Jeff Schorey George B. Craig Jr. Professor

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 1.5 million deaths annually and is the leading cause of death due to a single infectious organism.  A global threat in recent years has been the significant increase in multi-drug resistant strains of M. tuberculosis. Other pathogenic mycobacteria include M. avium, a major opportunistic pathogen of 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 controlling mycobacterial infections. 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 hope to better understand the virulence mechanisms used by pathogenic mycobacteria. For example, we are presently investigating the importance of glycopeptidolipids (GPLs), a major surface component 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, our lab was the first to show that some mycobacterial components can be released from infected cells via small membrane vesicles called exosomes, and exosomes in turn can modulate the host’s innate and acquired immune response. We continue to characterize this population of exosomes as well as elucidate the importance of exosome biogenesis in M. tuberculosis pathogenesis. In related projects, we are investigating exosomes present in the sera of TB patients as potential diagnostic markers of disease as well as the possible use of exosomes as a novel TB vaccine.   

We also have ongoing studies to evaluate and develop a new class of antibiotics that show potent activity against M. tuberculosis and other pathogenic mycobacteria.  Our goal is to advance these drugs for the treatment of multi-drug resistant strains of M. tuberculosis as well as treatment of non-tuberculosis mycobacterial infections.  The latter group have been particularly difficult to treat with success rates reaching only 50%.  This work is in collaboration with chemist at Notre Dame and with other academic and industrial partners around the world.

We employ 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 and other mycobacterial diseases.

Biography:

• George B. Craig Jr. Collegiate Professor, University of Notre Dame, Notre Dame 2014–Present
• Director, Integrated Biomedical Sciences (IBMS) graduate program 2022–Present
• Professor, Department of Biological Sciences, University of Notre Dame 2010–Present
• Chair, Institutional Animal Care and Use Committee (IACUC) 2008–2018
• Associate Director, Eck Institute for Global Health, University of Notre Dame 2008–2015
• 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:

• McManus WR, Schorey JS. (2023) Comparison of Ultrastructure, Extracellular Matrix, and Drug Susceptibility in M. avium subs. hominissuis Biofilms. Pathogens. Dec 8;12(12):1427.
• Schorey, J.S., Cheng, Y., and McManus, W. (2021) Bacteria- and host-derived extracellular vesicles: Two sides of same coin? J. Cell Science. Jun 1;134(11).
• Cheng, Y. Kiene, N. Tatarian A., Eix, E. and Schorey, J.S (2020) Host Cytosolic RNA Sensing Pathway Promotes T Lymphocyte-mediated Mycobacterial Killing in Macrophages. PLoS Pathogens. May 28;16(5)
• Cheng, Y. and Schorey J.S. (2019) Extracellular vesicles promote host immunity during an M. tuberculosis infection through RNA sensing.  EMBO Reports.  20(3) e46613. (featured in News and View).  
• Li L., Cheng Y., Emrich S., Schorey J.S. (2018) Activation of endothelial cells by extracellular vesicles derived from Mycobacterium tuberculosis infected macrophages or mice. PLoS ONE 13(5) e0198337. 
• Cheng, Y. and Schorey, J.S. (2018) Mycobacterium tuberculosis Induces Type I Interferon Production via a Cross-talk between DNA and RNA Sensing Pathways.  J. Exp Med.  215(11) 2119-2135.  
• Smith, V.L., Cheng, Y., ^†Bryant B.R. and Schorey, J.S. (2017) Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection. Scientific Reports. 7:43578-86.
• G. B. Sigal, M. R. Segal, Leah Jarlsberg, A. Mathew, M. Wang, S. Barbero, N. Small, K. Haynesworth, K. Dobos, N. Kruh-Garcia, L. Davis, M., Weiner, J. Jacobs, J.S. Schorey, D. Lewinsohn, P. Nahid (2017) Biomarkers of Tuberculosis Treatment Effect: A Directed Screen of 70 Biomarkers of Host Response to Infection or Injury in a Randomized Clinical Trial. EBioMedicine. Nov;25:112-121.
• Moraski, G.C., Cheng, Y., Cho, S., Cramer, J.W., Godfrey, A., Masquelin, T., Franzblau, S.G., Miller, M.J. and Schorey, J.S. (2016) Imidazo[1,2-a]pyridine-3-carboxamides are Active Antimicrobial Agents of Mycobacterium avium Infection In Vivo. Antimicrobial Agents and Chemotherapy. Jul 22;60(8):5018-22
• Smith V.L., Jackson, L. and Schorey, J.S. (2015) Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes. 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.