Scott S. Terhune, PhD
Postdoctoral Fellow, Proteomics/Cytomegalovirus Biology, Princeton University, 2007
- Antiviral Agents
- Cell Cycle
- Cyclin-Dependent Kinase Inhibitor p21
- Histone Acetyltransferases
- Histone Deacetylases
- Host-Pathogen Interactions
- Protein Kinases
- Signal Transduction
- STAT3 Transcription Factor
- Tumor Suppressor Protein p53
Methodologies and Techniques
- Cell Cycle
- DNA, Viral
- Drug Synergism
- Protein Interaction Mapping
- RNA, Viral
- Virus Replication
- Dept Representative, Faculty Council
- Past Chair, Faculty Career Development Committee
- Program Representative, IDP Executive Evaluation Committee
- Vice Chair, Institutional Biosafety Committee
Our research focuses on determining the molecular functions of human cytomegalovirus (HCMV) proteins during infection and disease. HCMV is a member of the beta-herpesvirus family of viruses which includes HHV-6 and 7. Infection occurs upon exposure to virus-containing body fluids, is life-long and generally asymptomatic in healthy children and adults. However, during pregnancy, HCMV infection may result in congenital birth defects including hearing loss and neurological damage. In immunologically immature or compromised children and adults, infection often results in life threatening diseases. And, increasing evidence suggestions that persistent life-long HCMV infection is associated with numerous chronic diseases including atherosclerosis, immuno-senescence, cancer and possibly Alzheimer’s Disease.
Research projects in the lab focus on defining how HCMV manipulate cellular processes and networks to construct an environment that supports virus replication. A long-term goal is to identify potential therapeutic approaches to manage infections. Students and staff in the lab develop hypothesis-driven projects that integrate traditional methods in virology with advanced technologies. We use approaches in viral genetics and molecular and cellular biology with varying applications in proteomics (e.g. phospho-proteomics, MALDI-imaging, SILAC quantification), computational modeling of protein networks, and hiPSC-derived multicellular and functional tissue types (e.g. connective tissues, neural organoids, hematopoietic cells). We collaborate with MCW faculty and other international experts in several of these areas. In addition, we often incorporate our observations and new approaches into MCW graduate education.
Over the years, we have defined the molecular functions for numerous HCMV proteins during infection. This body of research has revealed interconnected and dynamic networks between viral proteins and host proteins and processes. As an example, early collaborative studies on HCMV pUL38 revealed interactions with cellular TSC2 resulting in constitutive mTORC1 activity. Those studies revealed that pUL38 also binds to HCMV pUL29/28 and cellular HDAC1 deacetylase. Subsequently, our research demonstrated that HDAC1 binds to the pUL97 kinase while pUL29/28 binds to the transcription factor, p53 and a chromatin remodeling complex referred to as NuRD. Each of these interactions results in functional consequences to cellular processes including alterations in gene expression, apoptosis and/or cell cycle. We have uncovered additional interactions and networks not mentioned in this summary. Cumulatively, our work has revealed the complexity of network dysregulation created by HCMV proteins and required to support productive infection. By collaborating with investigators in other disciplines, we are currently extending these and other projects by using multicellular functional tissues and capturing network complexity and dynamics using computational modeling.
(Sison SL, O'Brien BS, Johnson AJ, Seminary ER, Terhune SS, Ebert AD.) J Virol. 2019 Sep 01;93(17).
(Rak MA, Buehler J, Zeltzer S, Reitsma J, Molina B, Terhune S, Goodrum F.) J Virol. 2018 10 15;92(20).
(Forte E, Swaminathan S, Schroeder MW, Kim JY, Terhune SS, Hummel M.) MBio. 2018 09 11;9(5).
(Kriegel AJ, Terhune SS, Greene AS, Noon KR, Pereckas MS, Liang M.) J Biol Chem. 2018 09 07;293(36):14080-14088.
(Armstrong RM, Carter DC, Atkinson SN, Terhune SS, Zahrt TC.) J Bacteriol. 2018 08 15;200(16).
(Westdorp KN, Terhune SS.) Antiviral Res. 2018 05;153:33-38.
(Mounce BC, Mboko WP, Bigley TM, Terhune SS, Tarakanova VL.) J Virol. 2018 01 01;92(1).
(Gonyo P, Bergom C, Brandt AC, Tsaih SW, Sun Y, Bigley TM, Lorimer EL, Terhune SS, Rui H, Flister MJ, Long RM, Williams CL.) Oncogene. 2017 12 14;36(50):6873-6883.
(Westdorp KN, Sand A, Moorman NJ, Terhune SS.) J Virol. 2017 09 15;91(18).
(Greseth MD, Carter DC, Terhune SS, Traktman P.) Mol Cell Proteomics. 2017 04;16(4 suppl 1):S124-S143.
(Buehler J, Zeltzer S, Reitsma J, Petrucelli A, Umashankar M, Rak M, Zagallo P, Schroeder J, Terhune S, Goodrum F.) PLoS Pathog. 2016 05;12(5):e1005655.
(Bigley TM, McGivern JV, Ebert AD, Terhune SS.) Antiviral Res. 2016 May;129:67-73.