Department of
Biological Chemistry & Molecular Pharmacology

Don Coen

Professor
Telephone: 
617-432-1691
Fax: 
617-432- 3833
Address: 
Room SGM - 304
Address: 
250 Longwood Avenue
Address: 
Boston MA 02115
Research Areas

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 roles of viral microRNAs and unusual translational mechanisms during HSV infection. 

Herpesvirus DNA replication proteins:  Projects include determining the 3-D structures of these proteins (with the Hogle lab) and exploring their interactions with each other, cellular proteins, 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 rational drug design.

Nuclear egress:  How do HCMV nucleocapsids 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-based and microarray methods to explore viral gene regulation especially how microRNAs repress viral gene expression, thereby maintaining latency, and neuronal genes whose expression is altered during viral latency.

Publications: 

Umbach J, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature; 2008; 454:780-785.

Komazin-Meredith G, Mirchev, R, Golan, DE, van Oijen AM, Coen DM. Hopping of a processivity factor on DNA revealed by single molecule assays of diffusion. Proc Natl Acad Sci USA; 2008; 105:10721-10726.

Hamirally S, Kamil JP, Ndassa-Colday YM, Lin AJ, Jahng WJ, Baek M-C, Noton S, Silva LA, Simpson-Holley M, Knipe DM, Golan DE, Marto JA, Coen DM. Viral mimicry of cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress. PLoS Pathogens 2009; 5: e1000275. doi:10.1371/journal.ppat.1000275.

Kamil JP, Hume AJ, Jurak I, M√ľnger K, Kalejta RF, Coen DM. Human paillomavirus 16 E7 inactivator of retinoblastoma family proteins complements human cytomegalovirus lacking UL97 protein kinase. Proc Natl Acad Sci USA 2009; 106:16823-16828.

Strang BL, Boulant S, Coen DM. Nucleolin associates with the human cytomegalovirus DNA polymerase accessory subunit UL44 and is necessary for efficient viral replication. J Virol 2010; 84:1771-1784.