Patricia Champion Associate Professor

Molecular Genetics of Mycobacterial Pathogenesis
Patricia Champion

Research Interests:

Pathogenic mycobacteria pose a sustained burden to human health. Most famously, Mycobacterium tuberculosis causes the human disease, tuberculosis. However, other environmental mycobacteria also cause chronic and acute human disease. This burden of infection and disease is in part due to a lack of a viable vaccine that protects adults from pulmonary tuberculosis. To develop the vaccines and therapeutics needed to control mycobacterial disease, we need a better understanding of mycobacterial biology and the mechanisms it uses to cause disease.

A key mechanism that bacteria use to promote their survival is by the targeted transport of bacterial proteins, small molecules or nucleic acids directly into the host (secretion). In the host these molecules directly interact with and disrupt the function of cellular processes which are required for identifying and eliminating the bacteria. Targeted protein secretion is used by several successful bacterial pathogens, including M. tuberculosis, to transport proteins to distinct cellular locations. Through a better understanding of protein transport systems and the proteins they transport we will gain important insight into how mycobacteria interact with the host and cause disease. The long-term goal of my research program is to define the molecular mechanisms underlying mycobacterial pathogenesis. To address this goal, our current research is focused on identifying novel genes and mechanisms required for and regulating mycobacterial protein transport. We expect that this course of research will not only expand our understanding M. tuberculosis biology, but may also lead to the identification of novel targets for anti-virulence based therapeutics against TB.

We use an interdisciplinary approach to study mycobacterial pathogenesis. We use genetics and molecular biology to study M. tuberculosis and the non-tubercular pathogen, Mycobacterium marinum. M. marinum is an established model for several aspects of mycobacterial pathogenesis. To complement our genetic approaches, we use proteomics, transcriptomics and biochemistry.

Our current research is focused on identifying protein substrates secreted by mycobacterial Type VII secretion systems, with a specific focus on ESX-1. We are defining how ESX-1 substrates function to promote mycobacterial virulence, through the regulation of gene expression and as effector proteins within the host cell. Finally, we are interested in how modification of mycobacterial proteins promotes virulence.  

 

 

Biography:

  • Associate Professor, University of Notre Dame, IN 2015-Present
  • Assistant Professor, University of Notre Dame, IN 2009-2015
  • Postdoctoral Fellow, University of California San Francisco, CA 2003-2009
  • PhD. in Molecular Biology, Princeton University, NJ 2003
  • B.S. in Biological Sciences, Carnegie Mellon University, PA 1998

 

Recent Papers:

  • Chirakos, A.E., Nicholson, K.R., Huffman, A. and Champion PA Conserved dual functionality of EspE and EspF substrates in ESX-1-mediated lysis and gene expression. Infection and Immunity, 2020 Sep 8;IAI.00289-20.doi: 10.1128/IAI.00289-20. PMID: 32900815
  • Chirakos, A.E., Balaram, A., Conrad, W & Champion P.A. (2020) Modeling tubercular ESX-1 secretion using Mycobacterium marinum. Microbiology and Molecular Biology Reviews, Invited Review. 2020 Sep 2;84(4):e00082-19. doi: 10.1128/MMBR.00082-19. Print 2020 Nov 18. PMID: 32878966
  • Sanchez KG, Ferrell MJ, Chirakos AE, Nicholson KR, Abramovitch RB, Champion MM, Champion PA. EspM Is a Conserved Transcription Factor That Regulates Gene Expression in Response to the ESX-1 System. mBio. 2020 Feb 4;11(1):e02807-19. doi: 10.1128/mBio.02807-19.  PMID: 32019792
  • Bosserman RE, Nicholson KR, Champion MM, Champion PA. A New ESX-1 Substrate in Mycobacterium marinum That Is Required for Hemolysis but Not Host Cell Lysis. J Bacteriol. 2019 Jun 21;201(14):e00760-18. doi: 10.1128/JB.00760-18. Print 2019 Jul 15.PMID: 30833360
  • Thompson CR, Champion MM, Champion PA. Quantitative N-Terminal Footprinting of Pathogenic Mycobacteria Reveals Differential Protein Acetylation. J Proteome Res. 2018 Sep 7;17(9):3246-3258. doi: 10.1021/acs.jproteome.8b00373. Epub 2018 Aug 16.PMID: 30080413  
  • Bosserman RE, Thompson CR, Nicholson KR, Champion PA. 2018. Esx paralogs are functionally equivalent to ESX-1 proteins but are dispensable for virulence in Mycobacterium marinum. J Bacteriol 200:e00726-17. https://doi.org/10.1128/JB.00726-17.
  • Bosserman RE, Nguyen TT, Sanchez KG, Chirakos EA, Ferrell MJ, Thompson CR, Champion MM, Abramovitch RB, and Champion PA. WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum. PNAS, 2017; doi:10.1073/pnas.1710167114