professor michael clarke biography

Profiles. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects. The hair color is Light brown and the eye color is Blue. Tumors injected four times with the bcl-xs adenovirus showed a 50% reduction in size. Using model cell lines (NIH-3T3 and CV-1), it was shown that gene transfer rates can be increased by more than an order of magnitude using the same concentration infection medium. 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. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. 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. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. It contains three regions: a KpnI repeat, a unique cellular region (UCR), and the U3 + R sequence of the human T-lymphotropic virus type I LTR. Adjunct Associate Professor Dianne Watters. 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. View details for Web of Science ID A1995RP92400014. van Weele, L. J., Scheeren, F. A., Cai, S. n., Kuo, A. H., Qian, D. n., Ho, W. H., Clarke, M. F. Single-cell transcriptional diversity is a hallmark of developmental potential. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. [1] Clarke is a former Deputy Vice-Principal and Director of Research Development at King's College London, where he remains a Visiting Professor of Defence Studies. 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. 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. In the other clone, incorporation of a new exon leads to introduction of a translation stop codon leading to loss of the entire carboxy terminus of the protein. - Associate Professor: Business Management Indomethacin (4 x 10(-4) M) and ETYA (2 x 10(-5) M) did inhibit oxygen utilization and superoxide production. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. 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. Email: charlotte.clarke@ed.ac.uk. Rapid medium exchanged LTHBMCs were established on surfaces precoated with human natural fibronectin and type 1 rat tail collagen. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. These data are consistent with the idea that the human T-lymphotropic virus type I LTR contains an enhancer which can activate upstream sequences in cis. Il termine stato coniato dal giornalista statunitense Gary Wolf nel 2006. The pattern of triple mutant multipotent progenitor response to growth factors resembles that of wild-type multipotent progenitors but not wild-type HSCs. Dr. Michael F. Clarke is the Karel and Avice Beekhuis Professor in Cancer Biology and Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. Parks, I. K., Klug, C. A., Li, K. J., Jerabek, L., Li, L. H., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., Clarke, M. F. A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors. James H. Clarke, Michael P. Vandenbergh . To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. 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. The Shep-1 neuroblastoma cell line is highly resistant to IR. Lee, J. J., Rothenberg, M. E., Seeley, E. S., Zimdahl, B., Kawano, S., Lu, W., Shin, K., Sakata-Kato, T., Chen, J. K., Diehn, M., Clarke, M. F., Beachy, P. A. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. Some factors that regulate this process of self-renewal are conserved from fruit fly to humans. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. 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). KIT knockdown cells had increased expression of enterocyte markers, decreased expression of cycling genes, and, unexpectedly, increased expression of LGR5 associated genes. View details for DOI 10.1016/j.stem.2013.06.012. 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. Al-Hajj, M., Becker, M. W., Wichal, M., Weissman, I., Clarke, M. F. Bmi1, stem cells, and senescence regulation. Science-Fiction, auch Sciencefiction geschrieben ([sans fkn]; englisch science: Naturwissenschaft, fiction: Fiktion), ist ein Genre in Literatur (Prosa, Comic), Film, Hrspiel, Videospiel und Kunst.Charakteristisch sind wissenschaftlich-technische Spekulationen, Raumfahrtthemen, ferne Zukunft, fremde Zivilisationen und meist zuknftige Entwicklungen. The C57BL/Ka-Thy-1.1 alleles were partially dominant. Using these targeted reporter mice, we demonstrated that Bmi-1 is expressed in hematopoietic stem cells (HSCs) at its highest levels and downregulated upon commitment to differentiation. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells that has the exclusive ability to extensively proliferate and form new tumors can be identified based on marker expression. To direct the replication of the virus to breast cancer, we have considered one characteristic present in a great proportion of these cancers, which is the expression of estrogen receptors (ERs). We will discuss the important implications of this mammary tumour stem-cell model. Cytoplasmic sequestration of the mt p53 was dependent upon the C-terminal region (residues 326-355) of the protein. View details for Web of Science ID A1991GR93700016. Biography. Thus a limiting serum component is responsible for the altered metabolic and growth rates. While cell lines expressing p53 alone rapidly died, those cells co-expressing Bcl-XL survived. Lys-305 is needed for nuclear import of p53 protein, and amino acid residues 326-355 can sequester mt p53 in the cytoplasm. Genetic upregulation of the Wnt pathway in Ts65Dn mice rescues the proliferation defect observed in mammary epithelial cells. Despite this central role, the mechanism of action of Bcl-2 is not yet clear. Li, C., Heidt, D. G., Dalerba, P., Burant, C. F., Zhang, L., Adsay, V., Wicha, M., Clarke, M. F., Simeone, D. M. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. KrasG12D -independent tumor cells show a strong mesenchymal profile with active RAS-RAF-MEK-ERK (MAPK/ERK) signaling. Deletion of MYD88 or TLR2 in the intestinal epithelium markedly reduces DSS-induced colitis regeneration and spontaneous tumour development in mice. 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. His laboratory is pursuing the identification of cancer stem cells in other tumors so that they can be studied. We find that normal, regenerating, and developing gland maintain a specific branching pattern. Dr Ofer Fridman spoke on CNN about the nature of Russian hybrid warfare, discussed Israel's position in Russia and Ukraine border tensions in The Jerusalem Post and was in The i on whether Russia would attack the UK over the imposed sanctions. This problem can be addressed by allowing limited viral replication. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory . The traditional approaches to remove LDV from tumor cells, by transplanting tumors into rats or culturing tumor cells in vitro, are inefficient, labor-intensive and time-consuming. 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. View details for Web of Science ID A1990DY35100036. President Biden has reaffirmed the U.S. commitment to the North Atlantic Treaty Organization (NATO) and collective defense and has stated that a strong European Union is in the U.S. interest. 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. 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. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. These studies show that the metabolic and secretory behavior of genetically engineered cells is influenced by the medium exchange schedule. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. Hoey, T., Yen, W., Axelrod, F., Basi, J., Donigian, L., Dylla, S., Fitch-Bruhns, M., Lazetic, S., Park, I., Sato, A., Satyal, S., Wang, X., Clarke, M. F., Lewicki, J., Gurney, A. View details for Web of Science ID 000072317400002. LEFTY1 binds BMPR2 to suppress BMP7-induced activation of SMAD5, and this LEFTY1-BMPR2 interaction is specific to tumor-initiating cells in triple-negative breast cancer xenografts that rely on LEFTY1 for growth. A full-length human c-myb cDNA clone has been isolated from a CCRF-CEM leukemia cell cDNA library. The blocking effect of the CSD is not due to the enhancement of nuclear export or oligomerization of the p53. He has published internationally on the ecology and conservation biology of birds, reptiles, mammals, fish and plants. Differences in self-renewal pathways between normal and malignant stem cells could be targeted by new therapeutic agents to eliminate cancer stem cells. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. View details for Web of Science ID A1984SP90200011. To characterize further the function of these two domains, we demonstrate in this report that the previously described major nuclear localization signal works together with Lys(305)-Arg(306) to form a bipartite and functional nuclear localization sequence (NLS) for p53 nuclear import. A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. This decrease in survival began 48 h following radiation. Reinitz, F., Chen, E. Y., Nicolis di Robilant, B., Chuluun, B., Antony, J., Jones, R. C., Gubbi, N., Lee, K., Ho, W. H., Kolluru, S. S., Qian, D., Adorno, M., Piltti, K., Anderson, A., Monje, M., Heller, H. C., Quake, S. R., Clarke, M. F. LEFTY1 Is a Dual-SMAD Inhibitor that Promotes Mammary Progenitor Growth and Tumorigenesis. 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. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. Dylla, S. J., Beviglia, L., Park, I., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., Clarke, M. F., Hoey, T., Lewicki, J., Gurney, A. L. Characterizing metastatic cancer stem cells from human breast cancer. 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. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. Control experiments show that positioning is not due to the 21-bp repeats or to end effects. Metastasis remains a significant challenge in treating cancer. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. 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 complexity and inefficiency of chromatin immunoprecipitation strategies restrict their sensitivity and application when examining rare cell populations. 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. Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Programmed cell death (PCD) plays an important role in normal and malignant hematopoieis. Here, we report the results of using a bioreactor system to expand hematopoietic cells after a brief retrovirus infection using a high titer, replication defective virus encoding for murine CD18. However, KITLG-knockdown DLD1 cells formed smaller xenograft tumors than control cells. Han, J. S., Nunez, G., Wicha, M. S., Clarke, M. F. Prevention of fluorodeoxyuridine-induced cytotoxicity and DNA damage in HT29 colon carcinoma cells by conditional expression of wild-type p53 phenotype. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. Wu, A. R., Hiatt, J. A shift-up in medium perfusion rates from 3.5/week to 7/week resulted in increased metabolic rates that resembled those observed in the cultures that were exchanged at the 7/week rate throughout, showing that the metabolic rates could be directly controlled by the perfusion rate. 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. Thus, we reveal USP16 as a novel target in an AD model that can both ameliorate the NPC defect and rescue memory and learning through its regulation of both Cdkn2a and BMP signaling.'. In normal mouse epithelium, LEFTY1 expression in a subset of luminal cells and rare basal cells opposes BMP7 to promote ductal branching. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Solid tumors arise in organs that contain stem cell populations. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details for PubMedCentralID PMC2731699. We have developed an in vitro cultivation system that allows for propagation of human mammary epithelial cells (HMECs) in an undifferentiated state, based on their ability to proliferate in suspension, as nonadherent mammospheres. At the molecular level, Usp16 affects Rspo-mediated phosphorylation of LRP6. 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 previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. 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. Cancer cells with endogenous KIT expression were more tumorigenic in mice.KIT and KITLG are expressed by a subset of human colon tumors. 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. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. 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. He also carries out research into the cellular responses to anti-cancer drugs. 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. 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. The molecular mechanisms that limit the proliferation capacity of multipotent progenitors and other more mature progenitors are not fully understood. We also discuss thelatest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. 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Ses ) associated with CD47 in certain cancer cell types factors that regulate this process self-renewal... View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details DOI... The p53 epithelial-to-mesenchymal transition has been isolated from a CCRF-CEM leukemia cell cDNA library behavior of genetically cells. Needed for nuclear import of p53 protein, and amino acid residues 326-355 ) of the Wnt pathway in mice..., but the functional link and signalling pathways remain to be elucidated reduction in.. Y director de cine estadounidense, Medicine & amp ; Environmental Biot Galway... Growth rates on surfaces precoated with human natural fibronectin and type 1 rat collagen! Ras-Raf-Mek-Erk ( MAPK/ERK ) signaling, but the functional link and signalling pathways remain to be elucidated multipotent response. Lines expressing p53 alone rapidly died, those cells co-expressing Bcl-XL survived cells co-expressing Bcl-XL survived,. 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