Mary-Louise Hammarskjold, MD, PhD
Graduate School: Karolinska, Sweden
Primary Appointment: Professor, Microbiology, Immunology, and Cancer Biology
Post Transcriptional Gene Regulation and the Molecular Biology of Human Retroviruses
Email Address: email@example.com
Many mammalian and viral genes are alternatively spliced and subject to regulation at the post- transcriptional level. However, relatively little is known about the cellular mechanisms for this regulation. We are using retroviruses as model systems to elucidate these mechanisms. Some of our studies focus on HIV Rev, an essential HIV protein. Rev mediates the nucleo-cytoplasmic export of unspliced and incompletely spliced HIV RNAs and provides an important HIV drug target. Another major focus of the laboratory is the function of the constitutive transport element (CTE). The CTE interacts directly with host cell proteins to facilitate export of intron containing RNA.
We are currently analyzing the function of cellular proteins that are involved in the CTE mediated export pathway. One is NXF1 (TAP), a protein which has been proposed to play an essential role in cellular mRNA export. A second protein under study is NXT1, an important TAP cofactor. CTE function is also enhanced by SAM68, a major target of Src and Src family kinases and a potential tumor suppressor. Our studies are aimed at identifying the mechanism by which SAM68 promotes CTE function and the role that this protein plays in cellular gene regulation.
Coyle JH, Bor YC, Rekosh D, Hammarskjold ML. The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA. 2011 Jul;17(7):1344-56. doi: 10.1261/rna.2616111. Epub 2011 May 25.
Hammarskjold MH, Rekosh D. A long-awaited structure is rev-ealed. Viruses. 2011 May;3(5):484-92. doi: 10.3390/v3050484.
Shuck-Lee D, Chang H, Sloan EA, Hammarskjold ML, Rekosh D. Single-nucleotide changes in the HIV Rev-response element mediate resistance to compounds that inhibit Rev function. J Virol. 2011 Apr;85(8):3940-9. doi: 10.1128/JVI.02683-10. Epub 2011 Feb 2.
Ward AM, Rekosh D, Hammarskjold ML. Trafficking through the Rev/RRE pathway is essential for efficient inhibition of human immunodeficiency virus type 1 by an antisense RNA derived from the envelope gene. J Virol. 2009 Jan;83(2):940-52. doi: 10.1128/JVI.01520-08. Epub 2008 Oct 29.
Shuck-Lee D, Chen FF, Willard R, Raman S, Ptak R, Hammarskjold ML, Rekosh D. Heterocyclic compounds that inhibit Rev-RRE function and human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother. 2008 Sep;52(9):3169-79. doi: 10.1128/AAC.00274-08. Epub 2008 Jul 14.
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