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. 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. bioRxiv : the preprint server for biology 2024. PMID: 38712050


  2. 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. bioRxiv : the preprint server for biology 2024. PMID: 38712241


  3. 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. bioRxiv : the preprint server for biology 2024. PMID: 38464290


  4. 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. Prioritizing post-COVID-19 health research in sub-Saharan Africa: A modified Delphi study for future pandemics. 2024. PMID:


  5. 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. The EMBO journal 2023. PMID: 36795017


  6. 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. European journal of nuclear medicine and molecular imaging 2022. PMID: 35732972


  7. 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. Proceedings of the National Academy of Sciences of the United States of America 2021. PMID: 34301869


  8. 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. Nature microbiology 2019. PMID: 30617347


  9. Kumagai K, Elwell CA, Ando S, Engel JN, Hanada K. Both the N- and C- terminal regions of the Chlamydial inclusion protein D (IncD) are required for interaction with the pleckstrin homology domain of the ceramide transport protein CERT. Biochemical and biophysical research communications 2018. PMID: 30314703


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


  11. Ruch TR, Engel JN. Targeting the Mucosal Barrier: How Pathogens Modulate the Cellular Polarity Network. Cold Spring Harbor perspectives in biology 2017. PMID: 28193722


  12. 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. eLife 2017. PMID: 28252385


  13. Ruch TR, Bryant DM, Mostov KE, Engel JN. Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity. Molecular biology of the cell 2016. PMID: 27881661


  14. 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. Molecular microbiology 2016. PMID: 27145134


  15. Elwell C, Mirrashidi K, Engel J. Chlamydia cell biology and pathogenesis. Nature reviews. Microbiology 2016. PMID: 27108705


  16. 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. Cell host & microbe 2015. PMID: 26118995


  17. Persat A, Inclan YF, Engel JN, Stone HA, Gitai Z. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the United States of America 2015. PMID: 26041805


  18. 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 pathogens 2014. PMID: 25375398


  19. 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. PMID: 24832456


  20. Engel J, Matthay M. Cystic fibrosis epithelial cell and bacterial binding. American journal of physiology. Lung cellular and molecular physiology 2013. PMID: 24310120


  21. Bucior I, Abbott J, Song Y, Matthay MA, Engel JN. Sugar administration is an effective adjunctive therapy in the treatment of Pseudomonas aeruginosa pneumonia. American journal of physiology. Lung cellular and molecular physiology 2013. PMID: 23792737


  22. Bastidas RJ, Elwell CA, Engel JN, Valdivia RH. Chlamydial intracellular survival strategies. Cold Spring Harbor perspectives in medicine 2013. PMID: 23637308


  23. 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. Cellular microbiology 2013. PMID: 23480519


  24. Elwell CA, Engel JN. Lipid acquisition by intracellular Chlamydiae. Cellular microbiology 2012. PMID: 22452394


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


  26. 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 pathogens 2011. PMID: 21909260


  27. Engel J, Eran Y. Subversion of mucosal barrier polarity by pseudomonas aeruginosa. Frontiers in microbiology 2011. PMID: 21747810


  28. Wood S, Sivaramakrishnan G, Engel J, Shafikhani SH. Cell migration regulates the kinetics of cytokinesis. Cell cycle (Georgetown, Tex.) 2011. PMID: 21293189


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


  30. Bertrand JJ, West JT, Engel JN. Genetic analysis of the regulation of type IV pilus function by the Chp chemosensory system of Pseudomonas aeruginosa. Journal of bacteriology 2009. PMID: 20008072


  31. Endoh T, Engel JN. CbpA: a polarly localized novel cyclic AMP-binding protein in Pseudomonas aeruginosa. Journal of bacteriology 2009. PMID: 19801409


  32. Engel J, Balachandran P. Role of Pseudomonas aeruginosa type III effectors in disease. Current opinion in microbiology 2009. PMID: 19168385


  33. Shafikhani SH, Mostov K, Engel J. Focal adhesion components are essential for mammalian cell cytokinesis. Cell cycle (Georgetown, Tex.) 2008. PMID: 18787414


  34. 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. Environmental microbiology 2008. PMID: 18485000


  35. Pielage JF, Powell KR, Kalman D, Engel JN. RNAi screen reveals an Abl kinase-dependent host cell pathway involved in Pseudomonas aeruginosa internalization. PLoS pathogens 2008. PMID: 18369477


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


  37. Brandt S, Shafikhani S, Balachandran P, Jin S, Hartig R, König W, Engel J, Backert S. Use of a novel coinfection system reveals a role for Rac1, H-Ras, and CrkII phosphorylation in Helicobacter pylori-induced host cell actin cytoskeletal rearrangements. FEMS immunology and medical microbiology 2007. PMID: 17428306


  38. 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. The Journal of cell biology 2007. PMID: 17403925


  39. Samuel TK, Gitlin JD. Copper and nitric oxide meet in the plasma. Nature chemical biology 2006. PMID: 16921354


  40. Elwell C, Engel JN. Drosophila melanogaster S2 cells: a model system to study Chlamydia interaction with host cells. Cellular microbiology 2005. PMID: 15839901


  41. Agron PG, Reed SL, Engel JN. An essential, putative MEK kinase of Leishmania major. Molecular and biochemical parasitology 2005. PMID: 15878208


  42. Kierbel A, Gassama-Diagne A, Mostov K, Engel JN. The phosphoinositol-3-kinase-protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization. Molecular biology of the cell 2005. PMID: 15772151


  43. 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. Molecular microbiology 2005. PMID: 15720546


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


  45. 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. Molecular microbiology 2004. PMID: 15341647


  46. Engel J. Tarp and Arp: How Chlamydia induces its own entry. Proceedings of the National Academy of Sciences of the United States of America 2004. PMID: 15226494


  47. 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. Molecular microbiology 2004. PMID: 15101991


  48. 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. Infection and immunity 2004. PMID: 14688136


  49. B. McMorran, L. Town, E. Costelloe, J. Palmer, J. Engel, D. Hume, B. Wainwright. Effector ExoU from the Type III Secretion System Is An Important Modulator of Gene Expression in Lung Epithelial Cells in Response to Pseudomonas aeruginosa Infection. Infection and immunity 2003. PMID:


  50. Kazmierczak BI, Mostov K, Engel JN. Epithelial cell polarity alters Rho-GTPase responses to Pseudomonas aeruginosa. Molecular biology of the cell 2003. PMID: 14595106


  51. McMorran B, Town L, Costelloe E, Palmer J, Engel J, Hume D, Wainwright B. Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection. Infection and immunity 2003. PMID: 14500525


  52. Jacob T, Lee RJ, Engel JN, Machen TE. Modulation of cytosolic Ca(2+) concentration in airway epithelial cells by Pseudomonas aeruginosa. Infection and immunity 2002. PMID: 12379720


  53. Kazmierczak BI, Engel JN. Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA, Rac1, and Cdc42. Infection and immunity 2002. PMID: 11895987


  54. Hauser AR, Cobb E, Bodi M, Mariscal D, Vallés J, Engel JN, Rello J. Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Critical care medicine 2002. PMID: 11990909


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


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


  57. Kazmierczak BI, Mostov K, Engel JN. Interaction of bacterial pathogens with polarized epithelium. Annual review of microbiology 2001. PMID: 11544362


  58. 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. Cellular microbiology 2000. PMID: 11207614


  59. 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. Infection and immunity 2000. PMID: 10678910


  60. Comolli JC, Waite LL, Mostov KE, Engel JN. Pili binding to asialo-GM1 on epithelial cells can mediate cytotoxicity or bacterial internalization by Pseudomonas aeruginosa. Infection and immunity 1999. PMID: 10377092


  61. Comolli JC, Hauser AR, Waite L, Whitchurch CB, Mattick JS, Engel JN. Pseudomonas aeruginosa gene products PilT and PilU are required for cytotoxicity in vitro and virulence in a mouse model of acute pneumonia. Infection and immunity 1999. PMID: 10377148


  62. Van Ooij C, Homola E, Kincaid E, Engel J. Fusion of Chlamydia trachomatis-containing inclusions is inhibited at low temperatures and requires bacterial protein synthesis. Infection and immunity 1998. PMID: 9784545


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


  64. Hauser AR, Kang PJ, Engel JN. PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity and virulence. Molecular microbiology 1998. PMID: 9515706


  65. Fawaz FS, van Ooij C, Homola E, Mutka SC, Engel JN. Infection with Chlamydia trachomatis alters the tyrosine phosphorylation and/or localization of several host cell proteins including cortactin. Infection and immunity 1997. PMID: 9393830


  66. 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. Molecular microbiology 1997. PMID: 9218773


  67. Tan M, Wong B, Engel JN. Transcriptional organization and regulation of the dnaK and groE operons of Chlamydia trachomatis. Journal of bacteriology 1996. PMID: 8955323


  68. 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. Infection and immunity 1995. PMID: 7890421


  69. Dell KR, Engel JN. Stage-specific regulation of protein phosphorylation in Leishmania major. Molecular and biochemical parasitology 1994. PMID: 7935606


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


  71. Engel JN. Azithromycin-induced block of elementary body formation in Chlamydia trachomatis. Antimicrobial agents and chemotherapy 1992. PMID: 1280057


  72. Perara E, Ganem D, Engel JN. A developmentally regulated chlamydial gene with apparent homology to eukaryotic histone H1. Proceedings of the National Academy of Sciences of the United States of America 1992. PMID: 1549572


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


  74. Engel JN, Pollack J, Malik F, Ganem D. Cloning and characterization of RNA polymerase core subunits of Chlamydia trachomatis by using the polymerase chain reaction. Journal of bacteriology 1990. PMID: 2211507


  75. Engel JN, Ganem D. Chlamydial rRNA operons: gene organization and identification of putative tandem promoters. Journal of bacteriology 1987. PMID: 2445732


  76. Engel JN, Mellul VG, Goodman DB. Phenytoin hypersensitivity: a case of severe acute rhabdomyolysis. The American journal of medicine 1986. PMID: 3776999


  77. Engel, JN, Mellul, VG, Goodman, DBP. Phenytoin hypersensitivity: a case of severe acute rhabdomyolysis American Journal of Medicine 1986. PMID:


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


  79. Engel, JN. Isolation and characterization of human actin genes. Ph.D. Dissertation, Stanford University Isolation and characterization of human actin genes. Ph.D. Dissertation, Stanford University 1983. PMID:


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


  81. Engel, JN, Gunning, P, Kedes, LH. Human cytoplasmic actin proteins are encoded by a multigene family Molecular and cellular biology 1982. PMID:


  82. Engel JN, Gunning PW, Kedes L. Isolation and characterization of human actin genes. Proceedings of the National Academy of Sciences of the United States of America 1981. PMID: 6272269


  83. Engel, JN, Gunning, P, Kedes, LH. Isolation and characterization of human actin genes Proceedings National Academy of Sciences 1981. PMID: