professor michael clarke biography
Abnormal p53 cellular localization has been considered to be one of the mechanisms that could inactivate p53 function. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. The lactate/glucose and ammonia/glutamine yield coefficients, however, remained invariant at about 1.9 and 1.0 mol/mol, respectively, under all medium perfusion conditions. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. Upon inactivation of KrasG12D , tumors initially regress and enter remission. 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. 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. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. Therefore, we set out to identify a potential earlier targetable phenotype. In recent years solid tumors were studied utilizing similar techniques in mice. KIT knockdown cells had increased expression of enterocyte markers, decreased expression of cycling genes, and, unexpectedly, increased expression of LGR5 associated genes. This development may play an important role in realizing human gene therapy. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Sky's defence analyst Prof Michael Clarke gives his opinion on the critical elements of the war in Ukraine and on what could come next Why you can trust Sky News Watch Next Tuesday's Press Preview PM announces 'major breakthrough' Baroness Betty Boothroyd dies A day of history, a day of reckoning On the frontline in Vuhledar Infection with this vector induced apoptosis in vitro. 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. Limiting dilution transplantations of breast epithelial cells devoid of TLR2 or MYD88 revealed a significant decrease in mammary repopulating unit frequency compared with the control. Expression of wild-type p53 phenotype for 24 hr before FdUrd treatment provided HT29 cells with virtually complete protection from cytotoxicity caused by this drug. In spite of substantial differences in the extent of methylation of class I-related genes, no obvious differences exist among these cell types in their levels of expression of HLA-A and -B antigens. The downstream effectors of TLR2 are expressed by normal intestinal and mammary epithelia, including the stem/progenitor cells. Michael Clarke is a UK academic and "terror expert". 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.'. We show that single-cell RNA-seq can be used to perform accurate quantitative transcriptome measurement in individual cells with a relatively small number of sequencing reads and that sequencing large numbers of single cells can recapitulate bulk transcriptome complexity. Unfortunately, viruses are limited in their ability to diffuse through tissue. 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. View details for PubMedCentralID PMC5698470. The nucleotide sequence of a transforming human c-sis complementary DNA shows an open reading frame 723 base pairs in length located downstream from an in-phase terminator thymine-guanine-adenine codon. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. Adjunct Professor Michael Whitehouse. These results suggest that LEFTY1 is an endogenous dual-SMAD inhibitor and that suppressing its function may represent a therapeutic vulnerability in breast cancer. Adjunct Senior Lecturer Dr Urs Wermuth. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies. As precision medicine increases the response rate of treatment, tumors frequently bypass inhibition and reoccur. View details for Web of Science ID 000268227400008, View details for Web of Science ID 000209702603139, View details for Web of Science ID 000209701800291. 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. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. It has 234 amino acids consisting of a central RGS box and short divergent NH(2) and COOH termini. Recently, various new players that regulate HSC maintenance (e.g. The possible significance of this finding is discussed. 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. In this episode, Eliot Wilson talks to Professor Michael Clarke, former head of the Royal United Services Institute, about the UK's Integrated Review and how far it represents a break from traditional thinking on our place in the world. He is a Professor at La Trobe University in Melbourne, Victoria, where he has worked since 1992. bcl-x is a member of the bcl-2 family of genes and by alternative splicing gives rise to two distinct mRNAs: bcl-xL and bcl-xS. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. The induced p53 is functional as p53-responsive genes (Waf-1 and MDM-2) are appropriately induced following IR. Associate Professor of Instruction; PhD. View details for DOI 10.1634/stemcells.2007-0440, View details for Web of Science ID 000253372600008. Recent evidence suggests that a subset of cancer cells within some tumors, the so-called cancer stem cells, may drive the growth and metastasis of these tumors. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Investigating mechanisms of cancer stern cell radioresistance. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. View details for DOI 10.1016/j.stem.2009.05.019, View details for Web of Science ID 000269511900010. 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. G1 arrest at 37.5 degrees C, utilizing either mimosine or isoleucine deprivation, does not lead to rapid cell death. Transient overexpression of RGS18 attenuated inositol phosphates production via angiotensin receptor and transcriptional activation through cAMP-responsive element via M1 muscarinic receptor. We assessed tumorigenicity using limiting dilution analysis.KIT and KITLG were expressed heterogeneously by a subset of human colon tumors. We find that normal, regenerating, and developing gland maintain a specific branching pattern. The successful ex vivo reconstruction of human bone marrow is an extraordinarily important basic scientific and clinical goal. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Bcl11b(high) cells are enriched for cells that can regenerate mammary glands in secondary transplants. INGRAHAM, L. M., Weening, R. S., Clarke, M. F., Boxer, L. A., Baehner, R. L. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Directed Reading in Stem Cell Biology and Regenerative Medicine, Stem Cell Biology and Regenerative Medicine (Phd Program), DOI 10.1146/annurev.cellbio.22.010305.104154. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression. Adjunct Senior Lecturer Dr Jan Warnken. 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. Mini Bio (1) Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. Prior to coming to UK, Dr. Clark was the Chief Economist for the Kentucky Legislative Research . Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P. S., Rothenberg, M. E., Leyrat, A. Sequences within this region were identical to those previously determined for the exons of the normal human c-sis gene. View details for Web of Science ID A1991FC72500007. This suggests that expression of DR antigens also can be modulated post-transcriptionally. Therefore, senescence of stem cells must be prevented. Programmed cell death, or apoptosis, may play an important role in the regulation of hematopoiesis. An additional explanation, however, envisages human tumors not as mere monoclonal expansions of transformed cells, but rather as complex tridimensional tissues where cancer cells become functionally heterogeneous as a result of differentiation. Adjunct Associate Professor Jon Womersley. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). View details for Web of Science ID 000073794800011. A temperature-sensitive mutant of murine p53 (p53Val-135) and/or bcl-2 was transfected into murine erythroleukemia cells (MEL, DP16-1, which are null in p53). View details for Web of Science ID 000243488100004. The reasons for the limited longevity are unknown. His writingson justice, ethics, democracy, and markets--have been translated into 27 languages. 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. in Management and an M.S. This has been recently shown in an in vivo model, where overexpression of Bcl-XL, is a crucial step in the progression from hyperplasia to neoplasia and is accompanied by a significant decrease in tumor apoptosis [56]. 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. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In 2007, he became the Director of the Royal United Services Institute. View details for Web of Science ID 000171898900054. Ealovega, M. W., McGinnis, P. K., Sumantran, V. N., Clarke, M. F., Wicha, M. S. A RECOMBINANT BCL-X(S) ADENOVIRUS SELECTIVELY INDUCES APOPTOSIS IN CANCER-CELLS BUT NOT IN NORMAL BONE-MARROW CELLS. Zhao, C., Cai, S., Shin, K., Lim, A., Kalisky, T., Lu, W., Clarke, M. F., Beachy, P. A. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures. Cancer stem cells and tumor metastasis: First steps into uncharted territory, Bmi-1-green fluorescent protein-knock-in mice reveal the dynamic regulation of Bmi-1 expression in normal and leukemic hematopoietic cells. View details for Web of Science ID 000243301800039. Treatment-related mortality was 10%. View details for Web of Science ID 000079323200036. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. View details for DOI 10.1016/j.semradonc.2008.11.002, View details for Web of Science ID 000264310800003, View details for PubMedCentralID PMC2789266. Tumors originated from EpCAM(high)/CD44+ cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy. Hernandez-Alcoceba, R., Pihalja, M., Qian, D. L., Clarke, M. F. Differential gene expression profiling of adult murine hematopoietic stem cells. Bcl-2 prevented radiation-induced cell death in DP16-1 cells expressing wtp53 and delayed radiation-induced cell death in DP16-1 cells without wtp53. Most cancers comprise a heterogenous population of cells with marked differences in their proliferative potential as well as the ability to reconstitute the tumor upon transplantation. Although the existence of mammary stem cells has been suggested by serial transplantation studies in mice, their identification has been hindered by the lack of specific surface markers, and by the absence of suitable in vitro assays for testing stem cell properties: self-renewal and ability to generate differentiated progeny. View details for DOI 10.1073/pnas.0900089106, View details for Web of Science ID 000270573602118, View details for DOI 10.1007/978-1-60327-087-8_38, View details for Web of Science ID 000267947100039, View details for Web of Science ID 000311099200058. These findings demonstrate that p53 overexpression renders Shep-1 cells IR-sensitive and suggest that large quantities of exogenous p53 can overcome the factors inhibiting p53-mediated, IR-induced apoptosis. High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA-protein interactions. Three seminoma patients remain progression-free. The results demonstrate that cell sorting is effective, much faster and less likely to alter tumor cell phenotype than traditional methods for removing LDV from xenograft models. Inhibition of TLR2, its co-receptor CD14, or its downstream targets MYD88 and IRAK1 inhibits growth of human breast cancers in vitro and in vivo. 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). Cooh termini the induced p53 is functional as p53-responsive genes ( Waf-1 and MDM-2 ) are appropriately induced IR. Were expressed heterogeneously by a subset of human bone marrow is an endogenous dual-SMAD inhibitor and that its! 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