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Adjunct Professor of Genomics and Precision Medicine
Adjunct Professor of Pediatrics (Secondary)
Office Phone: 202-476-6029
Department: Genomics and Precision Medicine
- BS, University of Puerto Rico, 1976
- PhD, Pennsylvania State University College of Medicine, 1980
My research group studies human cytomegalovirus (HCMV) infection to understand how it takes over its host cells. During my undergraduate training in Puerto Rico, I developed a keen interest in viruses and decided to pursue graduate studies in the US. I trained as a doctoral student in the Department of Microbiology and Immunology at the Pennsylvania State University College of Medicine (Hershey) because of its strong emphasis on virology. My post-doctoral fellowships expanded my training to include the then-emergent field of recombinant DNA technology using bacteriophage cloning of human herpesvirus genomes (with Lynn Enquist) and cloning of the first mouse homeo box developmental genes and studying their transcription and regulation during differentiation and mouse development (with Peter Gruss). In 1986, I established my own research group in E.I. DuPont Central Research & Development in Wilmington, Delaware.
In 1992, I moved the lab to Children’s National in Washington DC. We focused our research upon HCMV immediate early (IE) genes because of their critical role in dictating the outcome of viral infection, that is, whether HCMV infection becomes permissive or latent.
We learned that its HCMV UL37 immediate early proteins including vMIA dually localize during lytic infection in the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM). Unlike known cellular proteins that dually localize to these compartments, HCMV vMIA protein traffics sequentially from the ER through one of its sub-domains, known as the mitochondria-associated membranes (MAM), and to mitochondria. vMIA provides us with valuable tools to decipher this unconventional protein trafficking pathway and why HCMV specifically targets the MAM. The MAM is becoming increasingly recognized as providing critical sites for sensing of ER stress, ER calcium signaling to mitochondria, coordinating mitochondrial innate immune signaling and modulating mitochondrial mediated apoptosis.
The long term goals of our studies: (1) to understand the trafficking of proteins from the ER to mitochondria using HCMV proteins as a model, (2) to gain insight into the HCMV:host cell interaction and (3) to provide molecular biology resources, virology or training to other investigators.
I recently edited a new comprehensive cytomegalovirus book spanning both basic research and clinically relevant studies (click here).
- National Institutes of Health, Post-doc, 1980-1983, Molecular Virology
- Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, FRG, Post-doc, 1983-1986, Mouse development
- Colberg-Poley, A.M., Isom, H.C., and Rapp, F. Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus. Proc. Natl. Acad. Sci. USA 1979; 76: 5948-5951.
- Colberg-Poley, A.M., Voss, S.D., Chowdhury, K., and Gruss, P. Structural analysis of murine genes containing homoeo box sequences and their expression in embryonal carcinoma cells. Nature 1985; 314: 713-718.
- Colberg-Poley, A.M., Voss, S.D., Chowdhury, K., Stewart, C.L., Wagner, E.F., and Gruss, P. Clustered homeo boxes are expressed during murine development. Cell 1985; 43: 39-45.
Tenney, D.J. and Colberg-Poley, A.M. Expression of the human cytomegalovirus UL36-38 immediate early region during permissive infection. Virology 1991; 182: 199-210.
- Su, Y., Adair, R., Davis, C.N., DiFronzo, N.L., and Colberg-Poley, A.M. Convergence of RNA cis elements and cellular polyadenylation factors in the regulation of human cytomegalovirus UL37 exon 1 unspliced RNA production. J. Virol. 2003; 77:12729-12741.
- Gaddy, C.E., Wong, D.S., Markowitz-Shulman, A., and Colberg-Poley, A. M. Redistribution of the subcellular distribution of key cellular RNA-processing factors during human cytomegalovirus infection. J. Gen. Virology 2010; 91:1547-1559.
- Williamson, C.D. and Colberg-Poley, A.M. Intracellular sorting signals for sequential trafficking of human cytomegalovirus UL37 proteins to the endoplasmic reticulum and mitochondria. J. Virol. 2010; 84: 6400-6409.
- Bozidis, P., Williamson, C.D., Wong, D.S. and Colberg-Poley, A.M. Trafficking of UL37 proteins into the mitochondrion-associated membrane during permissive human cytomegalovirus infection. J. Virol. 2010; 84:7898-7903.
Williamson, C.D., Zhang, A., and Colberg-Poley, A.M. The human cytomegalovirus UL37 exon 1 protein associates with internal lipid rafts. J. Virol. 2011; 85:2100–2111.
Zhang, A., Williamson, C.D., Wong, D.S., Bullough, M.D., Brown, K.J., Hathout, Y., and Colberg-Poley, A.M. Quantitative proteomic analyses of human cytomegalovirus-induced restructuring of endoplasmic reticulum-mitochondrial contacts at late times of permissive infection. Molecular and Cellular Proteomics 2011; 10:M111.009936.
Zhang, A., Hildreth, R.L., and Colberg-Poley, A.M. Cytomegalovirus inhibits apoptosis by proteasomal degradation of Bax at ER-mitochondrial contacts. Journal of Virology 2013; 87:5657-5668. Selected for JVI Spotlights
Bhuvanendran, S.,, Salka, K. , Rainey, K., Sreetama, S.C., Williams, E., Leeker, M., Prasad, V., Boyd, J., Patterson, G.H., Jaiswal, J.K., and Colberg-Poley, A.M. Superresolution imaging of human cytomegalovirus vMIA localization in sub-mitochondrial compartments. Viruses 2014; 6:1612-1636.
Williamson, C.D., Wong, D.S., Bozidis, P., Zhang, A., and Colberg-Poley, A.M. 2015. Isolation of Endoplasmic Reticulum, Mitochondria, and Mitochondria-Associated Membrane and Detergent Resistant Membrane Fractions from Transfected Cells and from Human Cytomegalovirus-Infected Primary Fibroblasts. Current Protocols in Cell Biology 2015; 68:3.27.1-3.27.33.
Complete List of Published Work in MyBibliography:
Human cytomegalovirus (HCMV) is a medically significant human herpesvirus. Congenital HCMV infection is the leading viral cause of birth defects in developed countries and HCMV is a significant pathogen in immunodeficient patients. As UL37 proteins, including vMIA, are anti-apoptotic and extend the viability of infected cells, thereby enhancing production of progeny virus and contribute to its pathogenesis in humans. Thus, understanding of vMIA protein trafficking and functions may provide novel targets for rational design of anti-HCMV treatments.
Trafficking of HCMV vMIA protein from the endoplasmic reticulum to mitochondria.
The goals of our studies are to identify the mechanistic basis of the trafficking of the HCMV UL37 anti-apoptotic protein, known as vMIA. To that end, we determined its targeting signals and movement to different organelles using sub-cellular fractionation and confocal microscopy. Interestingly, vMIA traffics sequentially from the endoplasmic reticulum (ER) to the outer mitochondrial membrane (OMM). This is an understudied protein trafficking pathway in the cell.
We further found that vMIA traffics into the mitochondria associated membrane (MAM) fraction, a sub-ER domain at which ER and OMM are closely apposed. The MAM is increasingly recognized as providing sites for coordination of ER stress responses, regulating calcium signaling to mitochondria, modulating mitochondrial-mediated apoptosis and mitochondria innate immune signaling. Since only a few cellular mitochondrial proteins are known to originate in the ER, HCMV vMIA protein trafficking provides an experimentally tractable tool to gain novel insight into this poorly-understood cellular trafficking pathway. These studies provide insight into the viral protein signals mediating its ER to mitochondrial protein trafficking. Importantly, multiple cellular proteins were subsequently found to traffic analogously from the ER to the OMM.
In collaboration with Drs. Yetrib Hathout and Kristy Brown (Children's Research Institute), we performed the first quantitative mass spectrometry determination of the human mitochondria associated membrane (MAM) proteome. For these experiments, we adapted and further developed the use of Percoll gradients to obtain highly purified MAM and mitochondrial fractions. We published detailed protocols for purification of the MAM and mitochondria in the Current Protocols of Cell Biology series. The MAM proteomic analysis contributed to our understanding of the composition of the MAM of normal human fibroblasts, which was poorly characterized at the time, and how pathogens change its composition.
In collaboration with Drs. Jyoti Jaiswal (Children's Research Institute) and George Patterson (NIH), we have undertaken the use of superresolution imaging of viral proteins in the MAM and mitochondria. We were the first to use high resolution and superresolution microscopy to examine the sub-mitochondrial location of the HCMV vMIA protein. Importantly, we found clustering of the viral protein at the OMM, similar to mitochondrial proteins, including VDAC, TOM, and MINOS.
2013-2016 National Science Foundation (MCB-1244509)
Using a viral protein to study the functional organization of ER-mitochondrial membrane contacts and trafficking across this compartment
B.S. Biology, University of Puerto Rico at Mayaguez, magna cum laude
Charles Darwin Award (Biology Department), University of Puerto Rico at Mayagüez
Faculty of Arts and Science Award, University of Puerto Rico at Mayagüez
University award, Luis Stefani Raffucci Award, University of Puerto Rico at Mayagüez
Ford Foundation Graduate Fellowship
Sigma Xi, full member
Sigma Xi Annual Research Award, Pennsylvania State University Chapter
Post Doctoral Fellowship, National Research Service, NIH
Alexander von Humboldt Fellowship, Germany
Career Investigator Award, American Lung Association
Editorial Board, Journal of Virology
Editorial Board, TOVJ, The Open Virology Journal
Humboldtian on Campus for CRI, Alexander von Humboldt Foundation
First Annual Mentorship Award, Translational Science Mentorship Excellence, 10th Annual Children’s National Medical Center Research Day, CNMC
Guest Editor for Special Issue of Viruses, Recent CMV Research (online and printed book)
Editorial Board, Viruses
Director and Lecturer, BMSC 8210, Genes to Cells, Lectures: Mitochondria, Cell Cycle, and Apoptosis, and paper discussions
Director, BMSC 8234, Biochemistry & Systems Biology Seminar Series
Lecturer, 2nd year Medical Students, Microbiology/Infectious Diseases: Immunohematology, Inflammation and Infection, Introduction to Viruses – Classification, Structure, Replication and Pathogenesis
Lecturer, 1st year Medical Students, Microbiology/Infections Diseases, I-3, Introduction to Viruses – Classification, Structure, Replication and Pathogenesis
Lecturer, MICR 8210, Infection and Immunity, Introduction to Viruses and Herpesviruses
Director, BMSC 8216, Scientific Writing
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.