Jeff Schorey George B. Craig Jr. Professor

Pathobiology of Mycobacterial Diseases
Jeff Schorey

Research Interests:

Mycobacterial species have a long history as human and animal pathogens and are the etiological agents of diseases such as tuberculosis and leprosy. Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is a particularly deadly disease accounting for approximately 1.4 million deaths annually and is the second leading cause of death due to an infectious organism. A global threat in recent years has been the dramatic increase in the number of multi-drug resistant strains of M. tuberculosis. Other pathogenic mycobacteria include M. avium, a major opportunistic pathogen infecting AIDS patients in the United States, and now increasingly associated with COPD and Cystic Fibrosis patients.

Our research focuses on the interaction between mycobacteria and the macrophage--the major cell in the body infected by mycobacteria. Activated macrophages, which function as an important component of the innate immune system, also play a vital role in the control of a mycobacterial infection. We are interested in defining the molecular interactions between the macrophage and mycobacteria. Ongoing studies aim at characterizing the macrophage signaling pathways activated upon infection by pathogenic and non-pathogenic mycobacteria species/strains and in doing so, we seek to better understand the virulence mechanisms used by pathogenic mycobacteria. For example, we are presently investigating the importance of glycopeptidolipids, major surface components of M. avium, in modulating the macrophage-signaling response.

Another major line of investigation is deciphering the role of secreted exosomes in disease transmission. Using cell and animal models, we showed that some mycobacterial components can be released from infected cells via small membrane vesicles called exosomes, and that the released exosomes modulate the host’s innate and acquired immune response. We continue to characterize this population of exosomes as well as elucidate the importance of their biogenesis in M. tuberculosis pathogenesis. In a related project, supported by the Bill and Melinda Gates Foundation, we are investigating whether exosomes, which are present in human TB patient serum, can be used as diagnostic markers of disease. We are also evaluating exosomes as potential TB vaccines.

We utilize cellular and immunological experimental approaches in combination with whole animal studies and the analyses of clinical samples. The goal of our research is to help control mycobacterial infections through a better understanding of Mycobacterium-host interactions and develop the next-generation of diagnostic tools, vaccines and antibiotics directed toward eradicating TB.

 

Biography:

  • George B. Craig Jr. Professor of Biological Sciences 2014 - present
  • Professor, Department of Biological Sciences, University of Notre Dame 2010 – present
  • Associate Professor, Department of Biological Sciences, University of Notre Dame 2004 – 2010
  • Assistant Professor, Department of Biological Sciences, University of Notre Dame 1998 – 2004
  • Instructor of Medicine, Washington University School of Medicine, St. Louis, MO. 1996 – 1998
  • Post-Doctoral Fellow, Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO. 1993 – 1996
  • Ph.D., University of Texas Health Science Center, San Antonio Texas 1992

 

Selected Papers:

  • Smith V.L., Jackson, L. and Schorey, J.S. (2015) Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes. J. Immunol. 195(6):2722-30.
  • Schorey J.S., Cheng Y., Singh P.P., Smith V.L., (2015) Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep. 16(1):24-43.
  • Singh, P.P., *Li, L. and Schorey, J.S. (2015). Exosomal RNA from Mycobacterium tuberculosis infected cells is functional in recipient macrophages. Traffic. 16(6) 555-571.
  • Kruh-Garcia NA, Wolfe LM, Chaisson LH, Worodria WO, Nahid P, Schorey JS, Davis JL, Dobos KM (2014) Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS. PLoS One. 9(7):e103811.
  • Cheng, Y. Moraski, G.C. Cramer, J. Miller, M.J. and Schorey, J.S. (2014) Bactericidal Activity of an Imidazo[1, 2-a]pyridine Using a Mouse M. tuberculosis Infection Model. PLoS ONE, 9(1) e87483.
  • Cheng, Y. and Schorey, J.S. (2013) Exosomes carrying mycobacterial antigens can protect mice against an M. tuberculosis Infection. European Journal of Immunology. 43 (12) 3279-3290.
  • Giri, P.K., Kruh, N.A., Dobos, K.M. and Schorey, J.S. (2010) Proteomic analysis identifies highly antigenic proteins on exosomes from M. tuberculosis-infected and culture filtrate protein-treated macrophages. Proteomics. 10; 3190-3202.
  • Yadav, M. and Schorey, J.S. (2006) The β-glucan receptor Dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood. 108; 3168-3175.
  • Krzywinska, E., Bhatnagar, S., *Sweet, L., Chatterjee, D. and Schorey, J.S. (2005) Modification of Mycobacterium avium glycopeptidolipid structure results in bacilli of attenuated virulence. Molecular Microbiology. 56; 1262-1273.
  • Kelley, V.A. and Schorey, J.S. (2003) Endosome Fusion and Iron Acquisition is Required for Mycobacterial Retention in an Early Phagosomal Compartment in Primary Macrophages. Molecular Biology of the Cell. 14; 3366-77.
  • Bohlson, S.S., Strasser, J.A., Bower, J.J., and Schorey, J.S. (2001) The role of complement in Mycobacterium avium pathogenesis: In vivo and in vitro analysis of the host response to infection in the absence of complement component C3. Infection & Immunity. 69; 7729-7735.
  • Schorey, J.S., Carroll, M.C. and Brown, E.J. (1997) A macrophage invasion mechanism of pathogenic mycobacteria. Science. 277; 1091-1093.