Photo of Peter M. Howley,  MD

Peter M. Howley, MD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-2889
Fax: (617) 432-2882

Peter M. Howley, MD

Harvard Medical School


  • Shattuck Professor of Pathological Anatomy, Pathology, Harvard Medical School
  • Professor, Microbiology and Immunobiology, Harvard Medical School



  • Institutional Representative for HMS, Executive Committee

Research Abstract

The Howley laboratory studies the molecular biology of the papillomaviruses using the bovine papillomavirus (BPV) as well as the human papillomaviruses (HPVs). BPV is the most extensively studied of the papillomaviruses and has served as the model system for the analysis of viral transcription and of viral DNA replication. One focus of our studies has involved the viral E1 and E2 proteins and their roles in the regulation of viral transcription and DNA replication. We are conducting structure/function studies of the viral E1 and E2 proteins with the hope of developing inhibitors of their functions.

There are over 70 different HPVs, and some of them are associated with specific human cancers most notably human cervical cancer. We study the role of these HPVs in human neoplasia and the mechanisms by which these viruses contribute to cellular transformation. The virus encodes two proteins, E6 and E7, that have oncogenic properties and that contribute directly to HPV associated carcinogenesis. A particular focus of the laboratory is the study of the E6 gene, which has multiple functions, including the ability to functionally inactivate p53 by targeting its ubiquitination and proteolysis. This process is mediated by a cellular protein, E6AP, that binds to E6 and functions as a ubiquitin protein ligase in promoting the E6 dependent ubiquitination of p53. We are conducting structure/function studies on E6 and E6AP, and are studying additional functions of the papillomavirus E6 proteins. We have discovered that the BPV E6 protein binds to the cellular focal adhesion protein paxillin leading to a disruption of the actin cytoskeleton. We have also found that HPV16 E6 can bind IRF3 and inhibit its transcriptional activation function.

Publications from Harvard Catalyst Profiles

Powered by Harvard Catalyst
  • Martínez-Noël G, Szajner P, Kramer RE, Boyland KA, Sheikh A, Smith JA, Howley PM. Identification of MicroRNAs That Stabilize p53 in Human Papillomavirus-Positive Cancer Cells. J Virol 2022; 96:e0186521. PubMed
  • Martínez-Noël G, Vieira VC, Szajner P, Lilienthal EM, Kramer RE, Boyland KA, Smith JA, Howley PM. Live cell, image-based high-throughput screen to quantitate p53 stabilization and viability in human papillomavirus positive cancer cells. Virology 2021; 560:96-109. PubMed
  • Kühnle S, Martinez-Noël G, Leclere F, Hayes SD, Harper JW, Howley PM. Angelman syndrome-associated point mutations in the Zn-binding N-terminal (AZUL) domain of UBE3A ubiquitin ligase inhibit binding to the proteasome. J Biol Chem 2018. PubMed
  • Bentley P, Tan MJA, McBride AA, White EA, Howley PM. The SMC5/6 complex interacts with the papillomavirus E2 protein and influences maintenance of viral episomal DNA. J Virol 2018. PubMed
  • Martínez-Noël G, Luck K, Kühnle S, Desbuleux A, Szajner P, Galligan JT, Rodriguez D, Zheng L, Boyland K, Leclere F, Zhong Q, Hill DE, Vidal M, Howley PM. Network Analysis of UBE3A/E6AP-Associated Proteins Provides Connections to Several Distinct Cellular Processes. J Mol Biol 2018; 430:1024-1050. PubMed
  • Chiang C, Pauli EK, Biryukov J, Feister KF, Meng M, White EA, Münger K, Howley PM, Meyers C, Gack MU. The human papillomavirus E6 oncoprotein targets USP15 and TRIM25 to suppress RIG-I-mediated innate immune signaling. J Virol 2017. PubMed
  • Cheng J, Park DE, Berrios C, White EA, Arora R, Yoon R, Branigan T, Xiao T, Westerling T, Federation A, Zeid R, Strober B, Swanson SK, Florens L, Bradner JE, Brown M, Howley PM, Padi M, Washburn MP, DeCaprio JA. Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis. PLoS Pathog. 2017; 13:e1006668. PubMed
  • White EA, Münger K, Howley PM. High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation. MBio 2016. PubMed
  • Ali SM, Pal SK, Wang K, Palma NA, Sanford E, Bailey M, He J, Elvin JA, Chmielecki J, Squillace R, Dow E, Morosini D, Buell J, Yelensky R, Lipson D, Frampton GM, Howley P, Ross JS, Stephens PJ, Miller VA. Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations. Oncologist 2015. PubMed
  • Howley PM, Pfister HJ. Beta genus papillomaviruses and skin cancer. Virology 2015. PubMed
  • White EA, Kramer RE, Hwang JH, Pores Fernando AT, Naetar N, Hahn WC, Roberts TM, Schaffhausen BS, Livingston DM, Howley PM. Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 2015; 89:2857-65. PubMed
  • Galligan JT, Martinez-Noël G, Arndt V, Hayes S, Chittenden TW, Harper JW, Howley PM. Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2. J Proteome Res 2015; 14:953-66. PubMed
  • Smith JA, Haberstroh FS, White EA, Livingston DM, DeCaprio JA, Howley PM. SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter. Virology 2014; 468-470C:311-21. PubMed
  • White EA, Walther J, Javanbakht H, Howley PM. Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes. J Virol 2014. PubMed
  • French CA, Rahman S, Walsh EM, Kühnle S, Grayson AR, Lemieux ME, Grunfeld N, Rubin BP, Antonescu CR, Zhang S, Venkatramani R, Dal Cin P, Howley PM. NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. 2014. PubMed
  • Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, Lee D, Soares MA, Lambert PF, Howley PM, Harris RS. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. MBio 2014. PubMed
  • White EA, Kramer RE, Tan MJ, Hayes SD, Harper JW, Howley PM. Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity. J Virol 2012; 86:13174-86. PubMed
  • Martínez-Noël G, Galligan JT, Sowa ME, Arndt V, Overton TM, Harper JW, Howley PM. Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes. Mol Cell Biol 2012; 32:3095-106. PubMed
  • Tan MJ, White EA, Sowa ME, Harper JW, Aster JC, Howley PM. Cutaneous β-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling. Proc Natl Acad Sci U S A 2012; 109:E1473-80. PubMed
  • Powell ML, Smith JA, Sowa ME, Harper JW, Iftner T, Stubenrauch F, Howley PM. NCoR1 Mediates Papillomavirus E8;E2C Transcriptional Repression. J Virol 2010; 84:4451-60. PubMed
  • Smith JA, White EA, Sowa ME, Powell ML, Ottinger M, Harper JW, Howley PM. Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Proc Natl Acad Sci U S A 2010; 107:3752-7. PubMed
  • Fradet-Turcotte A, Brault K, Titolo S, Howley PM, Archambault J. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9. Virology 2009; 395:190-201. PubMed
  • Ottinger M, Smith JA, Schweiger MR, Robbins D, Powell ML, You J, Howley PM. Cell-type specific transcriptional activities among different papillomavirus long control regions and their regulation by E2. Virology 2009; 395:161-71. PubMed
  • You J, Li Q, Wu C, Kim J, Ottinger M, Howley PM. Regulation of aurora B expression by the bromodomain protein Brd4. Mol Cell Biol 2009; 29:5094-103. PubMed
  • Zheng G, Schweiger MR, Martinez-Noel G, Zheng L, Smith JA, Harper JW, Howley PM. Brd4 regulation of papillomavirus protein E2 stability. J Virol 2009; 83:8683-92. PubMed
  • Vos RM, Altreuter J, White EA, Howley PM. The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability. J Virol 2009; 83:8885-92. PubMed
  • Howley PM,Livingston DM. Small DNA tumor viruses: large contributors to biomedical sciences. Virology 2009; 384:256-9. PubMed
  • Mulligan P,Westbrook TF,Ottinger M,Pavlova N,Chang B,Macia E,Shi YJ,Barretina J,Liu J,Howley PM,Elledge SJ,Shi Y. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell 2008; 32:718-26. PubMed
  • Goh AM, Walters KJ, Elsasser S, Verma R, Deshaies RJ, Finley D, Howley PM. Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins. BMC Biochem 2008; 9:4. PubMed
  • DeMasi J, Chao MC, Kumar AS, Howley PM. Bovine papillomavirus E7 oncoprotein inhibits anoikis. J Virol 2007; 81:9419-25. PubMed
  • Schweiger MR, Ottinger M, You J, Howley PM. Brd4-independent transcriptional repression function of the papillomavirus e2 proteins. J Virol 2007; 81:9612-22. PubMed
  • Schweiger MR, You J, Howley PM. Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation function. J Virol 2006; 80:4276-85. PubMed