Abstract

The specific goals of the research component of this proposal are to define the interactions of the functional genes in the human alpha globin gene cluster. Phase I studies will attempt to define and optimize experimental systems in which to study the expression of these genes and in Phase II these studies will be extended to deal with specific mechanisms of gene control including; position effects, transcriptional interference, 3' control elements (transcriptional termination signals and enhancers), and the general impact of one genes transcription upon the function of other genes in the cluster. The results will be related to the mechanisms of globin gene switching and general mechanisms of gene control in tightly spaced clusters. The training which is planned, and the specific experimental system to be explored are designed to interact and provide that applicant with a firm background for future independent work.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
1K11HL002229-01
Application #
3087603
Study Section
Research Manpower Review Committee (MR)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Haidar, M A; El-Hajj, H; Bueso-Ramos, C E et al. (1997) Expression profile of MDM-2 proteins in chronic lymphocytic leukemia and their clinical relevance. Am J Hematol 54:189-95
Manshouri, T; Yang, Y; Lin, H et al. (1997) Downregulation of RAR alpha in mice by antisense transgene leads to a compensatory increase in RAR beta and RAR gamma and development of lymphoma. Blood 89:2507-15
Bueso-Ramos, C E; Manshouri, T; Haidar, M A et al. (1996) Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat 37:179-88
Haidar, M A; Cao, X B; Manshouri, T et al. (1995) p16INK4A and p15INK4B gene deletions in primary leukemias. Blood 86:311-5
Bueso-Ramos, C E; Manshouri, T; Haidar, M A et al. (1995) Multiple patterns of MDM-2 deregulation in human leukemias: implications in leukemogenesis and prognosis. Leuk Lymphoma 17:13-8
Loya, F; Yang, Y; Lin, H et al. (1994) Transgenic mice carrying the erythropoietin gene promoter linked to lacZ express the reporter in proximal convoluted tubule cells after hypoxia. Blood 84:1831-6
Bueso-Ramos, C E; Yang, Y; deLeon, E et al. (1993) The human MDM-2 oncogene is overexpressed in leukemias. Blood 82:2617-23
Albitar, M; Cash, F E; Peschle, C et al. (1992) Developmental switch in the relative expression of the alpha 1- and alpha 2-globin genes in humans and in transgenic mice. Blood 79:2471-4
Albitar, M; Care, A; Peschle, C et al. (1992) Developmental switching of messenger RNA expression from the human alpha-globin cluster: fetal/adult pattern of theta-globin gene expression. Blood 80:1586-91
Tang, W; Luo, H Y; Albitar, M et al. (1992) Human embryonic zeta-globin chain expression in deletional alpha-thalassemias. Blood 80:517-22

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