Graduate Group in Genomics and Computational Biology

Frederic D. Bushman, Ph.D.

faculty photo
Professor of Microbiology
Department: Microbiology

Contact information
426 Johnson Pavilion
Department of Microbiology
3610 Hamilton Walk
Philadelphia, PA 19104-6076
Office: (215) 573-8732
Fax: (215) 573-4856
B.A. (Biology and English)
Amherst College, 1980.
Ph.D. (Cellular and Developmental Biology)
Harvard University, 1988.
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Description of Research Expertise

Research Interests
Human microbiome, human gene therapy HIV, Poxviruses, DNA modifying enzymes, Lateral DNA transfer.

Key words: microbiome, gene therapy, HIV, integration, integrase, poxvirus, DNA modifying enzyme, virology, variola, resolvase.

Description of Research
Research in the Bushman laboratory focuses on host-microbe interactions in health and disease, with particular focus on studies of 1) the human microbiome, 2) HIV pathogenesis, and 3) DNA integration in human gene therapy.

In recent years, our work has been driven increasingly by the remarkable new deep sequencing methods, which can produce more than 100 billion bases of DNA sequence information in a single instrument run.

For microbiome studies, this allows comprehensive analysis of microbial populations without reliance on culture-based methods, which can detect only a small fraction of all organisms present.

For studies of HIV replication, this allows analysis of complex viral populations or distributions of retroviral DNA integration sites in the human genome.

For gene therapy, this allows tracking of integrated vectors in gene-corrected subjects and molecular characterization of adverse events.

Sample acquisition can sometimes be difficult in such projects, but bioinformatic analysis afterwards is almost always harder. We have been carrying out this type of study since 2002, when we showed that HIV DNA integration in human cells was favored in active transcription units, and over the years have built up partially automated software pipelines that allow efficient analysis deep sequencing data.

Lab members and collaborators cover a range of specialties, including clinical researchers, molecular biologists, computational biologists, and statisticians.

Rotation Projects
Rotation projects center on the human microbiome in health and disease, analysis of viral replication, and studies of integration in human gene therapy.

Lab personnel:

Staff Scientists
Young Hwang

Post-doctoral Researchers
Jacque Young

Graduate Students
Alexandra Bryson
Christel Chehoud
Erik Clarke
Scott Sherrill-Mix
Sesh Sundararaman

Research Specialists
Christian Hoffmann
Alice Laughlin
Frances Male
Eric Sherman

Aubrey Bailey
Kyle Bittinger
Nirav Malani

Administrative Coordinator
Laurie Zimmerman

Selected Publications

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, Sesma AF, Simon V.: Tumor suppressor cylindromatosis (CYLD) controls HIV transcription in a NF-κB dependent manner. J. Virol. [Epub ahead of print], 2014.

Ravel J, Blaser MJ, Braun J, Bushman FD, Chang EB, Julian DE, Dewey KG, Timothy D, Dominguez-Bello M, Erdman SE, Brett FB, Garrett WS, Huffnagle GB, Huttenhower C, Jansson J, Jeffrey IB, Jobin C, Khoruts A, Kong HH, Lampe JW, Ley RE, Littman DR, Mazmanian SK, Mills DA, Neish AS, Petrof E, Relman DA, Rhodes R Turnbaugh PJ, Young VB, Knight R, White O, Brown E. : Human microbiome science: Vision for the future. Submitted 2014.

Ciuffi A, Bushman FD: Integration. Encyclopedia of AIDS Submitted, 2014.

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: Linking inhibition of late replication steps by an allosteric inhibitor of human immunodeficiency virus integrase with multimerization of specific protein domains. J. Biol. Chem. submitted, 2014.

Kelly BJ, Gross R, Lewis JD, Collman RG, Li H, Bushman FD: Power and sample size estimation for microbiome studies using UniFrac and PERMANOVA. Submitted 2014.

Albenberg L, Esipova TV, Judge C, Bittinger K, Chen J, Grunberg S, Baldassano R, Lewis JD, Li H, Bushman FD, Vinogradov SA, Wu GD: Radial oxygen gradient correlates with partitioning of the luminal gut microbiota. Submitted 2014.

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. (Epub ahead of print), 2014.

Berry CC, Ocwieja KE, Malani N, Bushman FD: Comparing DNA integration site clusters with scan statistics. Bioinformatics (Epub ahead of print), 2014.

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. 10: e1003911, 2014.

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. (Epub ahead of print), 2014.

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Last updated: 05/22/2014
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