Manuela Raffatellu

Associate Professor, Microbiology & Molecular Genetics
School of Medicine

M.D., University of Sassari, 2000

Phone: (949) 824-0359
Email: manuelar@uci.edu

University of California, Irvine
B251 Med Sci I
Mail Code: 4025
Irvine, CA 92697

picture of Manuela  Raffatellu

Research
Interests
Salmonella pathogenesis, mucosal response to Salmonella,
   
URLs The Raffatellu lab
   
Department of Microbiology and Molecular Genetics
   
Institute for Immunology
   
Academic
Distinctions
2009: The Infectious Diseases Society of America Education and Research Foundation (IDSA ERF) and the National Foundation for Infectious Diseases (NFID) Astellas Young Investigator Award

2009: Keynote lecture at the Swedish Network for Gastrointestinal Infection and Inflammation Workshop, Gothenburg, Sweden

2010: ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) Young Investigator Award

2010-present: Editorial Board of Infection and Immunity

2011 : University of California, Irvine, Chancellor’s Award for Excellence in Fostering Undergraduate Research

2012: Keynote lecture at the Symposium on host-pathogen interaction, Chang Gung Children’s Hospital and Memorial Hospital, Taipei, Taiwan

2013: University of California, Irvine School of Medicine Excellence in Teaching

2013 Keynote lecture at the UC Davis Research Retreat on Host Microbe Interaction, Granlibakken, Tahoe City, CA

2014 Keynote lecture at the UC Berkeley Annual Symposium of the Microbial Student Group

2014 Kavli Frontiers Fellow of the National Academy of Sciences

2014 Keynote lecture at the 6th National Infection Biology Meeting, Marstrand, Sweden

2014 University of California, Irvine School of Medicine Excellence in Teaching

2014 Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease

2014 Special Prize “Candeliere d’oro” 2014, City of Sassari, Italy
   
Appointments 2002-2005 Postdoctoral Research Associate, Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX
Sponsor: Dr. Andreas J. Bäumler

2005-2006 Postdoctoral Research Associate, Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, CA
Sponsor: Dr. Andreas J. Bäumler

2006- 2008 Assistant Project Scientist, Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, CA
   
Research
Abstract
The goal of our research is to understand how mucosal responses are orchestrated in response to mucosal pathogens like Salmonella typhimurium. The mucosal immune response has the important function of containing an infection and preventing dissemination of pathogens to systemic sites. However, there is increasing evidence that mucosal pathogens achieve greater colonization during inflammation. Thus, mucosal responses constitute a double-edge sword: on one end, these responses are necessary to contain an infection to the mucosa, and on the other end they favor pathogens colonization. We are interested in investigating this dichotomy of the host response, and understanding which responses constitute the mucosal barrier during S. typhimurium infection and which ones favor S. typhimurium colonization of the inflamed gut.

Mucosal barrier function during Salmonella infection.

S. typhimurium predominantly causes a localized disease in immunocompetent hosts, characterized by intestinal inflammation and a massive neutrophil influx in the intestinal mucosa. However, in patients with either primary or secondary immune deficiency, including the Acquired Immune Deficiency Syndrome (AIDS), S. typhimurium may cause a life-threatening bacteremia. The focus of my research is on elucidating the role of bacterial virulence factors and host defenses during Salmonella interaction with both immunocompetent and immunocompromised hosts. We have recently found that the mucosal barrier to S. typhimurium is orchestrated by a newly identified set of cytokines, the Th17 cytokines. These cytokines (IL-17A, IL-17F, and IL-22) orchestrate the response to mucosal pathogens and promote barrier function by keeping infection localized to the mucosa, thereby preventing bacteremia. We are further investigating the molecular mechanisms by which the Th17 cytokines mediated barrier function using a variety of in vivo, ex vivo and tissue culture models.

Mechanisms of Salmonella inflammation-adapted life style.

The Th17-mediated inflammatory responses benefit the host and promote resolution of the infection. However, pathogens like S. typhimurium have evolved to survive in the inflamed gut in spite of the host defense mechanisms. Few recent studies have suggested that S. typhimurium exploits inflammation to successfully colonize the gut and achieve host-to-host transmission. We are interested in investigating which bacterial factors and host responses promote colonization of S. typhimurium and other mucosal pathogens. Accessibility of essential nutrients and resistance to antimicrobial peptides are mechanisms that facilitate S. typhimurium colonization of the inflamed gut. We have recently found that resistance to an antimicrobial peptide, lipocalin-2, which mediates iron withholding, facilitates S. typhimurium colonization of the inflamed gut. Thus, the capacity of acquiring iron during inflammation promotes S. typhimurium colonization. We are further studying the mechanisms of metal withholding responses in the gut, and if these responses are exploited by mucosal pathogens like S. typhimurium to achieve greater colonization.
   
Publications Selected publications.
For a complete list:
http://www.ncbi.nlm.nih.gov/sites/entrez?form=4&db=pubmed&term=raffatellu%20m
   
  M. Raffatellu*, R. L. Santos*, D. Verhoeven, M. D. George, R. P. Wilson, S. E. Winter, I. Godinez, S. Sankaran, T. A. Paixao, M. A. Gordon, J. K. Kolls, S. Dandekar, and A, J. Bäumler. Simian immunodeficiency virus-induced mucosal IL-17 deficiency promotes Salmonella dissemination from the gut. (*contributed equally). Nature Medicine. (2008) 14 (4): 421-428.
(Evaluated by Faculty of 1000 Medicine)
http://www.f1000medicine.com/article/id/1104657/evaluation
   
  M. Raffatellu, M.D. George, Y. Akiyama, M.J. Hornsby, S. Nuccio, T. A. Paixão, B. P. Butler, H. Chu, R. L. Santos, T. Berger, T. W. Mak, R.M. Tsolis, C.L. Bevins, J. V. Solnick, S. Dandekar and A.J. Bäumler. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host and Microbe. (2009) 5(5): 476-486.
(Featured Article)
(Preview by Eric Skaar “A precious metal heist”, Cell Host Microbe. 2009 May 8;5(5):422-4.)
(Presented as Research Highlights “Taking iron from the fire”, Nature Reviews Microbiology, 2009 July 7(7): 479.)
   
  J.Z. Liu, M. Pezeshki, and M. Raffatellu. Th17 cytokines and host-pathogen interactions at the mucosa: dichotomies of help and harm. Cytokine.(2009) Oct-Nov; 48(1-2): 156-160.
   
  M. Raffatellu and A. J. Bäumler. Salmonella’s iron armor for battling the host and its microbiota. Gut Microbes. (2010) Vol1 (1); Jan-Feb; 36-38
   
  C. Blaschitz and M. Raffatellu. Th17 cytokines and the gut mucosal barrier. Journal of Clinical Immunology. (2010) Mar; 30(2):196-203
   
  S-S Yim, L. Yousef, C. Blaschitz, J. Z. Liu, R. A. Edwards, S. G. Young, M. Raffatellu, and T. F. Osborne. Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein -1a. Cell Metabolism 13, 1-10, May 4, 2011.
(Selected as a Featured article)
(Presented as Research highlights "Linking lipids and Inflammasomes" in Nature Reviews Immunology, Vol 11, June 2011)
(Evaluated by Faculty of 1000 as “Must Read”, 8)
   
  J. Z. Liu, S. Jellbauer, A. Poe, M. Pesciaroli, T. Kehl-Fie, N. A. Restrepo, M. Hosking, R. A. Edwards, A. Battistoni, P. Pasquali, T. E. Lane, W. Chazin, T. Vogl, J. Roth, E. P. Skaar, and M. Raffatellu. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host and Microbe. (2012) March; 11 (3); 227-239
(Selected as Featured article)
(Selected as Editor’s choice, “In need of nutrients”, Science, Vol 335, March 2012)
(Presented as Research Highlights ”A competitive edge for Salmonella”, Nature Reviews Microbiology)
(Evaluated by Faculty of 1000 as “Must Read”, 8)
   
  N. D. Vaziri, N. Ghoshtasby, J. Yuan, S. Jellbauer, H. Moradi, M. Raffatellu, Kamyar Kalantar-Zadeh. Uremic human plasma degrades intestinal epithelial barrier structure and function. American Journal of Nephrology. 2012 Oct 31;36(5):438-443
   
  M. M. Bellet+, E. Deriu+, J. Z. Liu, B. Grimaldi, C. Blaschitz, M. Keller, R. A. Edwards, S. Sahar, S. Dandekar, P. Baldi, M. D. George, M. Raffatellu*, and P. Sassone-Corsi*.(+co-first authors *co-senior authors). Circadian clock regulates the host response to Salmonella. Proceedings of the National Academy of Science. 2013 Jun 11;110(24):9897-902
   
  M. Pesciaroli, M. Gradassi, M.G. Zanoni, N. Martinelli, N. Ruggeri, C. Pistoia, P. Petrucci, G. Lombardi, S. Ammendola, M. Raffatellu, C.F. Magistrali, A. Battistoni, and P. Pasquali. Salmonella Typhimurium lacking the ZnuABC transporter is attenuated and immunogenic in pigs. Vaccine. 2013. Jun 12;31(27):2868-73
   
  J. Behnsen, E. Deriu, M. Sassone-Corsi, and M. Raffatellu. Probiotics: properties, examples and specific applications. In: Bacterial Pathogenesis, CSHL Perspectives in Medicine. Editors: Pascale Cossart and Stanley Maloy.(2013) Mar 1;3(3).
(Selected as Featured article)
   
  M. Gradassi, M. Pesciaroli, M.G. Zanoni, N. Martinelli, N. Ruggeri, C. Pistoia, P. Petrucci, G. Lombardi, W. Hamdy, S. Ammendola, M. Raffatellu, A. Battistoni, G.L. Alborali, and P. Pasquali. Attenuated Salmonella enterica serovar Typhimurium lacking the ZnuABC transporter: an efficacious orally-administered mucosal vaccine against salmonellosis in pigs. Vaccine. (2013) Aug 12;31(36):3695-701
   
  J. Behnsen and M. Raffatellu. Keeping the peace: aryl hydrocarbon receptor signaling modulates the mucosal microbiota. Immunity. (2013) Aug 22;39(2):206-7.
   
  S. Jellbauer and M. Raffatellu. An intestinal arsonist: pathobiont ignites IBD and flees the scene. Gut. (2013) Sep 11. (Epub ahead of print).
   
  E. Deriu, J. Z. Liu, M. Pezeshki, R. Ochoa, H. Contreras, R. A. Edwards, S. Libby, F. Fang, and M. Raffatellu. Probiotic bacteria reduce Salmonella Typhimurium intestinal colonization by competing for iron. Cell Host and Microbe. (2013) July; 14; 26-37
(Selected for cover image)
(Selected as Featured article)
(Preview by Guenther Weiss ”Intestinal irony: how probiotic bacteria outcompete bad bugs”, Cell Host and Microbe. (2013) July 17(14)pg3-4)
(Discussed by This Week in Microbiology, podcast, August 2013)
(Selected as Editor’s choice “Good and bad bacteria fight for iron in the gut”, Science Translational Medicine, August 2013)
   
  M. Sassone-Corsi and M. Raffatellu. A hydrogen boost for Salmonella. Cell Host and Microbe (2013) Dec; 14; 603-604.
   
  M. Cerasi, J. Z. Liu, S. Ammendola, A. J. Poe, P. Petrarca, M. Pesciaroli, P. Pasquali, M. Raffatellu, A. Battistoni. The ZupT transporter plays a central role in zinc homeostasis and contributes to Salmonella enterica virulence. Metallomics. 2014 Jan 16. [Epub ahead of print]
   
  V. E. Diaz-Ochoa, S. Jellbauer, S. Klaus, and M. Raffatellu. Transition Metal Ions at the Crossroads of Mucosal Immunity and Microbial Pathogenesis. Frontiers in Cellular and Infection Microbiology. 2014 Jan 24;4:2. eCollection 2014.
   
  J. Behnsen, S. Jellbauer, C. P. Wong, R. A. Edwards, M. D. George, W. Ouyang, and M. Raffatellu. The Cytokine IL-22 Promotes Pathogen Colonization by Suppressing Related Commensal Bacteria. Immunity (2014), http://dx.doi.org/10.1016/j.immuni.2014.01.003
(Selected as Featured article)
(Preview by Denise Monack “The battle in the gut”, Immunity. (2014) Feb 20;40(2):173-5
   
Grants AI083663 R01 Award from NIH, National Inst. of Allergy and Infectious Disease (primary) And National Inst. of Diabetes and Digestive and Kidney Disease Project title: Mucosal barrier function during Salmonella infection Role on project: PI Effective and exp.dates: 1/2010-12/2014
   
AI105374 (MPI) Raffatellu (PI) R21 Award from NIH, National Inst. of Allergy and Infectious Disease Project title: The role of the circadian clock during Salmonella infection Role: PI (Co-PI, Dr. Paolo Sassone-Corsi) Effective and exp.dates: 12/2013-11/2015
   
AI101784-01 (MPI) Raffatellu (PI) R21 Award from NIH, National Inst. of Allergy and Infectious Disease Project title: Targeting Iron Acquisition in Salmonella with Siderophore-based Immunization Role: PI (Co-PI, Dr. Elizabeth Nolan) Effective and exp.dates: 07/2014-06/2016
   
Burroughs Wellcome Funds Raffatellu (PI) Pathogenesis of Infectious Disease Award Project title: Characterization of novel populations of neutrophils during bacterial infection Role: PI Effective and exp.dates: 07/2014-06/2019
   
Graduate Programs Cellular and Molecular Biosciences

   
Research Center Institute for Immunology
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=5823
   
Last updated 09/03/2014