This Independent Scientist Award (K02) will provide the candidate the opportunity to develop research expertise in retroviral transcription. The award will permit Dr. Lairmore an intensive period of time to refine his research focus and to devote full time to research. The application describes the candidate's capacity to carry out independent research, his record of publications and grants, and his potential as a scientist in the field of molecular retrovirology. The research plan proposes studies to address fundamental questions about the regulation of cAMP responsive element binding protein (CREB)/activating T-cell factor (ATF) transcription factors in primary T cells. The applicant seeks to understand the transcriptional control of cAMP responsive elements (CREs) in the context of primary T cells by comparing the form and function of CREB/ATF transcription factors that bind HTLV-1 and cellular CREs.
Specific aims of the research plan are: 1) determine the mRNA transcripts and protein isoforms of CREB/ATF proteins in activated CD4+ T- lymphocytes; 2) characterize CRE-binding proteins in activated CD4+ T- lymphocytes; 2) characterize CRE-binding proteins following receptor mediated activation of primary CD4+T-lymphocytes; and 3) test the functional influence of CRE-binding proteins in CRE-mediated transcription. The data from the proposed studies may be useful in identifying potential intracellular targets to enhance understanding of how primary lymphocytes regulate CRE-mediated transcription compared to transformed cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02AI001474-03
Application #
2886068
Study Section
Special Emphasis Panel (ZAI1-PSS-A (M1))
Program Officer
Prograis, Lawrence J
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Silverman, Lee R; Phipps, Andrew J; Montgomery, Andrew et al. (2004) Human T-cell lymphotropic virus type 1 open reading frame II-encoded p30II is required for in vivo replication: evidence of in vivo reversion. J Virol 78:3837-45
Ding, Wei; Kim, Seung-Jae; Nair, Amrithraj M et al. (2003) Human T-cell lymphotropic virus type 1 p12I enhances interleukin-2 production during T-cell activation. J Virol 77:11027-39
Kim, Seung-jae; Ding, Wei; Albrecht, Bjorn et al. (2003) A conserved calcineurin-binding motif in human T lymphotropic virus type 1 p12I functions to modulate nuclear factor of activated T cell activation. J Biol Chem 278:15550-7
Albrecht, Bjorn; D'Souza, Celine D; Ding, Wei et al. (2002) Activation of nuclear factor of activated T cells by human T-lymphotropic virus type 1 accessory protein p12(I). J Virol 76:3493-501
Albrecht, Bjorn; Lairmore, Michael D (2002) Critical role of human T-lymphotropic virus type 1 accessory proteins in viral replication and pathogenesis. Microbiol Mol Biol Rev 66:396-406, table of contents
Ding, Wei; Albrecht, Bjorn; Kelley, Robert E et al. (2002) Human T-cell lymphotropic virus type 1 p12(I) expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells. J Virol 76:10374-82
Zhang, W; Nisbet, J W; Albrecht, B et al. (2001) Human T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein/p300. J Virol 75:9885-95
Richard, V; Lairmore, M D; Green, P L et al. (2001) Humoral hypercalcemia of malignancy: severe combined immunodeficient/beige mouse model of adult T-cell lymphoma independent of human T-cell lymphotropic virus type-1 tax expression. Am J Pathol 158:2219-28
Ding, W; Albrecht, B; Luo, R et al. (2001) Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12(I): association with calreticulin and calnexin. J Virol 75:7672-82
Zhang, W; Nisbet, J W; Bartoe, J T et al. (2000) Human T-lymphotropic virus type 1 p30(II) functions as a transcription factor and differentially modulates CREB-responsive promoters. J Virol 74:11270-7

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