Look at this paper! Anyone can repeat it?
Nature. 1998 Nov
Proto-oncogene PML controls genes devoted to MHC class I antigen
Zheng P, Guo Y, Niu Q, Levy DE, Dyck JA, Lu S, Sheiman LA, Liu Y.
Department of Pathology and Kaplan Comprehensive Cancer Center, New York
University Medical Center, New York 10016, USA.
Fragments of foreign antigens associated with class I molecules of the major
histocompatibility complex (MHC) are presented at the cell surface to elicit an
immune response. This presentation requires the coordinated expression of
several genes contained in the MHC, including those encoding the MHC class I
heavy chain, the proteins LMP-2 and LMP-7, which are involved in the proteasomal
degradation of cytosolic antigens into peptide fragments that are destined for
association with MHC class I molecules, and TAP-1 and TAP-2, which transport
these fragments across the membrane of the endoplasmic reticulum at the start of
their journey to the cell surface. In many virus-transformed cell lines and
spontaneous tumours, these genes are simultaneously repressed. However, the key
factor(s) that are essential for their expression and repression have not been
identified. Here we report that the proto-oncogene product PML induces
expression of LMP-2, LMP-7, TAP-1 and TAP-2 in an MHC-class I-negative,
recurrent tumour, leading to the re-expression of cell-surface MHC in tumours
and to rejection of the tumours. PML also regulates MHC expression in
untransformed fibroblasts. We conclude that malfunction of PML may enable a
tumour to evade the immune defence of its host.
[PubMed - indexed for MEDLINE]
But this has crossed the line of scientific criminality in that this individual has deceived several laboratory groups into altering the focus of their research based upon his fabrications. A graduate student within the laboratory group has lost valuable time pursuing a path to a dead end. Research funds---hard to find at any given time and in most every case--have been squandered by those misled by the deception.
While JCB was only out for five months before it was retracted, the falsifications derailed the research of another graduate student in Grosevldâ€™s lab who was following up on Boisâ€™s findings, Grosveld said. â€œMy graduate student spent a whole year frustrated to the bone because he couldnâ€™t replicate any of it.â€쳌
Look at what NIH grant derived from this paper had yieldedï¼š
HowÂ many publications are related to the NIH RO1 grants? How many students and postdoctroal researchers wasted their time? The PI knows!!!
Grant Detail The grant detail shows the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the fingerprint of the grant. If any publications referencing this grant are found in the data, they will be listed here as well. PROTO ONCOGENE PML AND TUMOR EVASION OF HOST IMMUNITYPan Zheng 6 August 1999 - 31 May 2004
NATIONAL CANCER INSTITUTE NIH RePORTERAbstractThe peptides presented by the major histocompatibility complex (MHC) class I antigens are the primary targets on tumor cells for immune recognition by host cytotoxic T lymphocytes (CTL). A large proportion of tumors derived from MHC class I positive epithelia have total or selective loss of cell surface MHC class I expression. This may allow tumors to evade the immune recognition by avoiding MHC class I antigen presentation. While genetic mechanisms that lead to antigen presentation defects are largely unknown, it is clear that expression of multiple genes involved in antigen presentation such as those encode transporters for peptides across endoplasmic reticulum (ER) membrane (TAP-1 and TAP-2), proteosome components LMP-2 and LMP-7 are affected. We have recently characterized a recurrent tumor in mouse that had defective expression of TAP1/2 and LMP2/7. Expression cloning revealed that the defect could be complemented by overexpression of proto-oncogene PML-F12. Moreover, we have found that endogenous PML contains a dominant negative mutation. The main goal of the proposed study is to establish whether malfunction of PML is responsible for antigen presentation defects in murine and human tumors. We proposed to investigate the mechanisms by which PML controls multiple genes devoted to MHC class I antigen processing. Our proposed study is fundamental to understand the basic mechanism for tumor evasion of host anti-tumor immunity. Given expression of PML gene in normal tissue, it is likely the mechanism we have identified is involved in antigen presentation in normal tissue. As such, our study may establish PML as a master regulator controlling MHC class I antigen presentation.19 Resulting Publications1.2008
McNally Beth A; Trgovcich Joanne; Maul Gerd G; Liu Yang; Zheng PanA role for cytoplasmic PML in cellular resistance to viral infection.PloS one 2008;3(5):e2277.
Wang Yin; Liu Yan; Wu Cindy; Zhang Huiming; Zheng Xincheng; Zheng Zhi; Geiger Terrence L; Nuovo Gerard J; Liu Yang; Zheng PanEpm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling.Cancer cell 2006;10(3):179-90.
Yang Tianyu; Lapinski Philip E; Zhao Haotian; Zhou Qunmin; Zhang Huiming; Raghavan Malini; Liu Yang; Zheng PanA rare transporter associated with antigen processing polymorphism overpresented in HLAlow colon cancer reveals the functional significance of the signature domain in antigen processing.Clinical cancer research : an official journal of the American Association for Cancer Research 2005;11(10):3614-23.
Zheng Xincheng; Yin Lijie; Liu Yang; Zheng PanExpression of tissue-specific autoantigens in the hematopoietic cells leads to activation-induced cell death of autoreactive T cells in the secondary lymphoid organs.European journal of immunology 2004;34(11):3126-34.
Gao Jian-Xin; Chang Xing; Zheng Xincheng; Wen Jing; Yin Lijie; Du Peishuang; Zheng Pan; Liu YangA new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen.International immunology 2004;16(10):1403-9.
Gao Jian-Xin; Liu Xingluo; Wen Jing; Caligiuri Michael A; Stroynowski Iwona; Zheng Pan; Liu YangTwo-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells.Blood 2003;102(13):4456-63.
Sarma Supria; Bai Xue-Feng; Liu Jin-qing; May Kenneth F; Zheng Pan; Liu YangOn the role of unmutated antigens in tumor rejection in mice with unperturbed T-cell repertoires.Cancer research 2003;63(18):6051-5.
Liu Xingluo; Gao Jian Xin; Wen Jing; Yin Lijie; Li Ou; Zuo Tao; Gajewski Thomas F; Fu Yang-Xin; Zheng Pan; Liu YangB7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism.The Journal of experimental medicine 2003;197(12):1721-30.
Gao Jian-Xin; Liu Xingluo; Wen Jing; Zhang Huiming; Durbin Joan; Liu Yang; Zheng PanDifferentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse.Journal of immunology (Baltimore, Md. : 1950) 2003;170(12):5927-35.
Bai Xue-Feng; Liu Jinqing; Li Ou; Zheng Pan; Liu YangAntigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes.The Journal of clinical investigation 2003;111(10):1487-96.
Yang Tianyu; McNally Beth A; Ferrone Soldano; Liu Yang; Zheng PanA single-nucleotide deletion leads to rapid degradation of TAP-1 mRNA in a melanoma cell line.The Journal of biological chemistry 2003;278(17):15291-6.
Zhang Huiming; Melamed Jonathan; Wei Ping; Cox Karen; Frankel Wendy; Bahnson Robert R; Robinson Nikki; Pyka Ron; Liu Yang; Zheng PanConcordant down-regulation of proto-oncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer.Cancer immunity : a journal of the Academy of Cancer Immunology 2003;3():2.
Zheng Xincheng; Gao Jian-Xin; Zhang Huiming; Geiger Terrence L; Liu Yang; Zheng PanClonal deletion of simian virus 40 large T antigen-specific T cells in the transgenic adenocarcinoma of mouse prostate mice: an important role for clonal deletion in shaping the repertoire of T cells specific for antigens overexpressed in solid tumors.Journal of immunology (Baltimore, Md. : 1950) 2002;169(9):4761-9.
May Kenneth F; Chen Lieping; Zheng Pan; Liu YangAnti-4-1BB monoclonal antibody enhances rejection of large tumor burden by promoting survival but not clonal expansion of tumor-specific CD8+ T cells.Cancer research 2002;62(12):3459-65.
Bai Xue-Feng; Liu Jinqing; May Kenneth F; Guo Yong; Zheng Pan; Liu YangB7-CTLA4 interaction promotes cognate destruction of tumor cells by cytotoxic T lymphocytes in vivo.Blood 2002;99(8):2880-9.
Gao Jian-Xin; Zhang Huiming; Bai Xue-Feng; Wen Jing; Zheng Xincheng; Liu Jinqing; Zheng Pan; Liu YangPerinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells.The Journal of experimental medicine 2002;195(8):959-71.
Liu X; Bai X F; Wen J; Gao J X; Liu J; Lu P; Wang Y; Zheng P; Liu YB7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo.The Journal of experimental medicine 2001;194(9):1339-48.
Bai X F; Bender J; Liu J; Zhang H; Wang Y; Li O; Du P; Zheng P; Liu YLocal costimulation reinvigorates tumor-specific cytolytic T lymphocytes for experimental therapy in mice with large tumor burdens.Journal of immunology (Baltimore, Md. : 1950) 2001;167(7):3936-43.
2001Bai X F; Gao J X; Liu J; Wen J; Zheng P; Liu YOn the site and mode of antigen presentation for the initiation of clonal expansion of CD8 T cells specific for a natural tumor antigen.Cancer research 2001;61(18):6860-7.http://www.experts.scival.com/umichig...