professor michael clarke biography

professor michael clarke biography

Mouse RGS18 is expressed from a single gene and shows tissue specific distribution. 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. Stanford is currently not accepting patients for this trial. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. B., Alizadeh, A. Three seminoma patients remain progression-free. View details for Web of Science ID 000079323200036. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. We have designed a microfluidic device to perform sensitive ChIP analysis on low cell numbers in a rapid, automated fashion while preserving the specificity of the assay. He was Director General of the Royal United Services Institute from 2017-2015 and is now a Distinguished Fellow at RUSI. View details for Web of Science ID A1993KD78500072. 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. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. Taken together, these results strongly suggest that the stromal cell layer does produce important factors for active hematopoiesis during its growth to confluence. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors. Ryan, J. J., Prochownik, E., Gottlieb, C. A., Apel, I. J., Merino, R., Nunez, G., Clarke, M. F. CELL-CYCLE ANALYSIS OF P53-INDUCED CELL-DEATH IN MURINE ERYTHROLEUKEMIA-CELLS. View details for Web of Science ID A1995TF89100042. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues. These results indicate that a basic domain other than the well defined NLS is required for the nuclear import of p53. Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood. These results suggest that inhibitors of the TLR2 pathway merit investigation as possible therapeutic and chemoprevention agents. However, the mechanisms regulating p53 subcellular localization remain unclear. 2010). In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. Following his specialty training in medical oncology at Royal Prince Alfred and Westmead Hospitals, Professor Boyer was a Research Fellow and Clinical Fellow at the Ontario Cancer Institute and Princess Margaret Hospital in Toronto, Canada, where he completed his PhD on cell biology. Liu, H., Shimono, Y., Bockhorn, J., Olopade, F., Greene, G., Clarke, M. F. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. 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. 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. Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. 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. This development may play an important role in realizing human gene therapy. View details for DOI 10.1016/j.stem.2016.11.007, View details for PubMedCentralID PMC5341693. Purified RGS18 interacts with the alpha subunit of both G(i) and G(q) subfamilies. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Mini Bio (1) Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies. Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. These results demonstrate that Bcl-XL is capable of protecting cells from p53-mediated apoptosis, and suggest a possible mechanism by which tumors expressing Bcl-XL are able to partly overcome the tumor suppressor functions of p53. Yoo, S., Chandhasin, C., Del Rosario, J. R., Chen, Y. K., Stafford, J., Quake, S., Perabo, F., Clarke, M. F. Pharmacologic characterization of TACH101, a first-in-class KDM4 inhibitor for development as a cancer therapeutic. Michael Clark. These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance. Our study identifies both epithelial-mesenchymal transition (EMT) and active MAPK/ERK signaling in tumors that adapt to oncogenic KrasG12D withdrawal in a novel Trp53-/- breast cancer mouse model. 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. The plasmid vector contains simian virus 40-derived promotor, splice, and polyadenylation sequences as well as a transcription unit for a dihydrofolate reductase cDNA. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. View details for Web of Science ID A1994PC47400008. 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.'. Clarke was interested . Finally, the laboratory is actively pursuing how cancer stem cells self-renew to maintain themselves and escape the genetic constraints on unlimited self-renewal that regulate normal stem cell numbers. His interest is in Stem Cell Biology. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. 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. My research is located in three overlapping fields: (a) linguistic and cultural transfer from Mediterranean Antiquity to the medieval European vernaculars; (b) comparative study of epic and heroic narrative traditions, especially in Greek, Latin, and Babylonian, and of their Celtic and Germanic successors and analogues; (c) semantic Pathways that regulate epigenetic control of stem cell identity are critical to the molecular etiology of cancer. Their scholarship is deepening our understanding of learning while changing policy and practice. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. 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. Although many tumor cell lines undergo apoptosis when p53 is expressed, the T47D transfectants remained viable at temperatures permitting wild-type p53 phenotype. 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. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. 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. Isobe, T., Hisamori, S., Hogan, D. J., Zabala, M., Hendrickson, D. G., Dalerba, P., Cai, S., Scheeren, F., Kuo, A. H., Sikandar, S. S., Lam, J. S., Qian, D., Dirbas, F. M., Somlo, G., Lao, K., Brown, P. O., Clarke, M. F., Shimono, Y. CD47 is a ligand for SIRP, a protein expressed on macrophages and dendritic cells. RNA splicing programs define tissue compartments and cell types at single-cell resolution. The data clearly indicate, however, that the class I and class II components of the major histocompatibility complex are unusually hypermethylated in several T-ALL-derived cell lines, while ATL T-cell lines do not substantially differ in this respect from normal peripheral blood T-cells. Thus understanding the mechanisms that regulate stem cell generation has implications for normal development and disease. The Thy-1+CD24medCD49fhigh phenotype contained the majority of the serially transplantable epithelial cells. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. The Bcl-XL protein is a recently discovered member of the bcl-2 family which has been shown to protect cells from some forms of programmed cell death, but has not yet been implicated in the genesis of human carcinomas. 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. His drumming was basic and, for the most part, appropriate for the Byrds' needs, although he was . Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. Schwartz, R. M., Caldwell, J., Clarke, M. F., Emerson, S. G., Palsson, B. O. INVITRO MYELOPOIESIS STIMULATED BY RAPID MEDIUM EXCHANGE AND SUPPLEMENTATION WITH HEMATOPOIETIC GROWTH-FACTORS. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%-4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). 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. Anaesthesia 2001, 56(5), 486-487. View details for DOI 10.1038/s41586-020-2496-1, View details for Web of Science ID 000485326200019, View details for DOI 10.1158/1538-7445.SABCS18-SY17-02, View details for Web of Science ID 000488129901140, View details for Web of Science ID 000453773601250. 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 contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. 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). Adjunct Associate Professor David Welsh. However, none of the NB cell lines expressed Bcl-xS. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. Inflammation disrupts tissue architecture and function, thereby contributing to the pathogenesis of diverse diseases; the signals that promote or restrict tissue inflammation thus represent potential targets for therapeutic intervention. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. We thus identify stromal cells as cellular coordinators of colon inflammation and suggest their pharmacologic manipulation as a potential means to treat colitis. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. Park, I. K., Qian, D. L., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. 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