Frederic D. Bushman, PhD

Frederic D. Bushman, PhD

Frederic D. Bushman, PhD, is a professor of microbiology at the University of Pennsylvania. He is also an academic investigator in childhood obesity research at The Children's Hospital of Philadelphia.

Locations: Main Campus
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Education and Training

Fellowship

Molecular Biology - Harvard University, Boston, MA Molecular Biology - National Institutes of Health, Bethesda, MD

Undergraduate Degree

BA in Biology & English - Amherst College, Amherst, MA

Graduate Degree

PhD in Cell & Developmental Biology - Harvard University, Boston, MA

Titles and Academic Titles

Professor of Microbiology, University of Pennsylvania

Academic Investigator, Healthy Weight Program

Research Interests

Human microbiome
Human gene therapy
HIV Poxviruses
DNA modifying enzymes
Lateral DNA transfer

Publications

Papers

2014

Osborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth MR, Tomov VT, Kobuley D, Tran SV, Bittinger K, Bailey AG, Laughlin AL, Boucher JL, Wherry EJ, Bushman FD, Allen JE, Virgin HW, Artis D. Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science. 2014 Aug 1;345(6196):578-82. doi: 10.1126/science.1256942. Epub 2014 Jul 17.

Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J, Laughlin A, Grunberg S, Baldassano RN, Lewis JD, Li H, Thom SR, Bushman FD, Vinogradov SA, Wu GD. Correlation Between Intraluminal Oxygen Gradient and Radial Partitioning of Intestinal Microbiota. Gastroenterology. 2014 Jul 18. pii: S0016-5085(14)00916-0. doi: 10.1053/j.gastro.2014.07.020.

Margolis D, Bushman F. HIV/AIDS. Persistence by proliferation? Science. 2014 Jul 11;345(6193):143-4. doi: 10.1126/science.1257426.

Kiem HP, Baum C, Bushman FD, Byrne BJ, Carter BJ, Cavagnaro J, Malech HL, Mendell JR, Naldini LM, Sorrentino BP, Williams DA, Flotte TR. Charting a clear path: the ASGCT Standardized Pathways Conference. Mol Ther. 2014 Jul;22(7):1235-8. doi: 10.1038/mt.2014.95.

Gupta K, Brady T, Dyer BM, Malani N, Hwang Y, Male F, Nolte RT, Wang L, Velthuisen E, Jeffrey J, Van Duyne GD, Bushman FD. Allosteric Inhibition of Human Immunodeficiency Virus Integrase: LATE BLOCK DURING VIRAL REPLICATION AND ABNORMAL MULTIMERIZATION INVOLVING SPECIFIC PROTEIN DOMAINS. J Biol Chem. 2014 Jul 25;289(30):20477-20488. Epub 2014 Jun 5.

Sharma A, Slaughter A, Jena N, Feng L, Kessl JJ, Fadel HJ, Malani N, Male F, Wu L, Poeschla E, Bushman FD, Fuchs JR, Kvaratskhelia M. A new class of multimerization selective inhibitors of HIV-1 integrase. PLoS Pathog. 2014 May 29;10(5):e1004171. doi: 10.1371/journal.ppat.1004171. eCollection 2014 May.

Bushman FD. Engineering the human genome: reflections on the beginning. Hum Gene Ther. 2014 May;25(5):395-400. doi: 10.1089/hum.2014.2524.

Manganaro L, Pache L, Herrmann T, Marlett J, Hwang Y, Murry J, Miorin L, Ting AT, König R, García-Sastre A, Bushman FD, Chanda SK, Young JA, Fernandez-Sesma A, Simon V. Tumor suppressor cylindromatosis (CYLD) controls HIV transcription in an NF-κB-dependent manner. J Virol. 2014 Jul;88(13):7528-40. doi: 10.1128/JVI.00239-14. Epub 2014 Apr 23.

Aiyer S, Swapna GV, Malani N, Aramini JM, Schneider WM, Plumb MR, Ghanem M, Larue RC, Sharma A, Studamire B, Kvaratskhelia M, Bushman FD, Montelione GT, Roth MJ. Altering murine leukemia virus integration through disruption of the integrase and BET protein family interaction. Nucleic Acids Res. 2014;42(9):5917-28. doi: 10.1093/nar/gku175. Epub 2014 Mar 12.

Larue RC, Plumb MR, Crowe BL, Shkriabai N, Sharma A, DiFiore J, Malani N, Aiyer SS, Roth MJ, Bushman FD, Foster MP, Kvaratskhelia M. Bimodal high-affinity association of Brd4 with murine leukemia virus integrase and mononucleosomes. Nucleic Acids Res. 2014 Apr;42(8):4868-81. doi: 10.1093/nar/gku135. Epub 2014 Feb 11.

Petersen J, Drake MJ, Bruce EA, Riblett AM, Didigu CA, Wilen CB, Malani N, Male F, Lee FH, Bushman FD, Cherry S, Doms RW, Bates P, Briley K Jr. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog. 2014 Feb 6;10(2):e1003911. doi: 10.1371/journal.ppat.1003911. eCollection 2014 Feb.

Berry CC, Ocwieja KE, Malani N, Bushman FD. Comparing DNA integration site clusters with scan statistics. Bioinformatics. 2014 Jun 1;30(11):1493-500. doi: 10.1093/bioinformatics/btu035. Epub 2014 Jan 30.

Korn LL, Thomas HL, Hubbeling HG, Spencer SP, Sinha R, Simkins HM, Salzman NH, Bushman FD, Laufer TM. Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells. Mucosal Immunol. 2014 Sep;7(5):1045-57. doi: 10.1038/mi.2013.121. Epub 2014 Jan 22.

2013

Alenghat T, Osborne LC, Saenz SA, Kobuley D, Ziegler CG, Mullican SE, Choi I, Grunberg S, Sinha R, Wynosky-Dolfi M, Snyder A, Giacomin PR, Joyce KL, Hoang TB, Bewtra M, Brodsky IE, Sonnenberg GF, Bushman FD, Won KJ, Lazar MA, Artis D. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature. 2013 Dec 5;504(7478):153-7. doi: 10.1038/nature12687. Epub 2013 Nov 3.

De Rijck J, de Kogel C, Demeulemeester J, Vets S, El Ashkar S, Malani N, Bushman FD, Landuyt B, Husson SJ, Busschots K, Gijsbers R, Debyser Z. The BET family of proteins targets moloney murine leukemia virus integration near transcription start sites. Cell Rep. 2013 Nov 27;5(4):886-94. doi: 10.1016/j.celrep.2013.09.040. Epub 2013 Oct 31.

Bushman FD, Lewis JD, Wu GD. Diet, gut enterotypes and health: is there a link? Nestle Nutr Inst Workshop Ser. 2013;77:65-73. doi: 10.1159/000351385. Epub 2013 Aug 29. Review.

Liu C, Mauk M, Gross R, Bushman FD, Edelstein PH, Collman RG, Bau HH. Membrane-based, sedimentation-assisted plasma separator for point-of-care applications. Anal Chem. 2013 Nov 5;85(21):10463-70. doi: 10.1021/ac402459h. Epub 2013 Oct 25.

Dollive S, Chen YY, Grunberg S, Bittinger K, Hoffmann C, Vandivier L, Cuff C, Lewis JD, Wu GD, Bushman FD. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLoS One. 2013 Aug 19;8(8):e71806. doi: 10.1371/journal.pone.0071806. eCollection 2013.

Sherrill-Mix S, Lewinski MK, Famiglietti M, Bosque A, Malani N, Ocwieja KE, Berry CC, Looney D, Shan L, Agosto LM, Pace MJ, Siliciano RF, O'Doherty U, Guatelli J, Planelles V, Bushman FD. HIV latency and integration site placement in five cell-based models. Retrovirology. 2013 Aug 16;10:90. doi: 10.1186/1742-4690-10-90.

Minot S, Bryson A, Chehoud C, Wu GD, Lewis JD, Bushman FD. Rapid evolution of the human gut virome. Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12450-5. doi: 10.1073/pnas.1300833110. Epub 2013 Jul 8.

Sharma A, Larue RC, Plumb MR, Malani N, Male F, Slaughter A, Kessl JJ, Shkriabai N, Coward E, Aiyer SS, Green PL, Wu L, Roth MJ, Bushman FD, Kvaratskhelia M. BET proteins promote efficient murine leukemia virus integration at transcription start sites. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12036-41. doi: 10.1073/pnas.1307157110. Epub 2013 Jul 1.

Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, Wu GD, Lewis JD, Bushman FD. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One. 2013 Jun 17;8(6):e66019. doi: 10.1371/journal.pone.0066019. Print 2013.

Han D, Walsh MC, Cejas PJ, Dang NN, Kim YF, Kim J, Charrier-Hisamuddin L, Chau L, Zhang Q, Bittinger K, Bushman FD, Turka LA, Shen H, Reizis B, Defranco AL, Wu GD, Choi Y. Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance. Immunity. 2013 Jun 27;38(6):1211-22. doi: 10.1016/j.immuni.2013.05.012. Epub 2013 Jun 20.

Li X, Burnight ER, Cooney AL, Malani N, Brady T, Sander JD, Staber J, Wheelan SJ, Joung JK, McCray PB Jr, Bushman FD, Sinn PL, Craig NL. piggyBac transposase tools for genome engineering. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):E2279-87. doi: 10.1073/pnas.1305987110. Epub 2013 May 30.

Bushman FD, Barton S, Bailey A, Greig C, Malani N, Bandyopadhyay S, Young J, Chanda S, Krogan N. Bringing it all together: big data and HIV research. AIDS. 2013 Mar 13;27(5):835-8. doi: 10.1097/QAD.0b013e32835cb785.

Hepworth MR, Monticelli LA, Fung TC, Ziegler CG, Grunberg S, Sinha R, Mantegazza AR, Ma HL, Crawford A, Angelosanto JM, Wherry EJ, Koni PA, Bushman FD, Elson CO, Eberl G, Artis D, Sonnenberg GF. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 2013 Jun 6;498(7452):113-7. doi: 10.1038/nature12240. Epub 2013 May 22.

Wojcechowskyj JA, Didigu CA, Lee JY, Parrish NF, Sinha R, Hahn BH, Bushman FD, Jensen ST, Seeholzer SH, Doms RW. Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry. Cell Host Microbe. 2013 May 15;13(5):613-23. doi: 10.1016/j.chom.2013.04.011.

Schneider WM, Brzezinski JD, Aiyer S, Malani N, Gyuricza M, Bushman FD, Roth MJ. Viral DNA tethering domains complement replication-defective mutations in the p12 protein of MuLV Gag. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9487-92. doi: 10.1073/pnas.1221736110. Epub 2013 May 9.

Zhong L, Malani N, Li M, Brady T, Xie J, Bell P, Li S, Jones H, Wilson JM, Flotte TR, Bushman FD, Gao G. Recombinant adeno-associated virus integration sites in murine liver after ornithine transcarbamylase gene correction. Hum Gene Ther. 2013 May;24(5):520-5. doi: 10.1089/hum.2012.112.

Sundararaman SA, Liu W, Keele BF, Learn GH, Bittinger K, Mouacha F, Ahuka-Mundeke S, Manske M, Sherrill-Mix S, Li Y, Malenke JA, Delaporte E, Laurent C, Mpoudi Ngole E, Kwiatkowski DP, Shaw GM, Rayner JC, Peeters M, Sharp PM, Bushman FD, Hahn BH. Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7020-5. doi: 10.1073/pnas.1305201110. Epub 2013 Apr 8.

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.

Vets S, De Rijck J, Brendel C, Grez M, Bushman F, Debyser Z, Gijsbers R. Transient Expression of an LEDGF/p75 Chimera Retargets Lentivector Integration and Functionally Rescues in a Model for X-CGD. Mol Ther Nucleic Acids. 2013 Mar 5;2:e77. doi: 10.1038/mtna.2013.4.

Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES, Sodergren E, Mitreva M, Abubucker S, Martin J, Yao G, Campbell TB, Flores SC, Ackerman G, Stombaugh J, Ursell L, Beck JM, Curtis JL, Young VB, Lynch SV, Huang L, Weinstock GM, Knox KS, Twigg H, Morris A, Ghedin E, Bushman FD, Collman RG, Knight R, Fontenot AP; Lung HIV Microbiome Project. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med. 2013 May 15;187(10):1110-7. doi: 10.1164/rccm.201211-2145OC.

Brady T, Kelly BJ, Male F, Roth S, Bailey A, Malani N, Gijsbers R, O'Doherty U, Bushman FD. Quantitation of HIV DNA integration: effects of differential integration site distributions on Alu-PCR assays. J Virol Methods. 2013 Apr;189(1):53-7. doi: 10.1016/j.jviromet.2013.01.004. Epub 2013 Jan 21.

Tebas P, Stein D, Binder-Scholl G, Mukherjee R, Brady T, Rebello T, Humeau L, Kalos M, Papasavvas E, Montaner LJ, Schullery D, Shaheen F, Brennan AL, Zheng Z, Cotte J, Slepushkin V, Veloso E, Mackley A, Hwang WT, Aberra F, Zhan J, Boyer J, Collman RG, Bushman FD, Levine BL, June CH. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV. Blood. 2013 Feb 28;121(9):1524-33. doi: 10.1182/blood-2012-07-447250. Epub 2012 Dec 20. Erratum in: Blood. 2014 Jul 24;124(4):663.

2012

Woodard LE, Li X, Malani N, Kaja A, Hice RH, Atkinson PW, Bushman FD, Craig NL, Wilson MH. Comparative analysis of the recently discovered hAT transposon TcBuster in human cells. PLoS One. 2012;7(11):e42666. doi: 10.1371/journal.pone.0042666. Epub 2012 Nov 15.

Li X, Ewis H, Hice RH, Malani N, Parker N, Zhou L, Feschotte C, Bushman FD, Atkinson PW, Craig NL. A resurrected mammalian hAT transposable element and a closely related insect element are highly active in human cell culture. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E478-87. doi: 10.1073/pnas.1121543109. Epub 2012 Oct 22.

Chen J, Bushman FD, Lewis JD, Wu GD, Li H. Structure-constrained sparse canonical correlation analysis with an application to microbiome data analysis. Biostatistics. 2013 Apr;14(2):244-58. doi: 10.1093/biostatistics/kxs038. Epub 2012 Oct 15. PLoS One. 2012;7(10):e46966. doi: 10.1371/journal.pone.0046966. Epub 2012 Oct 10.

Peterfreund GL, Vandivier LE, Sinha R, Marozsan AJ, Olson WC, Zhu J, Bushman FD. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile. Schrijvers R, Vets S, De Rijck J, Malani N, Bushman FD, Debyser Z, Gijsbers R. HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells. Retrovirology. 2012 Oct 9;9:84. doi: 10.1186/1742-4690-9-84.

Gupta K, Curtis JE, Krueger S, Hwang Y, Cherepanov P, Bushman FD, Van Duyne GD. Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA. Structure. 2012 Nov 7;20(11):1918-28. doi: 10.1016/j.str.2012.08.023. Epub 2012 Sep 20.

Charlson ES, Bittinger K, Chen J, Diamond JM, Li H, Collman RG, Bushman FD. Assessing bacterial populations in the lung by replicate analysis of samples from the upper and lower respiratory tracts. PLoS One. 2012;7(9):e42786. doi: 10.1371/journal.pone.0042786. Epub 2012 Sep 6.

Ocwieja KE, Sherrill-Mix S, Mukherjee R, Custers-Allen R, David P, Brown M, Wang S, Link DR, Olson J, Travers K, Schadt E, Bushman FD. Dynamic regulation of HIV-1 mRNA populations analyzed by single-molecule enrichment and long-read sequencing. Nucleic Acids Res. 2012 Nov 1;40(20):10345-55. doi: 10.1093/nar/gks753. Epub 2012 Aug 25.

Pace MJ, Graf EH, Agosto LM, Mexas AM, Male F, Brady T, Bushman FD, O'Doherty U. Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 2012;8(7):e1002818. doi: 10.1371/journal.ppat.1002818. Epub 2012 Jul 26.

Minot S, Wu GD, Lewis JD, Bushman FD. Conservation of gene cassettes among diverse viruses of the human gut. PLoS One. 2012;7(8):e42342. doi: 10.1371/journal.pone.0042342. Epub 2012 Aug 10.

Charlson ES, Diamond JM, Bittinger K, Fitzgerald AS, Yadav A, Haas AR, Bushman FD, Collman RG. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am J Respir Crit Care Med. 2012 Sep 15;186(6):536-45. doi: 10.1164/rccm.201204-0693OC. Epub 2012 Jul 12. 

Dollive S, Peterfreund GL, Sherrill-Mix S, Bittinger K, Sinha R, Hoffmann C, Nabel CS, Hill DA, Artis D, Bachman MA, Custers-Allen R, Grunberg S, Wu GD, Lewis JD, Bushman FD. A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples. Genome Biol. 2012 Jul 3;13(7):R60. doi: 10.1186/gb-2012-13-7-r60.

Chen J, Bittinger K, Charlson ES, Hoffmann C, Lewis J, Wu GD, Collman RG, Bushman FD, Li H. Associating microbiome composition with environmental covariates using generalized UniFrac distances. Bioinformatics. 2012 Aug 15;28(16):2106-13. doi: 10.1093/bioinformatics/bts342. Epub 2012 Jun 17.

Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA, Kunisawa J, Shibata N, Grunberg S, Sinha R, Zahm AM, Tardif MR, Sathaliyawala T, Kubota M, Farber DL, Collman RG, Shaked A, Fouser LA, Weiner DB, Tessier PA, Friedman JR, Kiyono H, Bushman FD, Chang KM, Artis D. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science. 2012 Jun 8;336(6086):1321-5. doi: 10.1126/science.1222551. Epub 2012 Jun 6.

Corrigan-Curay J, Cohen-Haguenauer O, O'Reilly M, Ross SR, Fan H, Rosenberg N, Somia N, King N, Friedmann T, Dunbar C, Aiuti A, Naldini L, Baum C, von Kalle C, Kiem HP, Montini E, Bushman F, Sorrentino BP, Carrondo M, Malech H, Gahrton G, Shapiro R, Wolff L, Rosenthal E, Jambou R, Zaia J, Kohn DB. Challenges in vector and trial design using retroviral vectors for long-term gene correction in hematopoietic stem cell gene therapy. Mol Ther. 2012 Jun;20(6):1084-94. doi: 10.1038/mt.2012.93.

Culyba M, Hwang Y, Attar S, Madrid PB, Bupp J, Huryn D, Sanchez L, Grobler J, Miller MD, Bushman FD. Bulged DNA substrates for identifying poxvirus resolvase inhibitors. Nucleic Acids Res. 2012 Sep;40(16):e124. doi: 10.1093/nar/gks325. Epub 2012 May 11.

Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G, Hege KM, Vogel AN, Kalos M, Riley JL, Deeks SG, Mitsuyasu RT, Bernstein WB, Aronson NE, Levine BL, Bushman FD, June CH. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med. 2012 May 2;4(132):132ra53. doi: 10.1126/scitranslmed.3003761.

Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, Larosa DF, Renner ED, Orange JS, Bushman FD, Artis D. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med. 2012 Mar 25;18(4):538-46. doi: 10.1038/nm.2657.

Schrijvers R, De Rijck J, Demeulemeester J, Adachi N, Vets S, Ronen K, Christ F, Bushman FD, Debyser Z, Gijsbers R. LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs. PLoS Pathog. 2012;8(3):e1002558. doi: 10.1371/journal.ppat.1002558. Epub 2012 Mar 1.

Lehman DA, Wamalwa DC, McCoy CO, Matsen FA, Langat A, Chohan BH, Benki-Nugent S, Custers-Allen R, Bushman FD, John-Stewart GC, Overbaugh J. Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment. J Acquir Immune Defic Syndr. 2012 Jul 1;60(3):225-33. doi: 10.1097/QAI.0b013e3182515730.

Minot S, Grunberg S, Wu GD, Lewis JD, Bushman FD. Hypervariable loci in the human gut virome. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3962-6. doi: 10.1073/pnas.1119061109. Epub 2012 Feb 21.

Mei J, Liu Y, Dai N, Hoffmann C, Hudock KM, Zhang P, Guttentag SH, Kolls JK, Oliver PM, Bushman FD, Worthen GS. Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice. J Clin Invest. 2012 Mar 1;122(3):974-86. doi: 10.1172/JCI60588. Epub 2012 Feb 13.

Berry CC, Gillet NA, Melamed A, Gormley N, Bangham CR, Bushman FD. Estimating abundances of retroviral insertion sites from DNA fragment length data. Bioinformatics. 2012 Mar 15;28(6):755-62. doi: 10.1093/bioinformatics/bts004. Epub 2012 Jan 11.