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Department of

Molecular Genetics, Biochemistry & Microbiology

Photo of  William Miller, PhD

William Miller, PhD

Professor of Molecular Genetics and Director of the Molecular Genetics Graduate Program

Education/Credentials
  • B.S.: Penn State University
  • Ph.D.: University of North Carolina
  • Post Doc: Duke University School of Medicine
  • Graduate Fellow: University of Cincinnati

Research/Clinical Interests

The Miller laboratory is interested in the mechanisms by which viral pathogens manipulate host cell signal transduction pathways. We are primarily using cytomegaloviruses to examine how the pathogens alter signaling pathways directed by G-protein coupled receptors (GPCRs) to facilitate robust replication in tissues important for host-host dissemination.

Contact Information
  • 2206 Medical Sciences Building
  • 231 Albert Sabin Way
  • Cincinnati, Ohio 45267
  • Office 513-558-0866
  • Fax 513-558-5604
  • Email william.miller@uc.edu

Peer Reviewed Publications

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Krishna, Benjamin A; Humby, Monica S; Miller, William E; O'Connor, Christine M 2019. Human cytomegalovirus G protein-coupled receptor US28 promotes latency by attenuating c-fos. Proceedings of the National Academy of Sciences of the United States of America, 116 5, 1755-1764

Morrison, Kristen M; Beucler, Matthew J; Campbell, Emily O; White, Margaret A; Boody, Rachel E; Wilson, Keith C; Miller, William E 2019. Development of a Primary Human Cell Model for the Study of Human Cytomegalovirus Replication and Spread within Salivary Epithelium. Journal of virology, 93 3,

Krishna, Benjamin A; Miller, William E; O'Connor, Christine M 2018. US28: HCMV's Swiss Army Knife. Viruses, 10 8,

K. Brown, A. Filuta, M-G. Ludwig, K. Seuwen, J. Jaros, S. Vidal, K. Arora, A. Naren, K. Kandasamy, K. Parthasarathi, S. Offermanns, R. Mason, W.E. Miller, J.A. Whitsett, J. Bridges 2017. Epithelial Adgrf5 (Gpr116) Regulates Pulmonary Alveolar Homeostasis via Gq/11 Signaling JCI Insight, 2 11, 1-11

Dogra, Pranay; Miller-Kittrell, Mindy; Pitt, Elisabeth; Jackson, Joseph W; Masi, Tom; Copeland, Courtney; Wu, Shuen; Miller, William E; Sparer, Tim 2016. A little cooperation helps murine cytomegalovirus (MCMV) go a long way: MCMV co-infection rescues a chemokine salivary gland defect. The Journal of general virology, 97 11, 2957-2972

Low, Hann; Mukhamedova, Nigora; Cui, Huanhuan L; McSharry, Brian P; Avdic, Selmir; Hoang, Anh; Ditiatkovski, Michael; Liu, Yingying; Fu, Ying; Meikle, Peter J; Blomberg, Martin; Polyzos, Konstantinos A; Miller, William E; Religa, Piotr; Bukrinsky, Michael; Soderberg-Naucler, Cecilia; Slobedman, Barry; Sviridov, Dmitri 2016. Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells. Cell Reports, 16 1, 186-200

Wu, Shu-En; Miller, William E 2016. The HCMV US28 vGPCR induces potent Galphaq/PLeta signaling in monocytes leading to increased adhesion to endothelial cells Virology, 497 , 233-243

Wu, Shu-En; Miller, William E 2015. The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line Virology, 483 , 83-95

Bittencourt, Fabiola M; Wu, Shu-En; Bridges, James P; Miller, William E 2014. The M33 G protein-coupled receptor encoded by murine cytomegalovirus is dispensable for hematogenous dissemination but is required for growth within the salivary gland Journal of virology, 88 20, 11811-24

O'Connor, C. M. and Miller, W. E. 2014. Methods for Studying the Function of Cytomegalovirus GPCRs Methods in Molecular Biology: Human Cytomegaloviruses, 1119 , 133-64

Luttrell, Louis M; Miller, William E 2013. Arrestins as regulators of kinases and phosphatases Progress in molecular biology and translational science, 118 , 115-47

Millen, Scott H; Schneider, Olivia D; Miller, William E; Monaco, John J; Weiss, Alison A 2013. Pertussis toxin B-pentamer mediates intercellular transfer of membrane proteins and lipids. PloS one, 8 9, e72885

Simard, Elie; Kovacs, Jeffrey J; Miller, William E; Kim, Jihee; Grandbois, Michel; Lefkowitz, Robert J 2013. Beta-Arrestin regulation of myosin light chain phosphorylation promotes AT1aR-mediated cell contraction and migration. PloS one, 8 11, e80532

Miller, William E; Zagorski, William A; Brenneman, Joanna D; Avery, Diana; Miller, Jeanette L C; O 2012. US28 is a potent activator of phospholipase C during HCMV infection of clinically relevant target cells. PloS one, 7 11, e50524

Schneider, Olivia D; Millen, Scott H; Weiss, Alison A; Miller, William E 2012. Mechanistic insight into pertussis toxin and lectin signaling using T cells engineered to express a CD8alpha/CD3zeta chimeric receptor Biochemistry, 51 20, 4126-37

Swope, Viki B; Jameson, Joshua A; McFarland, Kevin L; Supp, Dorothy M; Miller, William E; McGraw, Dennis W; Patel, Mira A; Nix, Matthew A; Millhauser, Glenn L; Babcock, George F; Abdel-Malek, Zalfa A 2012. Defining MC1R regulation in human melanocytes by its agonist alpha-melanocortin and antagonists agouti signaling protein and beta-defensin 3 The Journal of investigative dermatology, 132 9, 2255-62

Schneider, Olivia D; Weiss, Alison A; Miller, William E 2009. Pertussis toxin signals through the TCR to initiate cross-desensitization of the chemokine receptor CXCR4. Journal of immunology (Baltimore, Md. : 1950), 182 9, 5730-9

Shenoy, Sudha K; Modi, Aalok S; Shukla, Arun K; Xiao, Kunhong; Berthouze, Magali; Ahn, Seungkirl; Wilkinson, Keith D; Miller, William E; Lefkowitz, Robert J 2009. Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2. Proceedings of the National Academy of Sciences of the United States of America, 106 16, 6650-5

Sherrill, Joseph D; Stropes, Melissa P; Schneider, Olivia D; Koch, Diana E; Bittencourt, Fabiola M; Miller, Jeanette L C; Miller, William E 2009. Activation of intracellular signaling pathways by the murine cytomegalovirus G protein-coupled receptor M33 occurs via PLC-beta/PKC-dependent and -independent mechanisms Journal of virology, 83 16, 8141-52

Stropes, Melissa P; Schneider, Olivia D; Zagorski, William A; Miller, Jeanette L C; Miller, William E 2009. The carboxy-terminal tail of human cytomegalovirus (HCMV) US28 regulates both chemokine-independent and chemokine-dependent signaling in HCMV-infected cells Journal of virology, 83 19, 10016-27

Sherrill, Joseph D; Miller, William E 2008. Desensitization of herpesvirus-encoded G protein-coupled receptors. Life sciences, 82 3-4, 125-34

Stropes, Melissa P M; Miller, William E 2008. Functional analysis of human cytomegalovirus pUS28 mutants in infected cells. The Journal of general virology, 89 Pt 1, 97-105

Schneider, Olivia D; Weiss, Alison A; Miller, William E 2007. Pertussis toxin utilizes proximal components of the T-cell receptor complex to initiate signal transduction events in T cells. Infection and immunity, 75 8, 4040-9

Sherrill, Joseph D; Miller, William E 2006. G protein-coupled receptor (GPCR) kinase 2 regulates agonist-independent Gq/11 signaling from the mouse cytomegalovirus GPCR M33. The Journal of biological chemistry, 281 52, 39796-805

Ardila-Osorio, Hector; Pioche-Durieu, Catherine; Puvion-Dutilleul, Francine; Clausse, Bernard; Wiels, Joëlle; Miller, William; Raab-Traub, Nancy; Busson, Pierre 2005. TRAF interactions with raft-like buoyant complexes, better than TRAF rates of degradation, differentiate signaling by CD40 and EBV latent membrane protein 1. International journal of cancer. Journal international du cancer, 113 2, 267-75

Wu, Jiao-Hui; Goswami, Robi; Kim, Luke K; Miller, William E; Peppel, Karsten; Freedman, Neil J 2005. The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism for feedback inhibition. The Journal of biological chemistry, 280 35, 31027-35

Mialet-Perez, Jeanne; Green, Stuart A; Miller, William E; Liggett, Stephen B 2004. A primate-dominant third glycosylation site of the beta2-adrenergic receptor routes receptors to degradation during agonist regulation. The Journal of biological chemistry, 279 37, 38603-7

Stropes, Melissa P M; Miller, William E 2004. Signaling and regulation of G-protein coupled receptors encoded by cytomegaloviruses. Biochemistry and cell biology = Biochimie et biologie cellulaire, 82 6, 636-42

Witherow, D Scott; Garrison, Tiffany Runyan; Miller, William E; Lefkowitz, Robert J 2004. beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proceedings of the National Academy of Sciences of the United States of America, 101 23, 8603-7

Ahn, Seungkirl; Nelson, Christopher D; Garrison, Tiffany Runyan; Miller, William E; Lefkowitz, Robert J 2003. Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference. Proceedings of the National Academy of Sciences of the United States of America, 100 4, 1740-4

Chen, Wei; ten Berge, Derk; Brown, Jeff; Ahn, Seungkirl; Hu, Liaoyuan A; Miller, William E; Caron, Marc G; Barak, Larry S; Nusse, Roel; Lefkowitz, Robert J 2003. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science (New York, N.Y.), 301 5638, 1391-4

Miller, William E; Houtz, Daniel A; Nelson, Christopher D; Kolattukudy, P E; Lefkowitz, Robert J 2003. G-protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR. The Journal of biological chemistry, 278 24, 21663-71

Wu, Jiao-Hui; Peppel, Karsten; Nelson, Christopher D; Lin, Fang-Tsyr; Kohout, Trudy A; Miller, William E; Exum, Sabrina T; Freedman, Neil J 2003. The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor. The Journal of biological chemistry, 278 45, 44238-45

Feldman, David S; Zamah, A Musa; Pierce, Kristen L; Miller, William E; Kelly, Francine; Rapacciuolo, Antonio; Rockman, Howard A; Koch, Walter J; Luttrell, Louis M 2002. Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus. The Journal of biological chemistry, 277 32, 28631-40

Laporte, Stephane A; Miller, William E; Kim, Kyeong-Man; Caron, Marc G 2002. beta-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a beta-arrestin binging site in beta 2-adaptin. The Journal of biological chemistry, 277 11, 9247-54

Perry, Stephen J; Baillie, George S; Kohout, Trudy A; McPhee, Ian; Magiera, Maria M; Ang, Kok Long; Miller, William E; McLean, Alison J; Conti, Marco; Houslay, Miles D; Lefkowitz, Robert J 2002. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science (New York, N.Y.), 298 5594, 834-6

Chen, W; Hu, L A; Semenov, M V; Yanagawa, S; Kikuchi, A; Lefkowitz, R J; Miller, W E 2001. beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proceedings of the National Academy of Sciences of the United States of America, 98 26, 14889-94

Claing, A; Chen, W; Miller, W E; Vitale, N; Moss, J; Premont, R T; Lefkowitz, R J 2001. beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis. The Journal of biological chemistry, 276 45, 42509-13

Imamura, T; Huang, J; Dalle, S; Ugi, S; Usui, I; Luttrell, L M; Miller, W E; Lefkowitz, R J; Olefsky, J M 2001. beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport. The Journal of biological chemistry, 276 47, 43663-7

Luttrell, L M; Roudabush, F L; Choy, E W; Miller, W E; Field, M E; Pierce, K L; Lefkowitz, R J 2001. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proceedings of the National Academy of Sciences of the United States of America, 98 5, 2449-54

Miller, W E; Lefkowitz, R J 2001. Expanding roles for beta-arrestins as scaffolds and adapters in GPCR signaling and trafficking. Current opinion in cell biology, 13 2, 139-45

Miller, W E; Lefkowitz, R J 2001. Arrestins as signaling molecules involved in apoptotic pathways: a real eye opener. Science's STKE : signal transduction knowledge environment, 2001 69, pe1

Miller, W E; McDonald, P H; Cai, S F; Field, M E; Davis, R J; Lefkowitz, R J 2001. Identification of a motif in the carboxyl terminus of beta -arrestin2 responsible for activation of JNK3. The Journal of biological chemistry, 276 30, 27770-7

Hu, L A; Tang, Y; Miller, W E; Cong, M; Lau, A G; Lefkowitz, R J; Hall, R A 2000. beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors. The Journal of biological chemistry, 275 49, 38659-66

Maudsley, S; Pierce, K L; Zamah, A M; Miller, W E; Ahn, S; Daaka, Y; Lefkowitz, R J; Luttrell, L M 2000. The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor. The Journal of biological chemistry, 275 13, 9572-80

McDonald, P H; Chow, C W; Miller, W E; Laporte, S A; Field, M E; Lin, F T; Davis, R J; Lefkowitz, R J 2000. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science (New York, N.Y.), 290 5496, 1574-7

Miller, W E; Maudsley, S; Ahn, S; Khan, K D; Luttrell, L M; Lefkowitz, R J 2000. beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis. The Journal of biological chemistry, 275 15, 11312-9

Seo, B; Choy, E W; Maudsley, S; Miller, W E; Wilson, B A; Luttrell, L M 2000. Pasteurella multocida toxin stimulates mitogen-activated protein kinase via G(q/11)-dependent transactivation of the epidermal growth factor receptor. The Journal of biological chemistry, 275 3, 2239-45

Fries, K L; Miller, W E; Raab-Traub, N 1999. The A20 protein interacts with the Epstein-Barr virus latent membrane protein 1 (LMP1) and alters the LMP1/TRAF1/TRADD complex. Virology, 264 1, 159-66

Lin, F T; Miller, W E; Luttrell, L M; Lefkowitz, R J 1999. Feedback regulation of beta-arrestin1 function by extracellular signal-regulated kinases. The Journal of biological chemistry, 274 23, 15971-4

Luttrell, L M; Ferguson, S S; Daaka, Y; Miller, W E; Maudsley, S; Della Rocca, G J; Lin, F; Kawakatsu, H; Owada, K; Luttrell, D K; Caron, M G; Lefkowitz, R J 1999. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science (New York, N.Y.), 283 5402, 655-61

Miller, W E; Raab-Traub, N 1999. The EGFR as a target for viral oncoproteins. Trends in microbiology, 7 11, 453-8

Takeshita, H; Yoshizaki, T; Miller, W E; Sato, H; Furukawa, M; Pagano, J S; Raab-Traub, N 1999. Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus latent membrane protein 1 C-terminal activation regions 1 and 2. Journal of virology, 73 7, 5548-55

Tang, Y; Hu, L A; Miller, W E; Ringstad, N; Hall, R A; Pitcher, J A; DeCamilli, P; Lefkowitz, R J 1999. Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor. Proceedings of the National Academy of Sciences of the United States of America, 96 22, 12559-64

Hatzivassiliou, E; Miller, W E; Raab-Traub, N; Kieff, E; Mosialos, G 1998. A fusion of the EBV latent membrane protein-1 (LMP1) transmembrane domains to the CD40 cytoplasmic domain is similar to LMP1 in constitutive activation of epidermal growth factor receptor expression, nuclear factor-kappa B, and stress-activated protein kinase. Journal of immunology (Baltimore, Md. : 1950), 160 3, 1116-21

Miller, W E; Cheshire, J L; Baldwin, A S; Raab-Traub, N 1998. The NPC derived C15 LMP1 protein confers enhanced activation of NF-kappa B and induction of the EGFR in epithelial cells. Oncogene, 16 14, 1869-77

Miller, W E; Cheshire, J L; Raab-Traub, N 1998. Interaction of tumor necrosis factor receptor-associated factor signaling proteins with the latent membrane protein 1 PXQXT motif is essential for induction of epidermal growth factor receptor expression. Molecular and cellular biology, 18 5, 2835-44

Patel, A; Hanson, J; McLean, T I; Olgiate, J; Hilton, M; Miller, W E; Bachenheimer, S L 1998. Herpes simplex type 1 induction of persistent NF-kappa B nuclear translocation increases the efficiency of virus replication. Virology, 247 2, 212-22

Miller, W E; Mosialos, G; Kieff, E; Raab-Traub, N 1997. Epstein-Barr virus LMP1 induction of the epidermal growth factor receptor is mediated through a TRAF signaling pathway distinct from NF-kappaB activation. Journal of virology, 71 1, 586-94

Fries, K L; Miller, W E; Raab-Traub, N 1996. Epstein-Barr virus latent membrane protein 1 blocks p53-mediated apoptosis through the induction of the A20 gene. Journal of virology, 70 12, 8653-9

Miller, W E; Earp, H S; Raab-Traub, N 1995. The Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor. Journal of virology, 69 7, 4390-8

Miller, W E; Edwards, R H; Walling, D M; Raab-Traub, N 1994. Sequence variation in the Epstein-Barr virus latent membrane protein 1. The Journal of general virology, 75 ( Pt 10) , 2729-40