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Edward M. M. Johnson , PhD

    • Title:
    • Professor Emeritus

    • Role:
    • Emeritus Faculty

    • Faculty Appointments:
    • 1975-1981   Assistant Professor, The Rockefeller University

      1975-1982   Associate Scientist, Memorial Sloan-Kettering Cancer Center

      1979-1984   Associate Professor, Genetics Field, Cornell Graduate School of Medical Sciences

      1981-1985   Associate Professor, The Rockefeller University

      1985-1992   Adjunct Professor, The Rockefeller University

      1985-2005   Professor, Brookdale Center for Molecular Biology, Mount Sinai School of Medicine

      1985-2005   Professor of Pathology, Mount Sinai School of Medicine

      1996-2005   Professor, Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine

      1999-2005   Vice Chairman for Research, Department of Pathology, Mount Sinai School of Medicine

      2000-2005   Associate Director for Shared Resources, Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine

      2005-2011   Professor and Chairman, Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School

      2006-pres    Foundation Distinguished Professor in the Biological Sciences, Eastern Virginia Medical School

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    • Undergraduate Education:
    • Graduate Education:
      • PhD, Yale University, New Haven, CT
    • Postdoctoral Education:
      • Postdoctoral Training, The Rockefeller University, New York, NY
      • Memorial Sloan-Kettering Cancer Center, New York, NY
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    • Honors and Awards:

      1963-1967    National Merit Scholar

      1971-1973    Jane Coffin Childs Fellowship in Molecular Biology

      1973-1975    Special Fellow of The Leukemia Society of America

      1982-1987    American Cancer Society Faculty Research Award

      1992             Shannon Award, NIH-NCI

      2006             Excellence in Research Award, Eastern Virginia Medical School

      2008-pres     EVMS Foundation Distinguished Professor in Biomedical Sciences

    • Research Interests:
    • Work in the laboratory of Dr. Edward M. Johnson is concerned with control of DNA replication in cancer and AIDS. Dr. Johnson discovered the Pur family of proteins, and work with family member Pur-alpha is the focus of several of the laboratory research projects. An important current project involves an opportunistic infection of the brain, caused by the virus JCV, in AIDS patients. We have hypothesized that activation of JCV in glial cells of the brain is influenced by HIV-1 infection. We have found that JCV late gene transcription is stimulated by the HIV-1 Tat protein through action at sequence elements bound by the cellular protein, Pur-alpha. A complex between Tat and Pur-alpha acts to stimulate transcription at both the HIV-1 TAR RNA element and the JCV late promoter. The complex also interacts with T-antigen to enhance JCV DNA replication. Pur-alpha is a frequent partner of Cyclin/Cdk complexes, as is another Tat-binding protein, Cyclin T1.

      A major project involving lung cancer aims to elucidate the mechanism by which cells distinguish newly- replicated DNA, and its associated proteins, in S and G2 phases of the cell cycle and prevent that DNA from reinitiating replication in the same cycle. A primary hypothesis is that  alterations in activity of an MCM4, 6, 7 helicase complex,  necessary for initiation or reinitiation, are mediated by Cdk-dependent phosphorylation.   We are pursuing findings that Cyclin A/Cdk2 and sequence- specific single-stranded DNA-binding protein, Pur-alpha, are colocalized with once-replicated DNA in S and G2, that Pur-alpha modulates activity of Cdk2 and that  Pur- alpha  colocalizes with MCM7 on chromatin. We shall ascertain using chromatin immunoprecipitation (ChIP) and re-ChIP with successive antibodies the location and timing of assembly and dissociation of MCM4, 6 and 7 helicase components and the helicase inhibitor, MCM2, upstream of the c-MYC gene  in the cell cycle of small-cell lung carcinoma cells and normal controls. We are examining whether Pur-alpha modulates the MCM4, 6, 7 helicase, either by association with Cyclin A/Cdk2 or by DNA unwinding. Results allow identification of links between control of initiation of replication and imposition of checkpoint controls that are critical in preventing progression to cancer.

      Recently we have commenced research on two potentially exciting, related discoveries. We have found that enhanced, intracellular Pur-alpha alleviates certain molecular abnormalities in amyotrophic lateral sclerosis and frontotemporal dementia. We have made a series of peptides that mimic this action of Pur-alpha and are testing them for therapeutic value. We have now discovered that several Pur-alpha binding sites in JC virus are sites of potential recombination with Epstein-Barr virus. We are testing the ability of this novel interviral recombination to alter the JCV control region, helping to drive the virus to neurovirulence in glial cells of the brain.

      Our laboratory has generated five patents.

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