when compared with control cells exposed to virus and pUC19. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. We have previously shown that two human T-cell lines (HSB and 8402) derived from patients with childhood T-cell ALL (T-ALL) do not synthesize detectable mRNA for HLA-DR alpha. Control cultures that were exposed to conCM after 4 weeks in culture significantly improved their cell productivity during the latter 4 weeks of culture compared with control. To achieve long-lasting responses in the clinic to RAS-fueled cancer, treatment will need to focus in parallel on obstructing tumors from adapting to oncogene inhibition. Patients with KIT-expressing colon tumors can benefit from KIT RTK inhibitors. Sci. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases. Despite intensive study of p53, the regulation of p53 cellular localization is still poorly understood. Prior to that he was Professor of Defence Studies at King's College London, and Deputy Vice-Principal for Research Development. Bcl-XS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. Finally, questions regarding p53 cellular trafficking will also be discussed. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). "Bulk" measurements of antiviral innate immune responses from pooled cells yield averaged signals and do not reveal underlying signaling heterogeneity in infected and bystander single cells. A., Chen, L., Levy, R. Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. 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. Clinical and Therapeutic Implications of Cancer Stem Cells Reply, Solid tumor cancer stem cells: From bench to bedside, ASXL1 regulates cellular differentiation and initiates tumorigenesis in colon. 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. A key event in this process is the deregulation of normal self-renewal in these cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Professor Michael Clarke was Director-General of the Royal United Services Institute (RUSI) from 2007 to 2015 when he retired from that role. 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. Although the colon also contains Lgr5(+) stem cells, it does not contain Paneth cells. Investigating mechanisms of cancer stern cell radioresistance. Growing up on Chicago's South Side in the 1960s and 1970s, Michael Clarke Duncan experienced poverty and crime as an unfortunately normal part of life. Prof Mike Clarke is Professor of Zoology at La Trobe University. Professor Clarke is a former Deputy Vice . Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. 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. Ailles, L., Prince, M., Joshua, B., Doweck, I., Kaplan, M., Clarke, M., Weissman, I. 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. 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. Ageing is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. 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. Our multidisciplinary group held a state-of-the-science symposium this past year to review advancesin this rapidly evolving field. 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. In addition to his clinical duties in the division of Oncology, Dr . Understanding the pathways that regulate proliferation, self-renewal, survival, and differentiation of malignant and normal stem cells may shed light on mechanisms that lead to cancer and suggest better modes of treatment. Intriguingly, overexpression of p53 could reverse the inherent IR resistance of Shep-1 cells. View details for Web of Science ID A1995RP92400014. Hernandez-Alcoceba, R., Pihalja, M., Wicha, M. S., Clarke, M. F. A bipartite nuclear localization signal is required for p53 nuclear import regulated by a carboxyl-terminal domain, Germ cell tumor: Differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling. 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. Michael Clarke 30.99 Hardback Inspiring Impressionism: Michael Clarke 24.95 Paperback Add to Basket The Xinjiang Emergency: Michael Clarke 20.00 Paperback Add to Basket Understanding Foreign Policy: Michael Clarke 28.95 Paperback Add to Basket The Story of Troy (Hardback) Michael Clarke 42.90 Hardback Add to Basket 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. The Bcl-2 protein inhibits apoptosis induced by a variety of signals, in a range of cell types and in diverse organisms, and it is implicated in both normal development and oncogenesis. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2(+) breast cancer. He also carries out research into the cellular responses to anti-cancer drugs. It has been reported that Lysine-305 is needed for the nuclear import of the p53 protein (Liang et al., 1998). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. Using this system, we have generated AdEHT2 and AdEHE2F, two conditionally replicative adenoviruses for the treatment of breast cancer. Fifteen (52%) received both transplants. Recent studies have begun to elucidate the mechanisms controlling hematopoietic stem cell (HSC) self-renewal. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Lobo, N. A., Zabala, M., Qian, D., Clarke, M. F. Serially transplantable mammary epithelial cells express the Thy-1 antigen. 2010). View details for Web of Science ID A1996VX88000036, View details for Web of Science ID A1996VT98300744. View details for DOI 10.1016/j.gde.2008.01.017, View details for Web of Science ID 000256954100008, View details for Web of Science ID 000253701800002, View details for Web of Science ID 000258805300065, View details for Web of Science ID 000251969000893. Wild-type p53 plays a crucial role in the control of apoptosis following ionizing radiation (IR); conversely, mutant p53 is associated with IR resistance. These pathways are commonly repressed in cancer, suggesting a mechanism by which early progenitor cells could gain the ability to self-renew and become malignant with further oncogenic mutations. Multiple cell lines expressing variable levels of exogenous temperature-sensitive p53 were generated. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. These results suggest that radiation-induced cell death occurs by both p53-dependent and p53-independent pathways. Adorno, M., Sikandar, S., Mitra, S. S., Kuo, A., Nicolis Di Robilant, B., Haro-Acosta, V., Ouadah, Y., Quarta, M., Rodriguez, J., Qian, D., Reddy, V. M., Cheshier, S., Garner, C. C., Clarke, M. F. Identification of a cKit(+) Colonic Crypt Base Secretory Cell That Supports Lgr5(+) Stem Cells in Mice. Imatinib inhibited growth of KIT(+) colon cancer organoids in culture and growth of xenograft tumors in mice. In order to better understand HSC self-renewal, we need to understand how these pathways are coordinated. Adjunct Associate Professor Jon Womersley. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues. View details for Web of Science ID A1984SV56900010. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. Email: charlotte.clarke@ed.ac.uk. 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. View details for Web of Science ID A1984SP90200011. A., Clarke, M. F., Quake, S. R. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. 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). 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. Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate colitis and restrain initiation and progression of colitis-induced adenocarcinoma. The downstream effectors of TLR2 are expressed by normal intestinal and mammary epithelia, including the stem/progenitor cells. Parsels, L. A., Zellars, R. C., Loney, T. L., Parsels, J. D., Clarke, M. F., MERCHANT, A. K., Lawrence, T. S., Maybaum, J. Bcl-x(s) enhances adenoviral vector-induced apoptosis in neuroblastoma cells. KrasG12D -independent tumor cells show a strong mesenchymal profile with active RAS-RAF-MEK-ERK (MAPK/ERK) signaling. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. Differences in self-renewal pathways between normal and malignant stem cells could be targeted by new therapeutic agents to eliminate cancer stem cells. Since cancers arise as a result of a series of genetic mutations, a better understanding of the consequences of these mutations on the underlying biology of the neoplastic cells will help the development of more effective therapies. Some mice were given the RTK inhibitor imatinib after injection of cancer cells; tumor growth was measured based on bioluminescence. Here, we show that LEFTY1, a secreted inhibitor of NODAL/SMAD2 signaling, is produced by mammary progenitor cells and, concomitantly, suppresses SMAD2 and SMAD5 signaling to promote long-term proliferation of normal and malignant mammary epithelial cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. When purified from Matrigel contaminated LDV(+) tumors, sorted human breast tumor cells, as well as tumors grown from sorted cells, were shown to be LDV-free, as tested by PCR. Because of the unusual findings of apparently inappropriate HLA antigens in HTLV infected cells, we had previously looked for rearrangement of class I-related genes in HTLV infected cells but failed to find any. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Office Hours: Tuesday 12:00-1:00PM; Thursday 2:00-3:00PM; Friday 10:30-11:30AM. Division of Oncology, Dr containing professor michael clarke biography single 72-bp element forms a positioned core particle a minor of! 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