Virology Faculty Member - Donald Coen

Donald Coen

Professor of Biological Chemistry and Molecular Pharmacology

Harvard Medical School
BCMP, Seeley G. Mudd Bldg., Rm. 304A
250 Longwood Avenue
Boston, MA 02115
Tel: 617-432-1691
Fax: 617-432-3833
Email: don_coen@hms.harvard.edu



We take molecular approaches to herpesviruses, in part to understand processes that distinguish viral functions from cellular functions, which can be exploited to permit antiviral therapy. The foci are 1) post-transcriptional regulation of gene expression, 2) functional dissection of replication proteins, 3) analysis of virus latency, a fascinating and clinically
important topic, 4) antiviral drug targets, drug mechanisms, and drug resistance, with emphasis on targeting proteins involved in nuclear egress.

Novel post-transcriptional regulatory mechanisms: We are studying post-transcriptional regulation of herpes simplex virus genes, including microRNAs, regulated polyadenylation, ribosomal frameshifting, internal ribosome entry sites, and translational regulation.

Herpesvirus DNA replication proteins: These proteins are both antiviral drug targets and prototypes for human replication proteins. We are currently focusing on determining the 3-D structures of these proteins (with the Hogle lab) and exploring their interactions with each other and nucleic acids via biochemical, mutational, and biophysical approaches, including
(with the Golan and van Oijen labs) single molecule methods. These studies should permit detailed understanding of these complicated proteins and the process of viral DNA replication, and rational drug design.

Latency and pathogenesis: We use virus mutants, PCR-based methods, and microarray technologies to explore viral and neuronal gene function and regulation (e.g. how viral gene expression is repressed by microRNAs) during latency and mechanisms by which drug resistant mutants retain pathogenicity.

Drugs and nuclear egress: Aside from our studies of herpesvirus DNA replication proteins. we are studying the human cytomegalovirus protein kinase that phosphorylates ganciclovir and is inhibited by maribavir. We have found that this enzyme mimics cyclin-dependent kinases in phosphorylation of nuclear lamins and retinoblastoma protein. Our current
studies include investigating how it and other viral proteins promote nuclear egress of nucleocapsids, and targeting this process for antiviral drug discovery, especially by screening chemical libraries and structure-based studies (with the Hogle lab).



Last Update: 10/22/2013



Publications

For a complete listing of publications click here.

 


 

Kramer MF, Cook WJ, Roth FP, Zhu J, Holman H, Knipe DM, Coen DM. Latent herpes simplex virus infection of sensory neurons alters neuronal gene expression. J Virol 2003; 77:9533-9541.

Appleton BA, Loregian A, Filman DJ, Coen DM, Hogle JM. The cytomegalovirus DNA polymerase subunit UL44 forms a C-clamp shaped dimer. Mol Cell 2004; 15; 233-244.

Griffiths A, Coen DM. A novel internal ribosome entry site in the herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci USA; 2005; 102:9667-9772.

Loregian A, Coen DM. Selective anti-cytomegalovirus compounds discovered by screening for inhibitors of subunit interactions of the viral polymerase. Chem Biol 2006; 13:191-200.

Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, Wang X-J, Coen DM. Prediction and identification of herpes simplex virus 1-encoded microRNAs. J Virol 2006; 80:5499-5508.

Hume AJ, Finkel JS, Kamil JP, Coen DM, Culbertson MR, Kalejta, RF. Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 2008; 320:797-799.



© 2013 by the President and Fellows of Harvard College