Cressida Madigan

Research

My lab uses genetic and imaging tools to study mechanisms of infection-mediated inflammation and neurological injury. We use zebrafish as a model host, which allows for real-time observation of infections that typically play out at difficult-to-access sites in humans. We are currently focused on understanding how the mycobacteria that cause leprosy and tuberculosis instigate neurological injury. In leprosy, this nerve damage and inflammation contributes to the stigmatizing deformities that patients endure, such as blindness and loss of fingers. In tuberculosis, central nervous system infection is the deadliest form of TB, and is most common in children under 5 or in HIV-positive adults. By observing mycobacterial infection of the zebrafish brain, we hope to identify pathways of central nervous system inflammation that can be targeted by host-directed therapies. Many of the pathogens we study have caused significant epidemics in human history or are diseases of poverty, and are therefore under-studied.

Publications

  • Madigan CA, Cambier CJ, Kelly-Scumpia KM, Scumpia PO, Cheng TY, Zailaa J, Bloom BR, Moody DB, Smale ST, Sagasti A, Modlin RL, Ramakrishnan L. (2017) A macrophage response to Mycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy. Cell. 170(5):973-985. e10. doi: 10.1016/j.cell.2017.07.030
  • Madigan CA, Cameron J, Ramakrishnan L. (2017) A zebrafish model for Mycobacterium leprae granulomatous infection. Journal of Infectious Diseases, doi: 10.1093/infdis/jix329
  • Inkeles MS, Teles RM, Pouldar D, Andrade PR, Madigan CA, Lopez D, Ambrose M, Noursadeghi M, Sarno EN, Rea TH, Ochoa MT, Iruela-Arispe ML, Ottenhoff TH, Geluk A, Bloom BR, Modlin RL. (2016) Cell-type deconvolution with immune response pathways identifies gene networks of host defense and immunopathology in leprosy. Journal of Clinical Investigation Insight. 1(15):e88843.
  • Madigan CA, Martinot AJ, Wei J-R, Madduri A, Cheng T-Y, Young DC, Layre E, Murry JP, Rubin EJ, Moody DB. (2015) Mycobactin Synthase K links iron, lipid homeostasis, and virulence in M. tuberculosis. PLoS Pathogens. 11(3):e1004792.
  • Madigan CA, Cheng TY, Young DC, Layre E, McConnell MJ, Debono CA, Murry JP, Wei JR, Barry CE 3rd, Rodriguez GM, Matsunaga I, Rubin EJ, Moody DB. (2012) Lipidomic discovery of deoxysiderophores reveals a revised pathway of mycobactin biosynthesis in M. tuberculosis. Proceedings of the National Academy of Science. 109(4):1257-62
  • Layre E, Sweet L, Hong S, Madigan CA, Desjardins D, Young DC, Cheng TY, Annand JW, Kim K, Shamputa IC, McConnell MJ, Debono CA, Behar SM, Minnaard AJ, Murray M, Barry CE 3rd, Matsunaga I, Moody DB. (2011) A Comparative Lipidomics Platform for Chemotaxonomic Analysis of Mycobacterium tuberculosis. Chemistry & Biology. 18(12): 1537-49
  • Huang S, Cheng TY, Young DC, Layre E, Madigan CA, Shires J, Cerundolo V, Altman JD, Moody DB. (2011) Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. Proceedings of the National Academy of Science 108(48): 19335-40.
  • Molofsky AB, Byrne BG, Whitfield NN, Madigan CA, Fuse ET, Tateda K, Swanson MS. (2006) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. Journal of Experimental Medicine. 203(4): 1093-104.