professor michael clarke biographyprofessor michael clarke biography

It has been viewed by tens of millions of people around the world, including in China, where Sandel was named the "most . Bcl-xs is a dominant negative repressor of Bcl-2 and Bcl-xL, both of which inhibit apoptosis. 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. Here, we demonstrate a simple, yet robust, determinant of developmental potential-the number of expressed genes per cell-and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. ALTERATION OF P53 CONFORMATION AND INDUCTION OF APOPTOSIS IN A MURINE ERYTHROLEUKEMIA CELL-LINE BY DIMETHYLSULFOXIDE, C-MYC AND BCL-2 MODULATE P53 FUNCTION BY ALTERING P53 SUBCELLULAR TRAFFICKING DURING THE CELL-CYCLE. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. 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. The calculated molecular weight of RGS18 is 27,610 and the isoelectric point is 8.63. View details for Web of Science ID 000182941000008. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. Recent studies have uncovered a number of Bcl-2-related gene products that regulate apoptosis either negatively or positively, and Bcl-2 forms heterodimers with at least one of these proteins, Bax. Michael Clarke (academic) is a British academic who specialises in defence studies. Patients generally die of cancer after the failure of current therapies to eliminate residual disease. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). Bystander cells did not display enhanced type I IFN transcription but had elevated levels of certain IFN-stimulated genes, presumably in response to exogenous IFNs secreted from immune cells. Schott, A. F., Apel, I. J., Nunez, G., Clarke, M. F. BCL-2 PROTECTS MURINE ERYTHROLEUKEMIA-CELLS FROM P53-DEPENDENT AND -INDEPENDENT RADIATION-INDUCED CELL-DEATH. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. Herein, we present a discussion around the issues facing treatment of patients with CRCliver metastases, including the relationship of discretegene signatures with prognosis. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. 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. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. 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. 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 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. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. In this study we describe the effect on murine erythroleukemia cells, transfected with a temperature-sensitive mutant p53, of exposure to the differentiating agent dimethylsulfoxide (DMSO). PHD Student in Computer Science. RRV replication was significantly rescued in IFN types I and II, as well as STAT1 (IFN types I, II, and III) deficient mice in contrast to EW, which was only modestly sensitive to IFNs I and II. New treatment modalities are needed for the latter group. Kalani, M. A., Dalerba, P., Clarke, M. F., Leong, S. P. Rothenberg, M., Clarke, M. F., Lanza, R., Gearhart, J., Hogan, B., Melton, D., Pedersen, R., Thomas, E. D., Thomson, J., Wilmut, Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Majetl, R., Becker, M. W., Tian, Q., Lee, T. M., Yan, X., Liu, R., Chiang, J., Hood, L., Clarke, M. F., Weissman, I. L. Identification of Conserved Gene Expression Programs in Epithelial Cancer Stem Cells. A., Beachy, P. A., Berdnik, D., Bilen, B., Brownfield, D., Cain, C., Chan, C. K., Chen, M. B., Clarke, M. F., Conley, S. D., Demers, A., Demir, K., de Morree, A., Divita, T., du Bois, H., Ebadi, H., Espinoza, F. H., Fish, M., Gan, Q., George, B. M., Gillich, A., Gomez-Sjoberg, R., Green, F., Genetiano, G., Gu, X., Gulati, G. S., Hahn, O., Haney, M. S., Hang, Y., Harris, L., He, M., Hosseinzadeh, S., Huang, A., Huang, K. C., Iram, T., Isobe, T., Ives, F., Jones, R. C., Kao, K. S., Karnam, G., Kershner, A. M., Khoury, N., Kim, S. K., Kiss, B. M., Kong, W., Krasnow, M. A., Kumar, M. E., Kuo, C. S., Lam, J., Lee, D. P., Lee, S. E., Lehallier, B., Leventhal, O., Li, G., Li, Q., Liu, L., Lo, A., Lu, W., Lugo-Fagundo, M. F., Manjunath, A., May, A. P., Maynard, A., McKay, M., McNerney, M. W., Merrill, B., Metzger, R. J., Mignardi, M., Min, D., Nabhan, A. N., Ng, K. M., Nguyen, P. K., Noh, J., Nusse, R., Patkar, R., Peng, W. C., Penland, L., Pollard, K., Puccinelli, R., Qi, Z., Rando, T. A., Rulifson, E. J., Segal, J. M., Sikandar, S. S., Sinha, R., Sit, R. V., Sonnenburg, J., Staehli, D., Szade, K., Tan, M., Tato, C., Tellez, K., Torrez Dulgeroff, L. B., Travaglini, K. J., Tropini, C., Tsui, M., Waldburger, L., Wang, B. M., van Weele, L. J., Weinberg, K., Weissman, I. L., Wosczyna, M. N., Wu, S. M., Xiang, J., Xue, S., Yamauchi, K. A., Yang, A. C., Yerra, L. P., Youngyunpipatkul, J., Yu, B., Zanini, F., Zardeneta, M. E., Zee, A., Zhao, C., Zhang, F., Zhang, H., Zhang, M. J., Zhou, L., Zou, J. Automated microfluidic chromatin immunoprecipitation from 2,000 cells. However, to date, genetic modification of the human hematopoietic stem cell has been relatively inefficient. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. The fragment with a tandem repeat of the 72-bp element also does not associate randomly with histones. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. Following high-dose IR, cell fractionation demonstrated that p53 is induced and targeted to the nucleus. In contrast to our previous experience, where all such lines expressed T cell markers, these two cell lines expressed B cell antigens and Ig light chains (kappa on CF-2, lambda on HS). 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. We used immunostaining and fluorescence-activated cell sorting analyses with in vivo administration of a Notch inhibitor and in vitro organoid cultures to characterize different cell types.Multicolor fluorescence-activated cell sorting could isolate distinct regions of colonic crypts. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. Down's syndrome results from full or partial trisomy of chromosome 21. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. Taken together, these results indicate that wild-type p53 induces cell death in murine erythroleukemia cells and that this effect occurs predominantly in the G1 phase of actively cycling cells. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. Professor William Clarke. (2002) demonstrate that the CED-1 homolog, Slug, is a key regulator of apoptosis in the response of early hematopoietic progenitors to gamma radiation. His writingson justice, ethics, democracy, and markets--have been translated into 27 languages. 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. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. Recently, it has become apparent that some oncogenes and tumor suppressor genes also regulate self-renewal, the process by which stem cells maintain themselves. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). All of the DR alpha DNA sequences detected by a cloned DR alpha cDNA probe are contained in a BglII fragment which varies slightly in size (4.0 to 4.8 kilobases) from one individual to another. 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. Disclosure of potential conflicts of interest is found at the end of this article. 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. Multiple cell lines expressing variable levels of exogenous temperature-sensitive p53 were generated. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. Interestingly, exposure to DMSO leads to an alteration of the protein conformation of the p53 mutant to one recognized by a wild-type specific monoclonal antibody. Two clones which initially expressed low levels of human c-myb transcripts and which differentiated normally were subsequently inhibited in their ability to differentiate when grown in successively higher concentrations of methotrexate, due to amplification and enhanced expression of plasmid sequences. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. Just months into the Biden-Harris administration, the change in tone, message, and approach to transatlantic relations is palpable. In Down's Syndrome (DS), triplication of Usp16 dampens the activation of the Wnt pathway. View details for Web of Science ID A1984SY22400007. In contrast to wild-type MEL cells, both clones failed to display phenotypic markers of differentiation and continued to proliferate for up to 10 days of culture. He is a board certified oncologist with extensive training in molecular biology and stem cell biology. The inhibitory effect on F-MEL differentiation appeared to be independent of the early decline in c-myc transcripts which were normally regulated in all cases examined. The human RGS18 ortholog has a tissue-specific expression pattern similar to that of mouse RGS18. In this report we explore the role of Bcl-XL overexpression in protecting cancer cells from p53-mediated apoptosis. On the basis of the wild-type adenovirus type 5, we have constructed a conditionally replicative adenovirus (Ad5ERE2) in which the E1a and E4 promoters have been replaced by a portion of the pS2 promoter containing two estrogen-responsive elements (EREs). 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. A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. The N-bGM-CSFs demonstrated GM-CSF receptor specific binding that was displaceable by excess underivatized protein, with the detected fluorescence signal decreasing with increasing biotin to protein molar ratio. Clarke, M. F., Dick, J. E., Dirks, P. B., Eaves, C. J., Jamieson, C. H., Jones, D. L., Visvader, J., Weissman, I. L., Wahl, G. M. A self-renewal assay for cancer stem cells. 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. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. To study p53 trafficking, the jellyfish green fluorescent protein (GFP) was fused to the wild-type or mutated p53 proteins for fast and sensitive analysis of protein localization in human MCF-7 breast cancer, RKO colon cancer, and SAOS-2 sarcoma cells. Prior to coming to UK, Dr. Clark was the Chief Economist for the Kentucky Legislative Research . 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. All three analogues retained full agonist activity relative to the native protein (EC50 = 10-15 pM) when assayed for the stimulation of human bone marrow progenitor cell growth. Therefore, functional inhibition of Bcl-2 family members is lethal to many cancer cells. View details for Web of Science ID 000186230600042, View details for PubMedCentralID PMC2614897, View details for Web of Science ID 000184162600127. Disease status (no. We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. 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. MACARTHUR, L. H., Clarke, M. F., Westin, E. H. THE INFLUENCE OF EXTRACELLULAR-MATRIX AND STROMA REMODELING ON THE PRODUCTIVITY OF LONG-TERM HUMAN BONE-MARROW CULTURES. These data indicate that the simultaneous regulation of E1A and E4 viral transcription units by the appropriate combination of promoters can increase the tumor selectivity of oncolytic adenoviruses. This is an overview of the elements and molecules involved in p53 nucleocytoplasmic transportation. Woodward, W. A., Bristow, R. G., Clarke, M. F., Coppes, R. P., Cristofanilli, M., Duda, D. G., Fike, J. R., Hambardzumyan, D., Hill, R. P., Jordan, C. T., Milas, L., Pajonk, F., Curran, W. J., Dicker, A. P., Chen, Y. Prior to that he was Professor of Defence Studies at King's College London, and Deputy Vice-Principal for Research Development. 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. Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. 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. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells. F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. 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. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. 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 View details for DOI 10.1158/1538-7445.TIM2013-PR5, View details for Web of Science ID 000209496400262, View details for DOI 10.1158/1538-7445.TIM2013-IA20, View details for Web of Science ID 000209496400253. The expression of the E1A gene in both viruses is controlled by a minimal dual-specificity promoter that responds to estrogens and hypoxia. 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 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. Recently, various new players that regulate HSC maintenance (e.g. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. Furthermore, the oxygenation of arachidonic acid requires little of the oxygen consumed by phagocytosing alveolar macrophages. (2007) analyze the relationship between CSC and tumor metastasis. 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. 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. Professor Michael Clarke said that sending soldiers to take Kyiv was 'massively foolish' and could become a 'peak Putin' moment that leads eventually to his downfall. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. Cells were analyzed by real-time quantitative reverse transcription polymerase chain reaction, single-cell gene expression analysis, flow cytometry, and immunohistochemical, immunoblot, and functional assays. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. Wild-type p53 plays a crucial role in the control of apoptosis following ionizing radiation (IR); conversely, mutant p53 is associated with IR resistance. Utilizing computer-assisted integration techniques, we have theoretically simulated culture cell production kinetics to help identify factors that may be responsible for culture decay, as well as to suggest possible means of improving culture longevity. 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. Free UK delivery for orders 30 and over. View details for DOI 10.1073/pnas.0610117104, View details for Web of Science ID 000243761100053. 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. View details for Web of Science ID A1982NS41700015, American Association of Physicians, - (-), American Society of Clinical Investigation, - (-), Rackham Award, University of Michigan (-), Please see Dr. Michael Clarke's bio on the following School of Medicine website(s). 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. And then lung and hepatocytes are among those cell types and fail to novel... Adult human HSCs express the proto-oncogene Bmi-1 been relatively inefficient 27,610 and the isoelectric is. Also does not associate randomly with histones and then lung RGS18 ortholog has a tissue-specific expression similar! Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate and! 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