Picture of Donald Coen
Donald Mark Coen, Ph.D.
Professor of Biological Chemistry and Molecular Pharmacology

Our laboratory takes molecular approaches to herpesvirus replication and latency. Current projects focus on the biogenesis, mechanisms of repression, and biological roles of viral microRNAs during HSV infection.

 

Research:

Our laboratory takes molecular approaches to herpesvirus replication and latency.  These studies provide excellent models for biological processes in eukaryotic cells and, because herpesviruses such as herpes simplex virus (HSV) and human cytomegalovirus (HCMV) are important pathogens, to exploit differences between herpesvirus and cellular processes for safe and effective antiviral therapy.   Areas of research include:

Novel post-transcriptional regulatory mechanisms.  Current projects focus on the biogenesis, mechanisms of repression, and biological roles of viral microRNAs during HSV infection.

Herpesvirus DNA replication proteins:  Projects include determining the 3-D structures of these proteins (with the Hogle lab), and the roles of poorly understood structural domains, and exploring their interactions with each other, cellular proteins, and nucleic acids via biochemical, mutational, and biophysical approaches, including (with the Loparo and Golan labs) single molecule methods.   These studies should permit detailed understanding of these complicated proteins and rational drug design.

Nuclear egress:  How do HCMV nucleocapsids move towards and gain access to the inner nuclear membrane, and bud through it?  Projects include biochemical and biophysical studies of a viral enzyme that mimics cyclin-dependent kinase and of a nuclear egress complex (in collaboration with the Hogle lab), and molecular genetic and cell biological studies of these proteins' functions in infected cells.

Drug targets and development of new therapies.   Aside from studies of established drug targets (herpesvirus DNA polymerases and the HCMV protein kinase), projects include discovering new antiviral drugs that inhibit protein-protein interactions, and finding new drug targets by a combination of "chemical genetic" and molecular genetic approaches.

HSV latency/pathogenesis.  HSV forms latent infections that persist for the life of the host.  How this occurs is biologically fascinating and clinically important.  Projects entail molecular genetic, and PCR-basedmethods to explore viral gene regulation especially how viral and host microRNAs repress viral gene expression, thereby maintaining latency.

Address: 

Room SGM - 304

250 Longwood Avenue

Boston, MA 02115

Publications View
SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-?B Activation.
Authors: Authors: Kim ET, Roche KL, Kulej K, Spruce LA, Seeholzer SH, Coen DM, Diaz-Griffero F, Murphy EA, Weitzman MD.
Cell Rep
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Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity.
Authors: Authors: Patel CD, Backes IM, Taylor SA, Jiang Y, Marchant A, Pesola JM, Coen DM, Knipe DM, Ackerman ME, Leib DA.
Sci Transl Med
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Herpes Simplex Virus 1 Lytic Infection Blocks MicroRNA (miRNA) Biogenesis at the Stage of Nuclear Export of Pre-miRNAs.
Authors: Authors: Pan D, Li G, Morris-Love J, Qi S, Feng L, Mertens ME, Jurak I, Knipe DM, Coen DM.
MBio
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HSV-1 DNA polymerase 3'-5' exonuclease-deficient mutant D368A exhibits severely reduced viral DNA synthesis and polymerase expression.
Authors: Authors: Lawler JL, Coen DM.
J Gen Virol
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A Role for Myosin Va in Human Cytomegalovirus Nuclear Egress.
Authors: Authors: Wilkie AR, Sharma M, Pesola JM, Ericsson M, Fernandez R, Coen DM.
J Virol
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Herpes Simplex Virus 1 DNA Polymerase RNase H Activity Acts in a 3'-to-5' Direction and Is Dependent on the 3'-to-5' Exonuclease Active Site.
Authors: Authors: Lawler JL, Mukherjee P, Coen DM.
J Virol
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CCCTC-Binding Factor Acts as a Heterochromatin Barrier on Herpes Simplex Viral Latent Chromatin and Contributes to Poised Latent Infection.
Authors: Authors: Lee JS, Raja P, Pan D, Pesola JM, Coen DM, Knipe DM.
MBio
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Viral Ubiquitin Ligase Stimulates Selective Host MicroRNA Expression by Targeting ZEB Transcriptional Repressors.
Authors: Authors: Lutz G, Jurak I, Kim ET, Kim JY, Hackenberg M, Leader A, Stoller ML, Fekete DM, Weitzman MD, Coen DM, Wilson AC.
Viruses
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Getting to and through the inner nuclear membrane during herpesvirus nuclear egress.
Authors: Authors: Lye MF, Wilkie AR, Filman DJ, Hogle JM, Coen DM.
Curr Opin Cell Biol
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A Small Covalent Allosteric Inhibitor of Human Cytomegalovirus DNA Polymerase Subunit Interactions.
Authors: Authors: Chen H, Coseno M, Ficarro SB, Mansueto MS, Komazin-Meredith G, Boissel S, Filman DJ, Marto JA, Hogle JM, Coen DM.
ACS Infect Dis
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