This Physician/Scientist Award is designed to provide a rigorous and thorough scientific training in preparation for a career in academic medicine with intensive basic science research commitment. It combines the superb academic atmosphere at the Whitehead Institute, Massachusetts Institute of Technology, the Harvard Medical School and the Massachusetts General Hospital (MGH). The Phase One sponsor, Dr. David Baltimore, has an impressive enthusiasm for the nurture and training of young physician/ scientists. Phase One will involve an intensive research experience at the Whitehead Institute. At the same time, graduate level course work in molecular genetics, molecular virology and immunology will be conducted at Harvard, M.I.T. and the Marine Biological Laboratory at Woods Hole. In Dr. David Baltimore's laboratory, the research will focus on the understanding of Human immunodeficiency Virus (HIV) replication in the monocyte/macrophage. The extremely complex nature of HIV replication will be investigated using gel retardation assays and DNA protection assays to study cell-specific factors involved in directing the transcription of HIV proteins. An important cell-derived factor, NF Kappa B, which has been shown to be involved in HIV replication in T cell lines, will be studied in the monocyte/macrophage. We will also investigate whether there are genetic differences in a cell tropic versus monocyte/macrophage tropic HIV strains. Restriction enzyme analysis, cloning and nucleotide sequencing of specific HIV isolates with differing cell tropism will be performed to examine whether there exist specific genetic differences in HIV strains within the long terminal repeat and/or the envelope glycoprotein region. A rigorous understanding of HIV production in the monocyte/ macrophage will be key in understanding a variety of the pathogenetic mechanisms of this virus. During this time, the candidate will become familiar with a number of important and generalizable molecular virologic techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
7K11AI000930-03
Application #
3085307
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Project Start
1990-10-01
Project End
1994-04-30
Budget Start
1990-10-01
Budget End
1991-04-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Bagasra, O; Pomerantz, R J (1993) Human immunodeficiency virus type I provirus is demonstrated in peripheral blood monocytes in vivo: a study utilizing an in situ polymerase chain reaction. AIDS Res Hum Retroviruses 9:69-76
Bagasra, O; Seshamma, T; Oakes, J W et al. (1993) High percentages of CD4-positive lymphocytes harbor the HIV-1 provirus in the blood of certain infected individuals. AIDS 7:1419-25
Bagasra, O; Seshamma, T; Oakes, J W et al. (1993) Frequency of cells positive for HIV-1 sequences assessed by in situ polymerase chain reaction. AIDS 7 Suppl 2:S7-10
Bagasra, O; Seshamma, T; Pomerantz, R J (1993) Polymerase chain reaction in situ: intracellular amplification and detection of HIV-1 proviral DNA and other specific genes. J Immunol Methods 158:131-45
Winslow, B J; Pomerantz, R J; Bagasra, O et al. (1993) HIV-1 latency due to the site of proviral integration. Virology 196:849-54
Bagasra, O; Wright, S D; Seshamma, T et al. (1992) CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide. Proc Natl Acad Sci U S A 89:6285-9
Seshamma, T; Bagasra, O; Oakes, J W et al. (1992) A quantitative reverse transcriptase-polymerase chain reaction for HIV-1-specific RNA species. J Virol Methods 40:331-45
Taylor, J P; Pomerantz, R; Bagasra, O et al. (1992) TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J 11:3395-403
Pomerantz, R J; Bagasra, O; Baltimore, D (1992) Cellular latency of human immunodeficiency virus type 1. Curr Opin Immunol 4:475-80
Bagasra, O; Khalili, K; Seshamma, T et al. (1992) TAR-independent replication of human immunodeficiency virus type 1 in glial cells. J Virol 66:7522-8

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