Philip Pellett, Ph.D., is the Chair of the Department of Microbiology, Immunology and Biochemistry for the Wayne State University School of Medicine.
Dr. Pellett joined the School of Medicine faculty in 2007. He received his bachelor’s degree in chemistry in 1980 from Ohio University and his doctoral degree in virology from the University of Chicago in 1986, working in the laboratory of Bernard Roizman, Sc.D.
He served as Chief of the Herpesvirus Section of the U.S. Centers for Disease Control and Prevention from 1986 until 2003. He directed Herpesvirus Translational and Basic Research at the Cleveland Clinic from 2003 to 2007. While in Cleveland, he served as a professor of Molecular Biology and Microbiology at Case Western Reserve University, and as a professor of Molecular Medicine for the Cleveland Clinic Lerner College of Medicine at Caser Western Reserve University.
Dr. Pellett has been an advisor and consultant to the National Institutes of Health, the U.S. Food and Drug Administration, the National Science Foundation, the director of the National Cancer Institute and the Human Herpesvirus 6 Foundation. He chaired the Herpesvirus Study Group of the Vertebrate Virus Subcommittee of the International Committee for Taxonomy of Viruses from 2006 to 2012. He is an associate editor of the Journal of Medical Virology, and serves on the editorial boards of several virology and immunology journals, including Journal of Virology. He has been invited to write numerous editorial commentaries and is responsible for chapters about herpesviruses in highly regarded reference texts, including the "Manual of Clinical Microbiology" and "Fields Virology."
Dr. Pellett's research is aimed at understanding the biology of human herpesviruses and improving clinical outcomes of herpesvirus infections. He studies how human cytomegalovirus (HCMV) remodels cells it infects, transforming them into factories that can produce an infectious virus. HCMV is the leading cause of congenitally-acquired cerebral palsy and deafness, and an important cause of mental retardation, seizures, blindness and death. One in 150 children is born with the virus, and one in 750 is born with or will develop permanent disabilities caused by congenital HCMV.
Herpesviruses: Molecular Marvels and Potent Pathogens
Of the human herpesviruses, HCMV has the greatest clinical impact. It is a leading cause of congenitally acquired mental retardation and deafness, is a major pathogen in immunocompromised patients, and may contribute to the development of atherosclerosis and other inflammation-linked vascular diseases. We are engaged in basic studies of the molecular and cellular biology of HCMV, as well as in clinically oriented translational research.
HCMV Molecular and Cellular Biology
Cell biology of HCMV virion assembly. Human cytomegalovirus induces profound changes in infected-cell morphology, including formation of large cytoplasmic inclusions that correspond to the virion assembly complex (AC). We found that the AC is arranged such that Golgi- and trans-Golgi-derived vesicles are at the outer periphery of the AC and early endosome-derived vesicles are at its center. This counterintuitive arrangement nonetheless allows for a conventional order of membrane-protein biosynthesis and transport. The resulting model of AC structure suggests a mechanism by which the virus can regulate the order of tegument assembly. We have identified three HCMV genes that are important for cVAC biogenesis and are studying their mechanisms of action.
The Translational Research component of our program has involved multidisciplinary collaboration between basic laboratory scientists, clinical virologists, immunologists, infectious disease specialists, epidemiologists, and biostatisticians. We have examined the pathogenic role of herpesviruses in immunocompromised patients, and developed numerous methods for diagnosis of herpesvirus infections.
- Goldfarb J, Borges N, Gowans LK, Kohn D, Worley S, Li L, Yen-Lieberman B, Lach D, Danziger-Isakov L, Yee-Guardino S, Trunick C, Pellett PE. 2016. Absence of human herpesvirus 6B detection in association with illness in children undergoing cancer chemotherapy. J Med Virol. doi: 10.1002/jmv.24482. [Epub ahead of print] Medline
- Pellett PE. 2015. Indictment by association: once is not enough. J Infect Dis. 212:509-12. Medline
- Das S, Ortiz DA, Gurczynski SJ, Khan F, Pellett PE. Identification of human cytomegalovirus genes important for biogenesis of the cytoplasmic virion assembly complex. J Virol. 88:9086-99, 2014. Medline
- Gurczynski SJ, Das S, Pellett PE. Deletion of the human cytomegalovirus US17 gene increases the ratio of genomes per infectious unit and alters regulation of immune and endoplasmic reticulum stress response genes at early and late times after infection. J Virol. 88:2168-82, 2014. Medline
- Pellett PE, Roizman B. 2013. The family Herpesviridae: a brief introduction, in Fields Virology, 6th ed. Knipe et al., eds. Lippincott, Williams, & Wilkins, Philadelphia. Volume 2, Chapter 59, p.1802-1822
- Hladik W, Pellett PE, Hancock J, Downing R, Gao H, Packel L, Mimbe D, Nzaro E, Mermin J. Association between transfusion with human herpesvirus 8 antibody-positive blood and subsequent mortality. J Infect Dis. 206:1497-503. 2012. Medline
- Lum LG, Ramesh M, Thakur A, Mitra S, Deol A, Uberti JP, Pellett PE. Targeting cytomegalovirus-infected cells using T cells armed with anti-CD3 anti-CMV bispecific antibody. Biol. Blood Marrow Transplant. 18:1012-22. 2012. Medline
- Pellett PE, Ablashi DV, Ambros PF, Agut H, Caserta MT, Descamps V, Flamand L, Gautheret-Dejean A, Hall CB, Kamble RT, Kuehl U, Lassner D, Lautenschlager I, Loomis KS, Luppi M, Lusso P, Medveczky PG, Montoya JG, Mori Y, Ogata M, Pritchett JC, Rogez S, Seto E, Ward KN, Yoshikawa T, Razonable RR. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol. 22:144-55. 2012. Medline
- Das, S. and P.E. Pellett. 2011. Spatial relationships between markers for secretory and endosomal machinery in human cytomegalovirus-infected cells versus those in uninfected cells. J. Virol. 85:5864-5879. Medline
- Dhuruvasan, K, G. Sivasubramanian, and P.E. Pellett. 2011. Roles of host and viral microRNAs in human cytomegalovirus biology. Virus Res. 157:180-192. Medline
- Wang, F.Z., F. Weber, C. Croce, C.-G. Liu, X. Liao, and P.E. Pellett. 2008. Human cytomegalovirus infection alters expression of cellular microRNA species that affect its replication. J. Virol. 82:9065-9074. J. Virol. Spotlight article (82:8955) and ASM Microbe Journal Highlights (3:530). Medline
- Das, S., A. Vasanji, and P.E. Pellett. 2007. Three dimensional structure of the human cytomegalovirus cytoplasmic virion assembly complex includes a reoriented secretory apparatus. J. Virol. 81:11861-11869. Medline
- Pellett, P.E. and J. Goldfarb. 2007. Multilane highway to congenital infection. J. Infect. Dis. 196:1276-1278. Medline
- Das, S. and P.E. Pellett. 2007. Members of the HCMV US12 family of predicted heptaspanning membrane proteins have unique intracellular distributions, including association with the cytoplasmic virion assembly complex. Virology 361:263-273. Medline
- Pellett, P.E. and B. Roizman. 2007. The Herpesviridae: a brief introduction. In Fields Virology, 5th ed., Knipe et al., eds., Lippincott, Williams, & Wilkins, Philadelphia, Vol. 2, Chapt. 66: 2479-2499.
- Hladik, W., S.C. Dollard, J. Mermin, A. L. Fowlkes, R. Downing, M. M. Amin, F. Banage, E. Nzaro, P. Kataaha, T.J. Dondero, P.E. Pellett, E.M. Lackritz. 2006. Transmission of human herpesvirus 8 by blood transfusion. New England J. Med., 355:1331-1338. Medline
- Lesniewski, M., S. Das, Y. Skomorovska-Prokvolit, F.-Z. Wang, and P.E. Pellett. 2006. Primate cytomegalovirus US12 gene family: a distinct and diverse clade of seven-transmembrane proteins. Virology 354:286-298.
- Das, S., Y. Skomorovska-Prokvolit, F.-Z. Wang, and P.E. Pellett. 2006. Infection-dependent nuclear localization of US17, a member of the US12 family of human cytomegalovirus-encoded seven-transmembrane proteins. J. Virol. 80:1191-1203.