Joanne Engel, MD, PhD

Professor

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.
Education
Clinical and postdoctoral fellowship, 1990 - Infectious Disease, University of California, San Francisco
Residency, 1986 - Internal Medicine, University of Pennsylvania
M.D., PH.D., 1983 - School of Medicine, Stanford University
Publications

  1. Pha K, Mirrashidi K, Sherry J, Tran CJ, Herrera CM, McMahon E, Elwell CA, Engel JN. The Chlamydia effector IncE employs two short linear motifs to reprogram host vesicle trafficking. 2024. PMID: 39154341


  2. Steiert B, Andersen SE, McCaslin PN, Elwell CA, Faris R, Tijerina X, Smith P, Eldridge Q, Imai BS, Arrington JV, Yau PM, Mirrashidi KM, Johnson JR, Verschueren E, Von Dollen J, Jang GM, Krogan NJ, Engel JN, Weber MM. Global mapping of the Chlamydia trachomatis conventional secreted effector - host interactome reveals CebN interacts with nucleoporins and Rae1 to impede STAT1 nuclear translocation. 2024. PMID: 38712050


  3. Pha K, Mirrashidi K, Sherry J, Tran CJ, Herrera CM, McMahon E, Elwell CA, Engel JN. The Chlamydia effector IncE employs two short linear motifs to reprogram host vesicle trafficking. 2024. PMID: 38712241


  4. Patino R, Kühn MJ, Macmillan H, Inclan YF, Chavez I, Von Dollen J, Johnson JR, Swaney DL, Krogan NJ, Persat A, Engel JN. Spatial control of sensory adaptation modulates mechanosensing in Pseudomonas aeruginosa. 2024. PMID: 38464290


  5. Alexandre M. Sorlin, Marina Lo´pez-A´lvarez, Jacob Biboy, Joe Gray, Sarah J. Rabbitt, Junaid Ur Rahim, Sang Hee Lee, Kondapa Naidu Bobba, Joseph Blecha, Mathew F.L. Parker, Robert R. Flavell, Joanne Engel, Michael Ohliger, Waldemar Vollmer, David M. Wilson. Peptidoglycan-Targeted [18F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection. 2024. PMID:


  6. K?hn MJ, Macmillan H, Tal? L, Inclan Y, Patino R, Pierrat X, Al-Mayyah Z, Engel JN, Persat A. Two antagonistic response regulators control Pseudomonas aeruginosa polarization during mechanotaxis. 2023. PMID: 36795017


  7. Polvoy I, Seo Y, Parker M, Stewart M, Siddiqua K, Manacsa HS, Ravanfar V, Blecha J, Hope TA, Vanbrocklin H, Flavell RR, Barry J, Hansen E, Villanueva-Meyer JE, Engel J, Rosenberg OS, Wilson DM, Ohliger MA. Imaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans. 2022. PMID: 35732972


  8. Kühn MJ, Talà L, Inclan YF, Patino R, Pierrat X, Vos I, Al-Mayyah Z, Macmillan H, Negrete J, Engel JN, Persat A. Mechanotaxis directs Pseudomonas aeruginosa twitching motility. 2021. PMID: 34301869


  9. Peters JM, Koo BM, Patino R, Heussler GE, Hearne CC, Qu J, Inclan YF, Hawkins JS, Lu CHS, Silvis MR, Harden MM, Osadnik H, Peters JE, Engel JN, Dutton RJ, Grossman AD, Gross CA, Rosenberg OS. Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi. 2019. PMID: 30617347


  11. Elwell C, Engel J. Emerging Role of Retromer in Modulating Pathogen Growth. 2018. PMID: 29703496


  13. Elwell CA, Czudnochowski N, von Dollen J, Johnson JR, Nakagawa R, Mirrashidi K, Krogan NJ, Engel JN, Rosenberg OS. Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction. 2017. PMID: 28252385


  16. Inclan YF, Persat A, Greninger A, Von Dollen J, Johnson J, Krogan N, Gitai Z, Engel JN. A scaffold protein connects type IV pili with the Chp chemosensory system to mediate activation of virulence signaling in Pseudomonas aeruginosa. 2016. PMID: 27145134


  17. Elwell C, Mirrashidi K, Engel J. Chlamydia cell biology and pathogenesis. 2016. PMID: 27108705


  18. Mirrashidi KM, Elwell CA, Verschueren E, Johnson JR, Frando A, Von Dollen J, Rosenberg O, Gulbahce N, Jang G, Johnson T, Jäger S, Gopalakrishnan AM, Sherry J, Dunn JD, Olive A, Penn B, Shales M, Cox JS, Starnbach MN, Derre I, Valdivia R, Krogan NJ, Engel J. Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection. 2015. PMID: 26118995


  19. Persat A, Inclan YF, Engel JN, Stone HA, Gitai Z. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa. 2015. PMID: 26041805


  20. 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. 2014. PMID: 25375398


  21. 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. 2014. PMID: 24832456


  22. Engel J, Matthay M. Cystic fibrosis epithelial cell and bacterial binding. 2013. PMID: 24310120


  23. Bucior I, Abbott J, Song Y, Matthay MA, Engel JN. Sugar administration is an effective adjunctive therapy in the treatment of Pseudomonas aeruginosa pneumonia. 2013. PMID: 23792737


  24. Bastidas RJ, Elwell CA, Engel JN, Valdivia RH. Chlamydial intracellular survival strategies. 2013. PMID: 23637308


  25. 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. 2013. PMID: 23480519


  26. Elwell CA, Engel JN. Lipid acquisition by intracellular Chlamydiae. 2012. PMID: 22452394


  28. Kim JH, Jiang S, Elwell CA, Engel JN. Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. 2011. PMID: 21998584


  29. 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. 2011. PMID: 21909260


  32. Wood S, Sivaramakrishnan G, Engel J, Shafikhani SH. Cell migration regulates the kinetics of cytokinesis. 2011. PMID: 21293189


  33. Inclan YF, Huseby MJ, Engel JN. FimL regulates cAMP synthesis in Pseudomonas aeruginosa. 2011. PMID: 21264306


  37. Engel J, Balachandran P. Role of Pseudomonas aeruginosa type III effectors in disease. 2009. PMID: 19168385


  38. Shafikhani SH, Mostov K, Engel J. Focal adhesion components are essential for mammalian cell cytokinesis. 2008. PMID: 18787414


  39. 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. 2008. PMID: 18485000


  41. Elwell CA, Ceesay A, Kim JH, Kalman D, Engel JN. RNA interference screen identifies Abl kinase and PDGFR signaling in Chlamydia trachomatis entry. 2008. PMID: 18369471


  44. Kierbel A, Gassama-Diagne A, Rocha C, Radoshevich L, Olson J, Mostov K, Engel J. Pseudomonas aeruginosa exploits a PIP3-dependent pathway to transform apical into basolateral membrane. 2007. PMID: 17403925


  45. Samuel TK, Gitlin JD. Copper and nitric oxide meet in the plasma. 2006. PMID: 16921354


  47. Agron PG, Reed SL, Engel JN. An essential, putative MEK kinase of Leishmania major. 2005. PMID: 15878208


  49. Whitchurch CB, Beatson SA, Comolli JC, Jakobsen T, Sargent JL, Bertrand JJ, West J, Klausen M, Waite LL, Kang PJ, Tolker-Nielsen T, Mattick JS, Engel JN. Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways. 2005. PMID: 15720546


  50. Gabel BR, Elwell C, van Ijzendoorn SC, Engel JN. Lipid raft-mediated entry is not required for Chlamydia trachomatis infection of cultured epithelial cells. 2004. PMID: 15557670


  51. Gao LY, Guo S, McLaughlin B, Morisaki H, Engel JN, Brown EJ. A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. 2004. PMID: 15341647


  53. Whitchurch CB, Leech AJ, Young MD, Kennedy D, Sargent JL, Bertrand JJ, Semmler AB, Mellick AS, Martin PR, Alm RA, Hobbs M, Beatson SA, Huang B, Nguyen L, Commolli JC, Engel JN, Darzins A, Mattick JS. Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa. 2004. PMID: 15101991


  54. Garrity-Ryan L, Shafikhani S, Balachandran P, Nguyen L, Oza J, Jakobsen T, Sargent J, Fang X, Cordwell S, Matthay MA, Engel JN. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. 2004. PMID: 14688136


  56. Kazmierczak BI, Mostov K, Engel JN. Epithelial cell polarity alters Rho-GTPase responses to Pseudomonas aeruginosa. 2003. PMID: 14595106


  62. Geiser TK, Kazmierczak BI, Garrity-Ryan LK, Matthay MA, Engel JN. Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. 2001. PMID: 11298646


  63. Kazmierczak BI, Jou TS, Mostov K, Engel JN. Rho GTPase activity modulates Pseudomonas aeruginosa internalization by epithelial cells. 2001. PMID: 11207623


  64. Kazmierczak BI, Mostov K, Engel JN. Interaction of bacterial pathogens with polarized epithelium. 2001. PMID: 11544362


  65. van Ooij C, Kalman L, Nishijima M, Hanada K, Mostov K, Engel JN. Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis. 2000. PMID: 11207614


  67. Stephens RS, Fawaz FS, Kennedy KA, Koshiyama K, Nichols B, van Ooij C, Engel JN. Eukaryotic cell uptake of heparin-coated microspheres: a model of host cell invasion by Chlamydia trachomatis. 2000. PMID: 10678910


  73. Hauser AR, Fleiszig S, Kang PJ, Mostov K, Engel JN. Defects in type III secretion correlate with internalization of Pseudomonas aeruginosa by epithelial cells. 1998. PMID: 9529061


  76. Kang PJ, Hauser AR, Apodaca G, Fleiszig SM, Wiener-Kronish J, Mostov K, Engel JN. Identification of Pseudomonas aeruginosa genes required for epithelial cell injury. 1997. PMID: 9218773


  80. Apodaca G, Bomsel M, Lindstedt R, Engel J, Frank D, Mostov KE, Wiener-Kronish J. Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing. 1995. PMID: 7890421


  82. Tan M, Klein R, Grant R, Ganem D, Engel J. Cloning and characterization of the RNA polymerase alpha-subunit operon of Chlamydia trachomatis. 1993. PMID: 8226662


  85. Engel JN, Pollack J, Perara E, Ganem D. Heat shock response of murine Chlamydia trachomatis. 1990. PMID: 2254267


  91. Engel JN, Mellul VG, Goodman DB. Phenytoin hypersensitivity: a case of severe acute rhabdomyolysis. 1986. PMID: 3776999


  92. Engel, JN, Mellul, VG, Goodman, DBP. Phenytoin hypersensitivity: a case of severe acute rhabdomyolysis 1986. PMID:


  93. Ponte, P, Ng, SY, Engel, JN, Kedes, LH. Evolutionary conservation in the untranslated regions of actin mRNA's 1984. PMID:


  96. Kedes, LH, Blau, H, Gunning, P, Ponte, P, Chiu, C-P, Bain, W, Engel, JN, Guttman, S. Molecular genetics of human myogenesis 1983. PMID:


  97. Engel, JN, Gunning, P, Kedes, LH. Human cytoplasmic actin proteins are encoded by a multigene family 1982. PMID:


  98. Engel JN, Gunning PW, Kedes L. Isolation and characterization of human actin genes. 1981. PMID: 6272269


  99. Engel, JN, Gunning, P, Kedes, LH. Isolation and characterization of human actin genes 1981. PMID: