Jonathan Karn

karn jonathanDr. Karn is currently the Reinberger Professor of Molecular Biology and Chairman of the Department of Molecular Biology and Microbiology at Case Western Reserve University School of Medicine, and Director of the Case Center for AIDS Research. Dr. Karn’s group is known for their studies of the mechanism of action of the HIV regulatory proteins Tat and Rev. In the early 1990’s they demonstrated that Tat and Rev are both RNA binding proteins and they characterized their interactions with the HIV RNA regulatory elements TAR RNA and RRE in molecular detail. The group’s current research focuses on how HIV enters and exits from latency. A key finding is that HIV latency is due to a combination of epigenetic silencing during memory T-cell differentiation and non-epigenetic restrictions on HIV transcription elongation. As part of their studies of the epigenetic regulation of HIV transcription they discovered that latent HIV proviruses carry facultative heterochromatin which is maintained by the histone methyltransferase EZH2. Another key factor used to maintain HIV latency is the negative elongation factor NELF, which is selectively recruited to the latent HIV provirus and block elongation in the absence of Tat. A second theme in the laboratory concerns studies of how latent HIV proviruses can be reactivated by T-cell receptor signaling. The group has that successive waves of NFkappaB, NFAT and AP-1 are used to sustain HIV transcription initiation. They have also discovered a complementary pathway during T-cell receptor mediated cell activation that increases the availability of the essential Tat co-activator, P-TEFb, and stimulates HIV transcription elongation prior to the synthesis of new Tat protein.

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