Joanne Engel, MD, PhD

Chief, Division of Infectious Disease, Department of Medicine
Director, Microbial Pathogenesis and Host Defense Program
Professor
Department of Medicine
Research Description: 

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.

Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Immunology
Research Summary: 
Bacterial host-Cell Interactions
Mentorship Development: 

11/23/20    Building Community in the UCSF MSTP

Websites

Publications: 

Spatial control of sensory adaptation modulates mechanosensing in Pseudomonas aeruginosa.

bioRxiv : the preprint server for biology

Patino R, Kühn MJ, Macmillan H, Inclan YF, Chavez I, Von Dollen J, Johnson JR, Swaney DL, Krogan NJ, Persat A, Engel JN

Peptidoglycan-Targeted [18F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection.

JACS Au

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

Two antagonistic response regulators control Pseudomonas aeruginosa polarization during mechanotaxis.

The EMBO journal

K?hn MJ, Macmillan H, Tal? L, Inclan Y, Patino R, Pierrat X, Al-Mayyah Z, Engel JN, Persat A

Imaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans.

European journal of nuclear medicine and molecular imaging

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

Mechanotaxis directs Pseudomonas aeruginosa twitching motility.

Proceedings of the National Academy of Sciences of the United States of America

Kühn MJ, Talà L, Inclan YF, Patino R, Pierrat X, Vos I, Al-Mayyah Z, Macmillan H, Negrete J, Engel JN, Persat A