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Anamaris Colberg-Poley

Anamaris Colberg-Poley

Professor of Integrative Systems Biology
Professor of Pediatrics (Secondary)

Office Phone: 202-476-3984
Email:
Department: Integrative Systems Biology

Education

  • BS, University of Puerto Rico, 1976
  • PhD, Pennsylvania State University College of Medicine, 1980

Biography

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 graduate student in the Department of Microbiology at Penn 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 herpesvirus genes (with Lynn Enquist) and studying the cloning of the first mouse homeo box developmental genes and their transcription and regulation (with Peter Gruss). In 1986, I established my own research group in DuPont and moved the lab to Children’s in 1992.  We focused our research upon immediate early (IE) genes because of their critical role in dictating the outcome of HCMV infection whether lytic or latent. 

We learned that its HCMV UL37 proteins dually localize during lytic infection in the endoplasmic reticulum (ER) and mitochondria.  Unlike known cellular proteins that dually localize to these compartments, HCMV UL37 proteins traffic sequentially from the ER through one of its sub-domains, known as the mitochondria-associated membranes (MAM), and to mitochondria. UL37 proteins provide 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, for coordinating mitochondrial innate immune signaling and modulating mitochondrial mediated apoptosis.

We are developing new directions for the lab by studying more biologically relevant models of HCMV pathogenesis in the central nervous system. We have established the culture of human neural precursor cells (hNPCs) in low oxygen tensions and their infection with HCMV. We are undertaking characterization of HCMV genomes in the human tissues using next generation sequencing.  

The long term goals of our studies: (1) to understand the movement 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.

The new comprehensive cytomegalovirus book spanning both basic research and clinically relevant studies will be published this year (click here).

Additional Education

National Institutes of Health, Post-doc, 1980-1983, Molecular Virology
Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, FRG, Post-doc, 1983-1986, Mouse development

Bibliography

  • 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.
     
  • Colberg-Poley, A.M., Patel, M.B., Erezo, D.P.P., and Slater, J.E.  Human cytomegalovirus immediate early regulatory proteins traffic through the secretory apparatus and to mitochondria.  J. Gen. Virol. 2000; 81:1779-1789.
     
  • 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.

Research

Human cytomegalovirus (HCMV) is a medically significant human herpesvirus. HCMV congenital infection is the leading viral cause of congenital birth defects in developed countries. As UL37 proteins are anti-apoptotic and play necessary roles during HCMV growth and contribute to its pathogenesis in humans, understanding of UL37 protein trafficking and functions may provide novel targets for rational design of anti-HCMV treatments.

Trafficking of HCMV UL37 proteins 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.  To that end, we determined their targeting signals and movement to different organelles using sub-cellular fractionation and confocal microscopy. Interestingly, UL37 proteins traffic sequentially from the endoplasmic reticulum (ER) to mitochondria.  This is an understudied protein trafficking pathway in the cell.  We found that UL37 proteins traffic into the mitochondria associated membrane (MAM) fraction, a sub-ER domain that connects the ER with mitochondria. 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, UL37 protein trafficking provides an experimentally tractable tool to gain novel insight into this poorly-understood cellular trafficking pathway. 
We found that UL37 protein targeting signals to the MAM and mitochondria are dominant over those of cellular secretory and mitochondrial proteins. We are undertaking, in collaboration with Dr. Jyoti Jaiswal, the examination of UL37 protein translocation from the MAM to the outer mitochondrial membrane. We recently found that UL37 protein localizes to internal lipid rafts within the MAM in a cholesterol dependent manner.  In collaboration with Drs. Yetrib Hathout and Kristy Brown, we are examining the HCMV induced alteration of cellular proteome in the MAM and lipid rafts using quantitative proteomic analyses. 

Understanding HCMV neuropathogenesis. 

Human cytomegalovirus (HCMV) is a medically significant human herpesvirus. HCMV congenital infection is the leading viral cause of birth defects in developed countries. Particularly devastating defects are disorders of the central nervous system (CNS), including mental retardation, sensorineural hearing loss, blindness, and microencephaly.
 The goals of our studies are to understand the neuropathogenic effects of HCMV infection in physiologically relevant neural precursor cells. Because of its devastating effects on brain development, key to our understanding is the characterization of HCMV effects on human neural precursor cells (hNPCs). Until recently, these studies have been severely hindered because of its strict host species specificity and the lack of suitable models, which fully recapitulate HCMV in vivo infections. With the isolation and growth of human NPCs from post-mortem biopsies, these studies are now feasible. We are examining the effects of HCMV infection on the growth, migration and survival of hNPCs under low oxygen conditions that mimic physiological levels and favor the growth of neural stem cells. 

Systems Biology Approaches

 We have become interested in the association of HCMV infection with malignant gliomas and are undertaking, in collaboration with Drs. Eric Hoffman and Joe Devaney, the characterization of HCMV genomes present in human brain specimens using next generation sequencing.

Publications

View publications by this faculty member from January 1, 2013 - present

Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.