Joanne Netter Engel, MD, PhD

Joanne Netter Engel, MD, PhD

Professor, Departments of Medicine and Microbiology/Immunology, UCSF

Phone: (415) 476-7355 (voice)
Box 0654, UCSF
San Francisco, CA 94143-0654

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Cancer Center Membership

Associate Member » Non-aligned

Research Summary

My lab is interested in the complex interplay between bacterial pathogens and host cells. In particular, we study two important human pathogens, Chlamydia trachomatis and Pseudomonas aeruginosa. Our strengths include using multidisciplinary approaches to these studies—allowing the pathogen to be our tutor. We have utilized bacterial genetics and genetic screens, molecular biology, cellular microbiology, host cell biology with advanced immunofluorescence microscopy, genome-wide RNAi screens, bioinformatics, and proteomics to rigorously understand the mechanisms by which they subvert host cell functions to cause disease. Seminal contributions that our group has made to the study of P. aeruginosa-host interactions is (i) the discovery of the P. aeruginosa type III secretion system and one of the secreted effectors ExoU and the demonstration that the P. aeruginosa type III secretion system is important for virulence in cell-culture, mouse, and human infections (ii) demonstrating that the type III secreted toxin ExoT inhibits wound repair through redundant pathways (iii) elucidation of the pathway by which P. aeruginosa can be internalized by non-phagocytic cells and how the type III secretion system-encoded effectors modulate entry (iv) characterization of novel genes involved in type IV pilin biogenesis and in the regulation of diverse virulence pathways (v) the first identification of a host cell ubiquitin ligase (cbl-b) that specifically targets the degradation of a type III secreted factor (vii) development of 2D and 3D cell-culture based systems to dissect the interaction of pathogens with the apical versus basolateral surface of polarized epithelial cells (vi) discovery that upon binding to the apical surface of polarized epithelial cells, P. aeruginosa forms biofilm-like structures that are able to transform apical membrane into basolateral membrane by exploiting the phosphatidyl inositol kinase pathway to form membrane protrusions that are associated with a spatial and temporal activation of the innate immune response. Our current studies focus on the dissection of the Chp/Vfr/ regulatory pathway that regulates diverse virulence factor circuits in P. aeruginosa in determining the bacterial and host determinants involved in the formation of biofilms and spatially localized activation of the innate immune response at the apical surface of tissues. In our studies on the pathogenesis of chlamydial infections, we have focused on host cell biology and genome-wide RNA-based screens to understanding how C. trachomatis modulates host cell signaling systems to bind, enter, and establish a replicative niche. We have carried out a genome wide RNAi screen in a simple genetic host and have identified new host molecules that are involved in binding, entry, and establishment of a unique intracellular niche. We have discovered a potential role for host growth factors in binding and entry and elucidated a novel pathway by which this organism acquires sphingolipids from the host. We have complemented these studies with state of the art confocal microscopy to begin to elucidate the bacterial and host determinants and mechanism of vacuole fusion. We are currently carrying out high throughput proteomics to dissect the function of the approximately 150 proteins that Chlamydia inject into the host cell to create a unique replicative niche and to escape the innate immune response.


Yale University, New Haven, CT, B.S., 1976, Biochemistry
Stanford University, Palo Alto, CA, Ph.D., 1982, Biophysics
Stanford University, Palo Alto, CA, M.D., 1983, Medicine

Professional Experience

  • June 1983 - June 1984
    Hospital of the University of Pennsylvania,Internship, Department of Medicine
  • June 1984 - Jan 1986
    Hospital of the University of Pennsylvania, Residency, Department of Medicine
  • Jan 1986 - July 1986
    Residency, Department of Medicine, UCSF
  • July 1986 - June 1990
    Clinical and Postdoctoral Fellowship, Div. of Infectious Diseases, Department of Microbiology and Immunology, UCSF
  • July 1990 - June 1998
    Assistant Professor in Residence, Div. of Infectious Diseases, Department of Medicine, UCSF
  • July 1998 - June 2004
    Associate Professor, Division of Infectious Disease and Department of Microbiology and Immunology
  • July 2004 - present
    Professor in Residence, University of California, San Francisco, Depts. of Medicine and Microbiology and Immunology
  • July 2004 - present
    Director, Microbial Pathogenesis and Host Defense Program
  • January 2005 - present
    Interim Chief, Division of Infectious Disease

Honors & Awards

  • 1976
    Phi Beta Kappa
  • 1976
    Sigma Xi
  • 1976
    Magna cum laude, Yale University
  • 1977
    Medical Scientist Training Program
  • 1988
    Lucille Markey Biomedical Scholar
  • 1994
    NIH Career Development Award
  • 1998
    American Lung Association Career Investigator
  • 2004
    President-Elect, Division B of American Society for Microbiology

Selected Publications

  1. Persat A, Inclan YF, Engel JN, Stone HA, Gitai Z. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2015 Jun 16; 112(24):7563-8.
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  2. Tran CS, Rangel SM, Almblad H, Kierbel A, Givskov M, Tolker-Nielsen T, Hauser AR, Engel JN. The Pseudomonas aeruginosa Type III Translocon Is Required for Biofilm Formation at the Epithelial Barrier. PLoS Pathog. 2014 Nov; 10(11):e1004479.
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  3. Tran CS, Eran Y, Ruch TR, Bryant DM, Datta A, Brakeman P, Kierbel A, Wittmann T, Metzger RJ, Mostov KE, Engel JN. Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Cell Host Microbe. 2014 May 14; 15(5):636-43.
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  4. Bucior I, Abbott J, Song Y, Matthay MA, Engel JN. Sugar administration is an effective adjunctive therapy in the treatment of Pseudomonas aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol. 2013 Sep; 305(5):L352-63.
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  5. Bastidas RJ, Elwell CA, Engel JN, Valdivia RH. Chlamydial intracellular survival strategies. Cold Spring Harb Perspect Med. 2013 May; 3(5):a010256.
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  6. Kim JH, Chan C, Elwell C, Singer MS, Dierks T, Lemjabbar-Alaoui H, Rosen SD, Engel JN. Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cell Microbiol. 2013 Sep; 15(9):1560-71.
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  7. Elwell CA, Engel JN. Lipid acquisition by intracellular Chlamydiae. Cell Microbiol. 2012 Jul; 14(7):1010-8.
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  8. Bucior I, Pielage JF, Engel JN. Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium. PLoS Pathog. 2012; 8(4):e1002616.
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  9. Kim JH, Jiang S, Elwell CA, Engel JN. Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. PLoS Pathog. 2011 Oct; 7(10):e1002285.
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  10. Elwell CA, Jiang S, Kim JH, Lee A, Wittmann T, Hanada K, Melancon P, Engel JN. Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog. 2011 Sep; 7(9):e1002198.
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  11. Engel J, Eran Y. Subversion of mucosal barrier polarity by pseudomonas aeruginosa. Front Microbiol. 2011; 2:114.
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  12. Elwell CA, Kierbel A, Engel JN. Species-specific interactions of Src family tyrosine kinases regulate Chlamydia intracellular growth and trafficking. MBio. 2011; 2(3):e00082-11.
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  13. Wood S, Sivaramakrishnan G, Engel J, Shafikhani SH. Cell migration regulates the kinetics of cytokinesis. Cell Cycle. 2011 Feb 15; 10(4):648-54.
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  14. Inclan YF, Huseby MJ, Engel JN. FimL regulates cAMP synthesis in Pseudomonas aeruginosa. PLoS One. 2011; 6(1):e15867.
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  15. Bucior I, Mostov K, Engel JN. Pseudomonas aeruginosa-mediated damage requires distinct receptors at the apical and basolateral surfaces of the polarized epithelium. Infect Immun. 2010 Mar; 78(3):939-53.
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  16. Bertrand JJ, West JT, Engel JN. Genetic analysis of the regulation of type IV pilus function by the Chp chemosensory system of Pseudomonas aeruginosa. J Bacteriol. 2010 Feb; 192(4):994-1010.
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  17. Endoh T, Engel JN. CbpA: a polarly localized novel cyclic AMP-binding protein in Pseudomonas aeruginosa. J Bacteriol. 2009 Dec; 191(23):7193-205.
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  18. Engel J, Balachandran P. Role of Pseudomonas aeruginosa type III effectors in disease. Curr Opin Microbiol. 2009 Feb; 12(1):61-6.
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  19. Shafikhani SH, Mostov K, Engel J. Focal adhesion components are essential for mammalian cell cytokinesis. Cell Cycle. 2008 Sep 15; 7(18):2868-76.
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  20. Barken KB, Pamp SJ, Yang L, Gjermansen M, Bertrand JJ, Klausen M, Givskov M, Whitchurch CB, Engel JN, Tolker-Nielsen T. Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. Environ Microbiol. 2008 Sep; 10(9):2331-43.
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