professor michael clarke biography

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Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. 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. Michael Clarke is a British academic who specialises in defence studies. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. 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. These findings have important implications for the development and evaluation of oncologic therapies and present opportunities for potential gains in patient outcome. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. View details for Web of Science ID 000186230600042, View details for PubMedCentralID PMC2614897, View details for Web of Science ID 000184162600127. Effect of ASXL1 on the stemness of colorectal cancer initiating cells. Hernandez-Alcoceba, R., Pihalja, M., Qian, D. L., Clarke, M. F. Differential gene expression profiling of adult murine hematopoietic stem cells. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. Research Expertise and Interests Previous studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis. His laboratory is pursuing the identification of cancer stem cells in other tumors so that they can be studied. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. 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. This technology may provide a solution to the need for a high sensitivity, rapid, and automated ChIP assay, and in doing so facilitate the use of ChIP for many interesting and valuable applications. 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. Hisamori, S., Dalerba, P., Shimono, Y., Rothenberg, M. E., Zabara, M., Cai, S., Qian, D., Clarke, M. F. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. One of these, the goblet cells, contained a distinct cKit/CD117(+) crypt base subpopulation that expressed Dll1, Dll4, and epidermal growth factor, similar to Paneth cells, which were also marked by cKit. 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. 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. 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. This will allow the characterization of crucial signaling pathways involved in processes such as self-renewal that are critical for tumor formation by the cancer cells within de novo tumors. View details for Web of Science ID 000079323200036. Clarke M, Mitchell KW, Goodship J, McDonnell S, Barker MD, Griffiths ID, McKie N. Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism. George Malcolm (1917-1997), Pianist, Cembalist, Dirigent und Komponist. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. Wild-type p53 plays a crucial role in the control of apoptosis following ionizing radiation (IR); conversely, mutant p53 is associated with IR resistance. 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. Associate Professor of Instruction; PhD. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The amine-derivatized biotinylated GM-CSF analogues retained biological activity, could specifically label cell surface receptors, and may be useful nonradioactive probes with which to study GM-CSF receptor cytochemistry and receptor modulation by flow cytometry. Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. - Associate Professor: Business Management The rapid medium exchange combined with the addition of human hematopoietic CSFs significantly enhances the proliferation and differentiation of LTBMCs. The Department of Adolescent and Young Adult Medicine's multidisciplinary team includes adolescent physicians, clinical nurse consultant, social worker, clinical psychologist, occupational therapist, dietitian and experienced ward nurses. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. 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. A basic domain, Lys(305)-Arg(306), is required for p53 nuclear import, and a carboxyl-terminal domain, namely the cytoplasmic sequestration domain (CSD) from residues 326-355, could block the nuclear import of Lys(305) or Arg(306) mutated p53. In approaching the bone marrow culture system, we recognize the critical role that hematopoietic growth factors (HGFs) play in hematopoiesis. 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. Professor, Philosophy; Associate Professor, Classics npappas@gc.cuny.edu John D. Greenwood Deputy Executive Officer and Professor, Philosophy; Professor, Psychology +1 212-817-8617 jgreenwood@gc.cuny.edu Natile Clarke Assistant Program Officer, Philosophy +1 212-817-8623 nclarke@gc.cuny.edu Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro. IL-10 function is required for the full protective effect of small-molecule Hedgehog pathway activation in colitis; this pharmacologic augmentation of Hedgehog pathway activity and stromal IL-10 expression are associated with increased presence of CD4(+)Foxp3(+) regulatory T cells. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. 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. An alternately spliced c-myb mRNA encodes a truncated version of p75c-myb (mbm2) that includes the DNA binding region and nuclear localization signal present in the c-myb protein, but does not contain the transcriptional regulatory regions. Han, J. S., Qian, D. L., Wicha, M. S., Clarke, M. F. Targeting cancer cell death with a bcl-x(s) adenovirus. It is clear that new approaches are needed to treat these diseases. Therapeutic Implications of the Cancer Stem Cell Hypothesis, Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. The prognostic power of the IGS was increased when combined with the wound-response (WR) signature.The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. 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 adequate tissue for cancer stem cell quantification. Knockdown of KIT decreased proliferation of colon cancer cell lines and growth of xenograft tumors in mice compared with control cells. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. The conditional expression of lethal genes in tumor cells is a promising gene therapy approach for the treatment of cancer. View details for DOI 10.1056/NEJMoa1506597, View details for Web of Science ID 000368404800006, View details for PubMedCentralID PMC4784450. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. 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. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). 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. Herrema I, Clarke M. Anaesthesia for retinoblastoma screening - a dilemma. 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. These results suggest that LEFTY1 is an endogenous dual-SMAD inhibitor and that suppressing its function may represent a therapeutic vulnerability in breast cancer. View details for Web of Science ID 000083623000026. 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. In order to better understand HSC self-renewal, we need to understand how these pathways are coordinated. Filter By. The stem cells maintain themselves through a process known as self-renewal. He has also acted as a reviewer for the EPSRC and for funding councils in Austria, Finland, France and Germany. 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. Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. In contrast, C5-bGM-CSF binding above background fluorescence could not be detected using this system, suggesting that this derivative could bind to and activate the receptor, but not simultaneously bind fluorescein-conjugated avidin. These latter cell lines do express HLA-DR alpha-mRNA, as well as HLA-DR surface antigens. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. Importantly, infection with the bcl-xS adenovirus resulted in rapid loss of cell viability, DNA fragmentation, and morphological features of apoptosis even in NB cells transfected to overexpress Bcl-2 and Bcl-xL. View details for DOI 10.1146/annurev.cellbio.22.010305.104154, View details for Web of Science ID 000250896200025. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. Professor Michael Clarke 16 August 2021 9 Minute Read Share The tragedy in Afghanistan offers a sobering story for the UK, as it embarks on its 'Global Britain' future in the 2020s. Traditional methods of implementing this assay are lengthy, cumbersome and require a large number of cells, making it difficult to study rare cell types such as certain cancer and stem cells. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. A., Visser, B., Hisamori, S., Shimono, Y., Van De Wetering, M., Clevers, H., Clarke, M. F., Quake, S. R. Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells. View details for DOI 10.1016/j.cell.2006.03.011, View details for Web of Science ID 000237241400007. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. 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. This observation is traditionally explained by postulating variations in tumor microenvironment and coexistence of multiple genetic subclones, created by progressive and divergent accumulation of independent somatic mutations. 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. 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. View details for Web of Science ID A1991FC72500007. Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. 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. 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. We examined the effect of this limited adenovirus replication in vitro and in vivo. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. View details for Web of Science ID A1984TY56600006. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. View details for Web of Science ID A1995RP92400014. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. We have examined the effects of conditionally expressing wild-type p53 activity in HT29 cells on DNA damage and cytotoxicity caused by exposure to fluorodeoxyuridine (FdUrd). Down's syndrome results from full or partial trisomy of chromosome 21. Bcl11b maintains the long-term mammary stem cell and is crucial for drug resistance in breast cancer. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. Interestingly, phytohemagglutin-stimulated leukocyte-conditioned medium stimulated LTHMBCs in a similar fashion, as did conditioned medium from early LTHBMCs. Investigating mechanisms of cancer stern cell radioresistance. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q). Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. They discuss the increasing threat of China, the post-Brexit identity of "Global Britain" and how the . Southern blots of DNA from HTLV-infected cells digested with the methylation-sensitive restriction enzyme HpaII showed that the proviral DNA was methylated in all of the uncultured peripheral blood cells tested. These results demonstrate the feasibility of using continuous perfusion bioreactors as a method of efficiently modifying human hematopoietic stem cells. Ad5ERE2 is able to kill ER(+) human breast cancer cell lines as efficiently as the wild-type virus, but has decreased capacity to affect ER(-) cells. Single cell transcriptomics is revolutionising our understanding of tissue and disease heterogeneity, yet cell type identification remains a partially manual task. Mcl1, Tel/Etv6, Gfi1, Pten and Stat5) have been identified. Biography. The enhanced cytotoxicity was restricted to antibody-coated tumor cells. 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. View details for DOI 10.1126/science.aax0249. 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. 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. 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). We investigated the role of the RTK KIT in development of human colon cancer.An array of 137 patient-derived colon tumors and their associated xenografts were analyzed by immunohistochemistry to measure levels of KIT and its ligand KITLG. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. 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