James M. Pipas

  • Herbert W. and Grace Boyer Chair in Molecular Biology, Professor
  • Virus Discovery and Metagenomics, Viral tumorigenesis.

Contact

Office: (412) 624-4691
Lab: (412) 624-4691
570 Crawford Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Virus Discovery and Functional Viral Metagenomics

Our laboratory uses viral proteins to uncover and explore cellular regulatory pathways. All viruses encode gene products that function in evading or suppressing host antiviral defense systems or in altering the cellular environment to make it more conducive for infection. These products act by directly associating with cellular targets, usually proteins that are components of signaling pathways, and redirecting or altering their functions. We are developing computational methods that facilitate the identification of proteins from a broad array of viruses that target cellular systems. The panviral proteome currently consists of over 600,000 virus-encoded proteins and is growing rapidly. These viral proteins serve as a highly selective toolbox for identifying and studying regulatory circuits that govern key cellular processes such as proliferation, death, metabolism, and immunity. The ultimate goal is to harness these proteins and use them to explore cellular systems important for viral infection.

Searching NGS databases for novel viruses. Thousands of specimens encompassing tissues, organisms, and metagenomes are being subjected to next generation sequencing (NGS) and the resulting data placed in databases. In addition to sequences of the target species these databases also contain sequences of microbes and viruses present in the specimen. We have developed powerful new computational tools for detecting viruses in sequence databases. We are applying these tools to search for known and novel viruses in human microbiome, environmental metagenomic, and The Cancer Genome Atlas (TCGA) databases.

Developing high throughput microfluidics for virus discovery. The inability to isolate rare viral nucleic acids from complex samples such as raw sewage or human tissues is a major obstacle to virus discovery. We have been working with Dr. David Weitz and colleagues (Applied Physics, Harvard) to develop high throughput droplet-based microfluidics for virus isolation. Microfluidics enables the production of millions of small “test tubes” that can be screened by immunoassay or PCR at remarkable speeds. Currently we are optimizing the sequencing of single viral nucleic acids from droplets.

Surveilling viruses in the environment: Project Premonition. Project Premonition is a large multi-institutional collaboration spearheaded by Microsoft Research (MSR). The Premonition team consists of computer scientists and engineers at MSR and scientists and engineers at a number of academic institutions. Our role in the project is to sequence mosquito genomes and detect viruses and other pathogens they harbor and to work with MSR to develop new software for pathogen detection.

The goal of Premonition is to detect pathogens in the environment and track their movement across different geographies and between different host species. The strategy is to use mosquitoes as a device to capture blood samples from many different vertebrate species (rodents, wild and domestic animals, and humans). Mosquitoes will be captured and subjected to NGS. In collaboration with MSR, we are developing a novel computational pipeline that simultaneously identifies: (a) the species of mosquito; (b) the species of animal from which the mosquito obtained its last blood meal; and, (c) viral, bacterial, and parasitic agents present in the mosquito or its blood meal.

 

Role of Viral Proteins in Infection and Cancer

One of the major goals of virology is to determine how each viral protein contributes to viral infection and pathology. In many cases disease results from the destruction of tissue by infection itself, or from the consequences of immune action in response to the infection. In other cases, pathology is the unintended consequence of an infection gone wrong. Such is the case in many virus-associated cancers. Currently we are focused on learning the mechanisms by which polyomaviruses and papillomaviruses manipulate cellular pathways, and how these actions contribute to cancer.

Characterizing New Jersey Polyomavirus (NJPyV) and Human Polyomavirus 9 (HuPyV9). Recently, in collaboration with Dr. Ian Lipkin at Columbia University, we have described a new polyomavirus, NJPyV, isolated from a pancreatic transplant patient. In addition, we have been studying HuPyV9, a relatively uncharacterized human polyomavirus. Like all polyomaviruses, NJPyV and HuPyV9 encode a collection of proteins called T antigens. However, the T antigens from the new viruses have a number of unique characteristics that distinguish them from previously studied T antigens. We are studying how their T antigens alter cell biology.

Exploring BKV infection with single cell transcriptomics. BKV is a human polyomavirus that is an important pathogen of kidney transplant patients. BKV establishes lifelong persistent infections in humans and most cases are harmless. However, in individuals that are immunosuppressed, such as transplant patients, the virus can undergo a rampant infection that destroys their kidneys. We are examining the effects of BKV on the global gene expression patterns of infected cells. To accomplish this we are using a newly developed strategy that merges droplet microfluidics with single cell transcriptomics. This work is in collaboration with the laboratory of Dr. David Weitz (Harvard, Applied Physics).

Determining how Human papillomavirus (HPV) contributes to head and neck cancers (HNSCC). Approximately 20% of HNSCC contain HPV and there is strong evidence indicating that the virus directly contributes to tumorigenesis in this subset of cancers. In many tumors the HPV genome is integrated in the chromosomes of the tumor thus ensuring that every time a tumor cell divides the viral genome is transmitted to both daughter cells. We have developed computational methods for mapping these integration sites and assessing their effect on gene structure and expression. We have also examined global patterns of tumor gene expression and correlated them with viral gene expression.

E-mail Lab

Starrett, G. J., C. Marcelus, P. G. Cantalupo,

Starrett, G. J., C. Marcelus, P. G. Cantalupo, J. P. Katz, J. Cheng, K. Akagi, M. Thakuria, G. Rabinowits, L. C. Wang, D. E. Symer, J. M. Pipas, R. S. Harris, and J. A. DeCaprio. 2017. Merkel cell polyomavirus exhibits dominant control of the tumor genome and transcriptome in virus-associated Merkel cell carcinoma. mBio e8(1): e02079-16. PMID: 28049147. 

Kent, L. N., J. B. Rakijas, S. K. Pandit, B. We

Kent, L. N., J. B. Rakijas, S. K. Pandit, B. Westendorp, H. Z. Chen, J. T. Huntington, X. Tang, S. Bae, A. Srivastava, S. Senapati, C. Koivisto, C. K. Martin, M. C. Cuitino, M. Perez, J. M. Clouse, V. Chokshi, N. Shinde, R. Kladney, D. Sun, A. Perez-Castro, R. B. Matondo, S. Nantasanti, M. Mokry, K. Huang, R. Machiraju, S. Fernandez, T. J. Rosol, V. Coppola, K. S. Pohar, J. M. Pipas, C. R. Schmidt, A. de Bruin, and G. Leone. 2016. E2F8 mediates tumor suppression in postnatal liver development. J. Clin. Invest. 126: 2955-2969. PMID: 27454291

Buck, C. B., K. Van Doorslaer,, A. Peretti, E.

Buck, C. B., K. Van Doorslaer,, A. Peretti, E. M. Geoghegan, M. J. Tisza, P. An, J. P. Katz, J. M. Pipas, A. A. McBride, A. C. Camus, A. J. McDermott, J. A. Dill, E. Delwart, T. F. Ng, K. Farkas, C. Austin, S. Kraberger, W. Davison, D. V. Pastrana, and A. Varsani. 2016. The ancient evolutionary history of polyomaviruses. PLoS Pathogens 12: e1005574. PMID: 27093155

Tang, X., H. Liu, A. Srivastava, T. Pecot, Z. C

Tang, X., H. Liu, A. Srivastava, T. Pecot, Z. Chen, Q. Wang, K. Huang, M. T. Saenz-Robles, P. Cantalupo, J. Pipas, and G. Leone. 2016. Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice. Sci. Data 3: 160008. PMID: 26881867

Gupta, T. M. T. Saenz-Robles, R. M. Schowalter, C.

Gupta, T. M. T. Saenz-Robles, R. M. Schowalter, C. B. Buck, and J. M. Pipas. 2015. Expression of the small T antigen of Lymphotropic Papovavirus is sufficient to transform primary mouse embryo fibroblasts. Virology 487: 112-120. PMID: 26517398

Han, H. S., P. G. Cantalupo, A. Rotem, S. K. Cockr

Han, H. S., P. G. Cantalupo, A. Rotem, S. K. Cockrell, M. Carbonnaux, J. M. Pipas, and D. A. Weitz. 2015. Whole-genome sequencing of a single viral species from a highly heterogeneous sample. Angew Chem. 54: 13985-13988. PMID: 26316088

Tao, Y., A. Rotem, H. Zhang, C. B. Chang, A. Basu,

Tao, Y., A. Rotem, H. Zhang, C. B. Chang, A. Basu, A. O. Kolawole, S. A. Koehler, Y. Ren, J. S. Lin, J. M. Pipas, A. B. Feldman, C. E. Wobus, and D. A. Weitz. 2015. Rapid targeted and culture-free viral infectivity assay in drop-based microfluidics. Lab on a Chip. 15: 3934-3940. PMID: 26304791

Tao, Y., A. Rotem, H. Zhang, S. K. Cockrell, S.

Tao, Y., A. Rotem, H. Zhang, S. K. Cockrell, S. Koehler, C. B. Chang, L. W. Ung, P. Cantalupo, Y. Ren, J. S. Lin, A. B. Feldman, C. E. Wobus, J. M. Pipas, and D. Weitz. 2015. Artifact-free quantification and sequencing of rare recombinant viruses using drop-based microfluidics. Chembiochem. 16: 2167-2171. PMID: 26247541

Liu, H., X. Tang, A. Srivastava, T. Pecot, P. Dani

Liu, H., X. Tang, A. Srivastava, T. Pecot, P. Daniel, B. Hemmelgarn, S. Reyes, N. Fackler, A. Bajwa, R. Kladney, C. Kovisto, Z. Chen, Q. Wang, K. Huang, R. Machiraju, M. T. Saenz-Robles, P. Cantalupo, J. M. Pipas, and G. Leone. 2015. Redeployment of myc and E2F1-3 drives Rb-deficient cell cycles. Nat. Cell Biol. 17: 1036-1048. PMID: 26192440. PMC4526313.

Zhang, H., S. K. Cockrell, A. O. Kolawole, A. Rote

Zhang, H., S. K. Cockrell, A. O. Kolawole, A. Rotem, A. W. Serohijos, C. B. Chang, Y. Tao, T. S. Mehoke, Y. Han, J. S. Lin, N. S. Giacobbi, A. B. Feldman, E. Shakhnovich, D. A. Weitz, C. E. Wobus, and J. M. Pipas. 2015. Isolation and analysis of rare norovirus recombinants from coinfected mice using drop-based microfluidics. J. Virol. 89: 7722-7734. PMID: 25972549

An, P., J. L. Brodsky, and J. M. Pipas. 2015. The

An, P., J. L. Brodsky, and J. M. Pipas. 2015. The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens. Arch. Biochem. & Biophys., 573: 23-31. PMID: 25752954

Gupta, T., M. T. Saenz-Robles, and J. M. Pipas.

Gupta, T., M. T. Saenz-Robles, and J. M. Pipas. 2015. Cellular transformation of mouse embryo fibroblasts in the absence of activator E2Fs. J. Virol., 89: 5124-5133. PMID: 25717106. PMC4403490.

Cantalupo, P. G., J. P. Katz, and J. M. Pipas. 201

Cantalupo, P. G., J. P. Katz, and J. M. Pipas. 2015. HeLa nucleic acid contamination in The Cancer Genome Atlas leads to the misidentification of HPV18. J. Virol., 89: 4051-4057. PMID: 25631090

Giacobbi, N. S., T. Gupta, A. T. Coxon, and J. M.

Giacobbi, N. S., T. Gupta, A. T. Coxon, and J. M. Pipas. 2015. Polyomavirus T antigens activate an antiviral state. Virology 476: 377-385. PMID: 25589241 PMC4323618

Katz, J. P., and J. M. Pipas. 2014. SummonChime

Katz, J. P., and J. M. Pipas. 2014. SummonChimera infers integrated viral genomes with nucleotide precision from NGS data. BMC_Bioformatics 15: 348-. PMID: 25331652 PMCID: PMC4210586

Ireland, A. W., T. A. Gobillot, T. Gupta, S. P. Se

Ireland, A. W., T. A. Gobillot, T. Gupta, S. P. Seguin, M. Liang, L. Resnick, M. T. Goldberg, A. Manos-Turvey, J. M. Pipas, P. Wipf, and J. L. Brodsky. 2014. Synthesis and structure-activity relationships of small molecule inhibitors of the simian virus 40 T antigen oncoprotein, an anti-polyomaviral target. Bioorganic & Medicinal Chemistry 22: 6490-6502. PMID: 25440730 PMC4293281

Seneca, N. T. M., M. T. Saenz-Robles, and J. M. Pi

Seneca, N. T. M., M. T. Saenz-Robles, and J. M. Pipas. 2014. Removal of a small C-terminal region of JCV and SV40 large T antigens has differential effects on transformation. Virology, 468-470: 47-56. PMID: 25129438 PMC4253650

Saenz-Robles, M. T., J.-L. Chong, C. Koivisto, A

Saenz-Robles, M. T., J.-L. Chong, C. Koivisto, A. Trimboli, H. Liu, G. Leone, and J. M. Pipas. 2014. Viral oncogene expression in the stem/progenitor cell compartment of the mouse intestine induces adenomatous polyps. Molecular Cancer Research 10: 1355-1364. PMID: 24994749 PMC4201981

Yu, X., X. Bian, A. Throop, L. Song, L. D. Mora

Yu, X., X. Bian, A. Throop, L. Song, L. D. Moral, J. Park, C. Seiler, M. Fiacco, J. Steel, P. Hunter, J. Saul, J. Wang, J. Qiu, J. M. Pipas, and J. LaBaer. 2014. Exploration of Panviral Proteome: High-throughput cloning and functional implications in virus-host interactions. Theranostics 4: 808-822. PMID: 24955142 PMCID: PMC4063979

Mishra, N., M. Pereira, R. H. Rhodes, P. An, J.

Mishra, N., M. Pereira, R. H. Rhodes, P. An, J. M. Pipas, K. Jain, A. Kapoor, T. Briese, P. L. Faust, and W. Ian Lipkin. 2014. Identification of a novel polyomavirus in a pancreatic transplant recipient with retinal blindness and vasculitic myopathy. J. Infect. Dis. 210: 1595-1599. PMID: 24795478 PMC4334791

Forero, A., N. S. Giacobbi, K. D. McCormick, O.

Forero, A., N. S. Giacobbi, K. D. McCormick, O. V. Gjoerup, C. J. Bakkenist, J. M. Pipas, and S. N. Sarkar. 2014. SV40 large T antigen induces ISGs through ATR kinase. J. Immunol. 192: 5933-5942. PMID: 24799566 PMC4078001

Cecchini, M. J., M. Thwaites, S. Talluri, J. I.

Cecchini, M. J., M. Thwaites, S. Talluri, J. I. MacDonald, J.-L. Chong, P. Cantalupo, P. Stafford, M. T. Saenz-Robles, S. M. Francis, D. T. Passos, J. M. Pipas, G. Leone, I. Welch, and F. A. Dick. 2014. A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene targeted mice. Mol. Cell. Biol. 34: 2017-2028. PMID: 24662053 PMCID: PMC4019062

Kolawole, A. O., M. Li, C. Xia, A. E. Fischer,

Kolawole, A. O., M. Li, C. Xia, A. E. Fischer, N. S. Giacobbi, C. M. Rippinger, J. B. G. Proescher, S. K. Wu, S. L. Bessling, M. Gamez, C. Yu, R. Zhang, T. S. Mehoke, J. M. Pipas, J. T. Wolfe, J. S. Lin, A. B. Feldman, T. J. Smith, and C. E. Wobus. 2014. Flexibility in surface exposed loops in the virus capsid mediates escape from antibody neutralization. J. Virol., 88: 4543-4557. PMID: 24501415

Williams CK, Vaithiyalingam S, Hammel M, Pipas

Williams CK, Vaithiyalingam S, Hammel M, Pipas J, Chazin WJ. Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen. Arch Biochem Biophys. 2012 Feb 15;518(2):111-8. Epub 2011 Dec 29. PMID: 22227098; PMCID: PMC3279518

Sáenz Robles MT, Case A, Chong JL, Leone G, Pip

Sáenz Robles MT, Case A, Chong JL, Leone G, Pipas JM. The retinoblastoma tumor suppressor regulates a xenobiotic detoxification pathway. PLoS One. 2011;6(10):e26019. Epub 2011 Oct 12. PMID: 22022495; PMCID: PMC3192141

Cantalupo, P.G., B. Calgua, G. Zhao, A. Hundesa

Cantalupo, P.G., B. Calgua, G. Zhao, A. Hundesa, A.D. Wier, J.P. Katz, M. Grabe, R.W. Hendrix, R. Girones, D. Wang, and J.M. Pipas. (2011) Raw sewage harbors diverse viral populations. mBio 2: e00180-11

Wenzel, P.L., J.L. Chong, M.T. Saenz-Robles, A. Ferrey, J.P. Hagan, Y.M. Gomez, R. Rajmohan, N. S

Wenzel, P.L., J.L. Chong, M.T. Saenz-Robles, A. Ferrey, J.P. Hagan, Y.M. Gomez, R. Rajmohan, N. Sharma, H.Z. Chen, J.M. Pipas, M.L. Robinson, and G. Leone (2010) Cell proliferation in the absence of E2F1-3. Dev. Biol. :

Rathi, A.V., P.G. Cantalupo, S.N. Sarkar, and J.M. Pipas (2010) Induction of interferon-stimulate

Rathi, A.V., P.G. Cantalupo, S.N. Sarkar, and J.M. Pipas (2010) Induction of interferon-stimulated genes by Simian virus 40 T antigens. Virology 406:202-211

Chong, J.L., P.L. Wenzel, M.T. Saenz-Robles, V. Nair, A. Ferrey, J.P. Hagan, Y.M. Gomez, N. Sharm

Chong, J.L., P.L. Wenzel, M.T. Saenz-Robles, V. Nair, A. Ferrey, J.P. Hagan, Y.M. Gomez, N. Sharma, H.Z. Chen, M. Ouseph, S.H. Wang, P. Trikha, B. Culp, L. Mezache, D.J. Winton, O.J. Sansom, D. Chen, R. Bremner, P.G. Cantalupo, M.L. Robinson, J.M. Pipas, and G. Leone (2009) E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells. Nature 462:930-934

Loh, J., G. Zhao, R.M. Presti, L.R. Holtz, S.R. Finkbeiner, L. Droit, Z. Villasana, C. Todd, J.M.

Loh, J., G. Zhao, R.M. Presti, L.R. Holtz, S.R. Finkbeiner, L. Droit, Z. Villasana, C. Todd, J.M. Pipas, B. Calgua, R. Girones, D. Wang, and H.W. Virgin (2009) Detection of novel sequences related to african Swine Fever virus in human serum and sewage. J Virol 83:13019-13025

Rathi, A.V., M.T. Saenz Robles, P.G. Cantalupo, R.H. Whitehead, and J.M. Pipas (2009) Simian viru

Rathi, A.V., M.T. Saenz Robles, P.G. Cantalupo, R.H. Whitehead, and J.M. Pipas (2009) Simian virus 40 T-antigen-mediated gene regulation in enterocytes is controlled primarily by the Rb-E2F pathway. J Virol 83:9521-9531

Ahuja, D., A.V. Rathi, A.E. Greer, X.S. Chen, and J.M. Pipas (2009) A structure-guided mutational

Ahuja, D., A.V. Rathi, A.E. Greer, X.S. Chen, and J.M. Pipas (2009) A structure-guided mutational analysis of simian virus 40 large T antigen: identification of surface residues required for viral replication and transformation. J Virol 83:8781-8788

Holtz, L.R., S.R. Finkbeiner, G. Zhao, C.D. Kirkwood, R. Girones, J.M. Pipas, and D. Wang (2009)

Holtz, L.R., S.R. Finkbeiner, G. Zhao, C.D. Kirkwood, R. Girones, J.M. Pipas, and D. Wang (2009) Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread. Virol J 6:8686

Saenz Robles, M.T., and J.M. Pipas (2009) T antigen transgenic mouse models. Semin Cancer Bio

Saenz Robles, M.T., and J.M. Pipas (2009) T antigen transgenic mouse models. Semin Cancer Biol 19:229-235

Pipas, J.M. (2009) SV40: Cell transformation and tumorigenesis. Virology 384

Pipas, J.M. (2009) SV40: Cell transformation and tumorigenesis. Virology 384:294-303

Wright, C.M., S.P. Seguin, S.W. Fewell, H. Zhang, C. Ishwad, A. Vats, C.A. Lingwood, P. Wipf, E.

Wright, C.M., S.P. Seguin, S.W. Fewell, H. Zhang, C. Ishwad, A. Vats, C.A. Lingwood, P. Wipf, E. Fanning, J.M. Pipas, and J.L. Brodsky (2009) Inhibition of Simian Virus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen. Virus Res. 0:

Cantalupo, P.G., M.T. Saenz-Robles, A.V. Rathi, R.W. Beerman, W.H. Patterson, R.H. Whitehead, and

Cantalupo, P.G., M.T. Saenz-Robles, A.V. Rathi, R.W. Beerman, W.H. Patterson, R.H. Whitehead, and J.M. Pipas (2009) Cell-type specific regulation of gene expression by simian virus 40 T antigens. Virology 0:

Wright, C.M., R.J. Chovatiya, N.E. Jameson, D.M. Turner, G. Zhu, S. Werner, D.M. Huryn, J.M. Pipa

Wright, C.M., R.J. Chovatiya, N.E. Jameson, D.M. Turner, G. Zhu, S. Werner, D.M. Huryn, J.M. Pipas, B.W. Day, P. Wipf, and J.L. Brodsky (2008) Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg. Med. Chem. 16:3291-3301

Zhao, X., R.J. Madden-Fuentes, B.X. Lou, J.M. Pipas, J. Gerhardt, C.J. Rigell, and E. Fanning (20

Zhao, X., R.J. Madden-Fuentes, B.X. Lou, J.M. Pipas, J. Gerhardt, C.J. Rigell, and E. Fanning (2008) Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells. J. Virol. 82:5316-5328

Saenz-Robles, M.T., J.A. Markovics, J.L. Chong, R. Opavsky, R.H. Whitehead, G. Leone, and J.M. Pi

Saenz-Robles, M.T., J.A. Markovics, J.L. Chong, R. Opavsky, R.H. Whitehead, G. Leone, and J.M. Pipas (2007) Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. J. Virol. 81:13191-13199
Dr. Pipas received his Ph.D. in 1975 with Robert Reeves at Florida State University, performed postdoctoral studies with John Wilson at Baylor College and with Dan Nathans at the Johns Hopkins School of Medicine, and joined the Department in 1980.