Frederic D. Bushman

faculty photo
William Maul Measey Professor in Microbiology
Department: Microbiology

Contact information
426 Johnson Pavilion
Department of Microbiology
3610 Hamilton Walk
Philadelphia, PA 19104-6076
Office: (215) 573-8732
Lab: (215) 573-8733
Education:
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.

Keywords
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.

Honors, Awards, Memberships
Fellow of the American Association for the Advancement of Science, 2014
Pioneer Award, Journal of Human Gene Therapy, 2014
Fellow of the American Academy of Microbiology, 2009
Master of Arts, Honoris Causa, University of Pennsylvania, 2004
Stohlman Scholar, Leukemia and Lymphoma Society of America, 2001
Scholar, Leukemia Society of America, Inc., 1996-2001
Special Fellow, Leukemia Society of America, Inc., 1992-1995
Fellow, Leukemia Society of America, Inc., 1989-1992
Editorial Board, Virology, 2001
Editorial Board, Journal of Virology, 1995

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 Scientist
Young Hwang

Lab Manager
Aoife Doto

Post-doctoral Researchers
Scott Sherrill-Mix, PhD
Varun Aggarwala, PhD
Guanxiang Liang, PhD

Graduate Students
Arwa Abbas
Erik Clarke
Grant Eilers
Louis Taylor

Research Specialists
Audrey Allen
John Gregg
Abigail Lauder
Jacob Leiby
Shantan Reddy

Bioinformaticians
Jesse Connell
John Everett, PhD
Kevin McCormick
Chris Nobles, PhD

Executive Assistant to the Chair
Laurie Zimmerman

Description of Itmat Expertise

human microbiome, HIV, gene correction in humans

Selected Publications

Lewis JD, Chen EZ, Baldassano RN, Otley AR, Griffiths AM, Lee D, Bittinger K, Bailey A, Friedman ES, Hoffmann C, Albenberg L, Sinha R, Compher C, Gilroy E, Nessel L, Grant A, Chehoud C, Li H, Wu GD, Bushman FD.: Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease. Cell Host Microbe 22(2): 247, August 2017.

Chehoud C, Dryga A, Hwang Y, Nagy-Szakal D, Hollister EB, Luna RA, Versalovic J, Kellermayer R, Bushman FD: Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation. mBio 7(2): e00322, Mar 2016.

Gupta K, Turkki V, Sherrill-Mix S, Hwang Y, Eilers G, Taylor L, McDanal C, Wang P, Temelkoff D, Nolte RT, Velthuisen E, Jeffrey J, Van Duyne GD, Bushman FD: Structural Basis for Inhibitor-Induced Aggregation of HIV Integrase. PLoS biology 14(12): e1002584, Dec 2016.

Liang X, Bittinger K, Li X, Abernethy DR, Bushman FD, FitzGerald GA: Bidirectional interactions between indomethacin and the murine intestinal microbiota. eLife 4: e08973, Dec 2015.

Bushman Frederic D: Engineering the human genome: reflections on the beginning. Human Gene Therapy 25(5): 395-400, May 2014.

Minot S, Grunberg S, Wu GD, Lewis JD, Bushman FD: Hypervariable loci in the human gut virome. Proc. Natl. Acad. Sci. USA 109: 3962-3966, 2012.

Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD: Linking long-term dietary patterns with gut microbial enterotypes. Science 334: 105-108, 2011.

Schröder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F: HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110: 521-529, 2002 Notes: see also cover.

Bushman FD, Fujiwara T, Craigie R: Retroviral DNA integration directed by HIV integration protein in vitro. Science 249: 1555-1558, 1990.

Bushman FD, Anderson JE, Harrison SC, Ptashne M: Ethylation interference and X-ray crystallography identify similar interactions between 434 repressor and operator. Nature 316: 651-653, 1985.

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Last updated: 12/12/2017
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