Edward M. Johnson, PhD

<ul>
<li>PhD, Yale University, New Haven, CT</li>
</ul>

Professor Emeritus

Microbiology and Molecular Cell Biology



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

2006-2016   Foundation Distinguished Professor in the Biological Sciences, Eastern Virginia Medical School

2017-           Professor Emeritus

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

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.

Presentations and Scholarships

Link to Publications on NCBI

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

2006-2016   Foundation Distinguished Professor in the Biological Sciences, Eastern Virginia Medical School

2017-           Professor Emeritus

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

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.

Presentations and Scholarships

Link to Publications on NCBI

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