 |
George
Blanck, Ph.D. E-mail:
gblanck@hsc.usf.edu |
Training
Undergraduate:
University of Pennsylvania
Ph.D.: Columbia University
Postdoctoral Fellow: Harvard University
Research Interests
Our lab's long-term goals have been (i) to further understand molecular mechanisms of gene regulation and (ii) to further understand disease processes as they relate to pathological conditions of gene regulation.
To meet these goals, our lab is primarily dedicated toward the understanding of the interferon cell-signaling pathway in normal and tumor cells. The activation of this pathway leads to the expression of genes that inhibit tumor cell growth by at least several mechanisms. Consequently, tumors develop with defects in this pathway. We are in the process of using transgenic and knock-out mice to isolate specific branches of the inteferon pathway to determine exactly which consequences of the tumor defects are relevant to tumor development in tumor prone mice. Also, because of these tumor defects in inteferon mediated cell-signaling, human tumor cell lines represent tools for understanding the normal biochemical mechanisms of the signaling pathway. We have taken advantage of numerous tumor cell lines, defective for interferon signaling, to determine that proteins, not previously known to be relevant to this pathway's function, are indeed required for normal activation of the pathway. Most recently, this work has led to a novel mechanism of gene repression, involving a protein complex we have termed a "repressosome", representing a concept that will likely be applicable to other genes. As another example, we have learned that two proteins that were previously thought to have opposing effects in gene activation can instead cooperate in the activation of a gene. This led to the discovery of novel biochemical features of gene activation for these two proteins, termed IRF-1 and IRF-2.
We regard to both the repressosome and the IRF proteins, we expect that a more detailed understanding of the biochemical features of these protein complexes will allow drugs to be designed to mitigate disease processes. The repressosome is likely to be very specific for a particular gene that is not expressed in tumor cells. The re-expression of this gene could make the tumor cells less tumorigenic, thus drugs designed to disrupt the repressosome may reduce tumor burden. Small, cell-permeable molecules, related to drugs currently in use in medicine, have already been used to disrupt the repressosome. This disruption is accompanied by the re-establishment of specific gene expression. We have also recently learned that the IRF-2 protein is important in mice for interferon signaling, thus verifying that what we discovered in the experimental setting of cultured cells is applicable to a whole organism. Because of this result, we expect that IRF-2 will be a good drug target for mitigating immunity associated pathological conditions where the gene activated by IRF-2 is over-expressed, such as in autoimmunity or organ transplant rejection. Current drugs designed to meet this goal target broad aspects of the immune system leading to undesirable consequences, for example tumor development in transplant patients receiving immunosuppressive drugs. Thus, novel approaches to immunosuppression is an important goal.
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for publications by: 
This
search will be conducted at the US National Library of Medicine (NLM) and PubMed.
Selected
Publications
Osborne, A.R., Zhang, H., Fejer, G., Palubin, K.M., Niesen, M.I., and Blanck, G. Oct-1 maintains an intermediate, stable state of HLA-DRA promoter repression in Rb-defective cells: an Oct-1-containing repressosome that prevents NF-Y binding to the HLA-DRA promoter. Journal of Biological Chemistry 279 (28): 28911-28919 (2004).
Blanck, G. Mutations and regulatory anomalies effecting tumor cell immune functions. Cancer Immunology Immunotherapy 53 (1): 1-16 (2003).
D. D. Eason, C. Lebron, D. Coppola, L. C. Moscinski, S. Livingston, E. T. Sutton, and G. Blanck. Development of CD30+ lymphoproliferative disease in mice lacking interferon regulatory factor-1. Oncogene 22 (40): 6166-6176 (2003).
H. Xi and G. Blanck. The IRF-2 DNA binding domain facilitates the activation of the class II transactivator (CIITA) Type IV Promoter by IRF-1. Molecular Immunology 39(11): 677-684 (2003).
George Blanck. Components of the IFN-g signaling pathway in tumorigenesis. Achivum Immunologiae and Therapiae Experimentalis 50(3):151-158 (2002).
A. Osborne, H. Zhang, W. Yang, E. Seto, and G. Blanck. Histone deacetylase activity represses gamma-interferon inducible HLA-DR gene expression following the establishment of a DNase I-hypersensitive chromatin conformation. Molecular and Cellular Biology 21(19): 6495-6506 (2001).
D. D. Eason, D. Coppola, S. Livingston and G. Blanck. Loss of MHC class II inducibility in hyperplastic tissue of in Rb-defective mice. Cancer Letters 171(2): 209-214 (2001).
B. L. Goodwin, H. Xi, R. Tejiram, D. D. Eason, N. Ghosh, K. L. Wright, U. Nagarajan , J. M. Boss, G. Blanck. Varying functions of specific MHC class II transactivator (CIITA) Promoter III and IV elements in melanoma cell lines. Cell Growth and Differentiation 12(6): 327-335, (2001).
H. Xi, B. Goodwin, A. T. Shepherd, and G. Blanck. Impaired Class II Transactivator Expression in Mice Lacking IRF-2. Oncogene 20(31): 4219-4227 (2001).
D. D. Eason and G. Blanck. High level class II trans-activator induction does not occur with transient activation of the interferon gamma signaling pathway. Journal of Immunology 166(2): 1041-1048, (2001)
H. Zhang, S. Wei, J. Sun, D. Coppola, B. Zhong, G. D. Wu, B. Goodwin, S. Sebti, J. Y. Djeu, and G. Blanck. Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice. Cell Growth and Differentiation 11:635-639, (2000).
H. Xi and G. Blanck. Interferon regulatory factor-2 point mutations in human pancreatic tumors. International Journal of Cancer 87(6): 803-808, (2000).
Cancer Biology Ph.D. Program
H. Lee Moffitt Cancer Center, MRC-4 East
12902 Magnolia Drive
Tampa, Florida 33612
Phone: 813-745-6876
E-mail: CancerPHD@moffitt.org
Copyright © 2000 University of South Florida