Stanimir S. Ivanov, PhD
Associate Professor of Microbiology and Immunology
Bachelor of Science, Molecular Biology - University of Wisconsin-Parkside
PhD, Biology - Brown University
Post-Doctoral Fellow - Yale University School of Medicine
Immunity to vacuolar bacterial pathogens, pathogen discrimination pathways of the immune system, mechanisms of Legionella pathogenesis, and biogenesis of the Legionella intracellular niche
Faced with an invading microorganism, innate immune cells must rapidly determine its pathogenic potential to tailor their anti-microbial response. For the host, overreaction to avirulent bacteria is just as hazardous as inadequate response to a pathogen. The specialized immune pathways tasked with discriminating innocuous members of the resident microbiota from disease-causing pathogens are fundamentally important for immune function. We use the human pathogen Legionella pneumophila to determine how the process of pathogen discrimination functions at the molecular level. Legionella is the etiological agent of Legionnaires’ disease - a devastating atypical pneumonia. An obligate intracellular pathogen, Legionella manipulates immune phagocytes by injecting over 300 bacterial proteins directly in the host cytoplasm via a type IV secretion system (T4SS). The T4SS promotes Legionella virulence, however it also benefits the host by facilitating pathogen discrimination through the inadvertent release of bacterial molecules in the cytoplasm of infected cells. This process, in turn, promotes the robust inflammatory response required for Legionella clearance. Recently, we uncovered that the central metabolic checkpoint kinase mTOR linked the process of pathogen discrimination with inflammation. Our data support the idea that mTOR functions as a molecular rheostat switch that dials in an appropriate inflammatory response depending upon the treat levels of the invading Legionella. Infections with virulent strains dialed down the rheostat to boost anti-microbial capacity through increased inflammation and autophagy responses; conversely, the rheostat was turned up in response to avirulent strains to maintain the synthesis of anti-inflammatory cytokines and keep inflammation in check. Our research goals are to determine: (i) how signals from immunosurveillance networks modulate the mTOR rheostat during infection; (ii) what factors control the dialing mechanism of the rheostat and (iii) how oscillations in mTOR activity promote asynchronous translation of pro- vs. anti-inflammatory cytokines.
- Edna Ondari, Ashley Wilkins, Brian Latimer, Ana-Maria Dragoi, Stanimir S Ivanov. 2022. Cellular cholesterol licenses Legionella pneumophila intracellular replication in macrophages. Microb Cell 10(1):1-17
- Stanimir S. Ivanov. 2021. Neisseria gonorrhoeae subverts formin-dependent actin polymerization to colonize human macrophages. 17(12): e1010184.
- Ivanov SS. 2017. The tug-of-war over MTOR in Legionella infections. Microb Cell 4(2):67-68
- Abshire CF, Dragoi AM, Roy CR, Ivanov SS. 2016. MTOR-Driven Metabolic Reprogramming Regulates Legionella pneumophila Intracellular Niche Homeostasis. PLoS Pathog 12(12): e1006088.
- Ivanov SS, Roy CR. 2013. Pathogen signatures activate a ubiquitination pathway that modulates function of the metabolic checkpoint kinase mTOR. Nature Immunol 14(12):1219-28.
Dr. Torres-Escobar obtained his Veterinary Medicine and Zootechnics degree (DVM), at the Meritorious Autonomous University of Puebla, México. He received a Master’s degree in Biotechnology from the Biotechnology Institute, and his PhD degree, from the Biomedical Research Institute, both Institutes belong to the National Autonomous University of Mexico, México.
In Dr. Stanimir Ivanov’s research group Dr. Torres-Escobar performs molecular pathogenesis of infection caused by Legionella. His research interests focus on bioinformatic analysis for the characterization of genes and proteins; in the study of pathogenic bacteria and gene regulation; in the construction and application of bacterial genetic engineering against bacterial infectious diseases; cutting-edge technologies in developing recombinant attenuated bacterial vaccine vectors and, in the signaling network essential for regulating biofilm development of bacterial pathogens.
Legionella are Gram-negative intracellular bacteria that parasitize unicellular amoeba that can also infect humans when contaminated aerosolized water droplets are accidentally inhaled and deposited in the lungs. In these accidental pulmonary infections, alveolar macrophages support bacterial replication and promote the development of a severe pneumonia-like illness known as Legionnaire’s disease. To survive within a eukaryotic cell, Legionella creates a unique, membrane-bound organelle known as the Legionella-containing vacuole (LCV). My project focuses on understanding the mechanism(s) which control the expansion of the LCV lipid bilayer during intracellular bacterial replication.
Magdalena Circu, PhD - Lab Manager
Reneau Youngblood - Lab Technician
Postdocs: We are not actively recruiting postdoctoral fellows, but qualified candidates will be considered. Inquiries should be directed to Dr. Ivanov.
Graduate students: Students interested in working in our Department should visit our Graduate Program website.
Undergraduate students: Our Undergraduate Biomedical Research Fellowship program provides bright undergraduates a chance to gain hands-on research experience through a paid internship. More information on our Undergraduate Fellowship Program.