Distinguished Foundation Professor of Biological Sciences and Chairman

Lewis Hall, #3174b
Office: (757) 446-5662
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Education

• B.A., Pomona College, Claremont, CA
• Ph.D., Yale University, New Haven, CT
• Postdoctoral Training, The Rockefeller University, New York, NY
• Memorial Sloan-Kettering Cancer Center, New York, NY

Prior Positions

• Asst., Assoc. Prof., Cell Biology, The Rockefeller University
• Prof. and Vice-Chair, Pathology, Mount Sinai School of Medicine
• Assoc. Director for Shared Resources, D. H. Ruttenberg Cancer Center, Mount Sinai School of Medicine

Research Interests

Areas of interest: AIDS, DNA replication, neurovirology, virology, environmental carcinogenesis, nucleic acids, cancer, cell cycle, tumor suppressors, lung cancer, chromatin,  gene, transcription, brain pathology, HIV.

Work in the laboratory of Dr. Edward M. Johnson is concerned with control of DNA replication in cancer and AIDS. 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, Pura, are colocalized with once-replicated DNA in S and G2, that Pura modulates activity of Cdk2 and that Pura 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 Pura 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.

Another major 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, Pura. A complex between Tat and Pura 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. Pura is a frequent partner of Cyclin/Cdk complexes, as is another Tat-binding protein, Cyclin T1.

We are exploring the dynamics of the interactions between Tat, T-antigen and Pura during the course of JCV infection of oligodendrocytes and are determining whether transcriptional activation involves activity of Cyclin T1/Cdk9. We are detailing the mechanism by which Tat enhances replication initiated at the JCV origin in human oligodendrocytes both in vivo and using a new in vitro system. We are also examining the ability of TAT and Pura to interact with Smad effectors of the TGF-β pathway. Results will help elucidate pathways of activation of HIV-1 and JCV in the brain and will help target particular molecular interactions for therapy.

The following is a link to a recent interview with Dr. Johnson: http://conversations.org/story.php?sid=174

Our laboratory has generated five patents.

Selected Publications (from >140)

• Wang, L.G., Johnson, E.M., Kinoshita,Y., Babb,J., Buckley, M., Liebes, L., Melamed, J., Liu, X.M., Kurek, R., Ossowski, L., and Ferrari, A.C. (2008) Androgen receptor overexpression in prostate cancer linked to Pura loss from a novel repressor complex. Cancer Res., 68, 2678-2688.
• Weinreb, D.B., Desman, G.T., Amolat-Apiado, M.J.M., Burstein, D.E., Godbold, J.H., Jr. and Johnson, E.M. (2006) Polyoma virus infection is a prominent risk factor for bladder carcinoma in immunocompetent individuals. Diagnostic Cytopath. 34, 201-203.
• Johnson, E.M., Kinoshita, Y., Weinreb, D.B., Wortman, M.J., Simon, R., Khalili, K., Winckler, B.and Gordon, J. (2006) Role of Pura in Targeting mRNA to Sites of Translation in Hippocampal Neuronal Dendrites. J. Neurosci. Res., 83, 929-943.
• Kinoshita Y, Johnson EM. Site-specific loading of an MCM protein complex in a DNA replication initiation zone upstream of the c-MYC gene in the HeLa cell cycle. J. Biol.Chem. 2004; 279(34):35879-89.
• Johnson EM, Kinoshita Y, Daniel DC. A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13. Nucleic Acids Research 2003; 31:2915-2925.
• Johnson EM. The Pur protein family: clues to function from recent studies on cancer and AIDS. Anticancer Research 2003; 23:2093-2100.
• Liu H, Johnson EM. Distinct proteins encoded by alternative transcripts of the PURG gene, located contrapodal to WRN on chromosome 8, determined by differential termination/ polyadenylation. Nucleic Acids Res 2002; 30:2417-2426.
• Barr SM, Johnson EM. Ras-induced colony formation and anchorage-independent growth inhibited by elevated expression of Pura in NIH3T3 cells. J Cell Biochem 2001; 81:621-638.
• Daniel DC, Schiller RJ, Liu H, Wortman MJ, Gan L, Mellen JS, Chang CF, Gallia GL, Khalili K, Johnson EM. Coordinate effects of human immunodeficiency virus type-1 protein, Tat, and cellular protein, Pura , on DNA replication initiated at the JC virus origin. J Gen Virol 2001; 82:1543-1553.
• Lezon-Geyda K, Najfeld V, Johnson EM. Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia. Leukemia 2001; 15:954-962.