Felipe H. Santiago-Tirado Assistant Professor

The Cell Biology of Cryptococcal Disease
Felipe H. Santiago-Tirado

Research Interests:

Fungal infections are an underappreciated global public health crisis, with over 300 million people globally afflicted with serious fungal infections, and 25 million of them at risk of dying or suffering life-long sequelae (http://www.gaffi.org/why/fungal-disease-frequency/). These infections are among the most difficult to treat diseases, not only due to a lack of effective antifungals, but also due to an incomplete understanding of their pathogenesis, resulting in 1.6 million deaths yearly. The most common culprit is the ubiquitous environmental fungus Cryptococcus neoformans, which was responsible for 200,000 deaths in 2016. This fungus is inhaled into the lung environment, where it is quickly taken up by host phagocytes. In these phagocytes, the cryptococcal cells are able to not only survive, but proliferate and disseminate, eventually causing a deadly meningoencephalitis after crossing the blood-brain barrier. My primary research goals are to understand how C. neoformans can survive inside host phagocytes and cross cellular barriers, which are the main drivers of disease progression. I am also interested in the unique cell biology of this fungus, such as its ability to secrete a polysaccharide capsule, offering the potential of novel therapeutic targets, as well as uncover basic biology applicable to other pathogens.

 

Biography:

  • Assistant Professor, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN  2018 – Present
  • Staff Research Scientist, Molecular Microbiology Department, Washington University School of Medicine, St. Louis, MO  2017 – 2018
  • Marine Biological Laboratory (MBL) Advanced Course, Molecular Mycology: Current Approaches to Fungal Pathogenesis, MBL, Woods Hole, MA  2013
  • Postdoctoral Researcher, Molecular Microbiology Department, Washington University School of Medicine, St. Louis, MO 2012 – 2017
  • Postdoctoral Researcher, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 2011 – 2012
  • PhD, Molecular and Cellular Biology, Cornell University, Ithaca, NY  2011

 

Selected Publications:

  • Santiago-Tirado FH, Hurtaux T, Geddes-McAlister J, Nguyen D, Helms V, Doering TL, and Römisch K. (2022) The ER protein translocation channel subunit Sbh1 controls virulence of Cryptococcus neoformans. Cellular Microbiology, In press, 28 Sep 2022.
  • Santiago-Burgos EJ, Stuckey PV, Santiago-Tirado FH. (2022) Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way. Frontiers in Cellular and Infectious Microbiology, 12:967486. doi: 10.3389/fcimb.2022.967486.
  • Winski CJ, Qian Y, Mobashery S, Santiago-Tirado FH. (2022) An Atypical ABC Transporter Is Involved in Antifungal Resistance and Host Interactions in the Pathogenic Fungus Cryptococcus neoformans. mBio, 13(4):e0153922. doi: 10.1128/mbio.01539-22.
  • Santiago-Tirado FH. (2019) mSphere of Influence: the Power of Yeast Genetics Still Going Strong! mSphere. 4(5). doi: 10.1128/mSphere.00647-19.
  • Santiago-Tirado FH, Klein RS, and Doering TL. (2019) An In Vitro Brain Endothelial Model for Studies of Cryptococcal Transmigration into the Central Nervous System. Curr Protoc Microbiol. 53(1):e78. doi: 10.1002/cpmc.78.
  • Santiago-Tirado, F.H., Onken, M.D., Klein, R.S., Cooper, J.A., and Doering, T.L. (2017) Trojan horse transit contributes to blood-brain barrier crossing of a eukaryotic pathogen. mBio 8 (1): e02183-16. doi: 10.1128/mBio.02183-16
  • Santiago-Tirado, F.H. and Doering, T.L. (2017) False friends: Phagocytes as Trojan horses in microbial brain infections. PLoS Pathogens 13(12): e1006680. doi: 10.1371/journal.ppat.1006680
  • Santiago-Tirado, F.H. and Doering, T.L. (2016) All about that fat: Lipid modification of proteins in Cryptococcus neoformansJournal of Microbiology 54: 212-222. doi: 10.1007/s12275-016-5626-6
  • Santiago-Tirado, F.H., Peng, T., Yang, M., Hang, H.C., and Doering, T.L. (2015) A Single Protein S-acyl Transferase Acts through Diverse Substrates to Determine Cryptococcal Morphology, Stress Tolerance, and Pathogenic Outcome. PLoS Pathogens 11: e1004908. doi: 10.1371/journal.ppat.1004908
  • Chernyakov, I., Santiago-Tirado, F., and Bretscher, A. (2013) Active segregation of yeast mitochondria by Myo2 is essential and mediated by Mmr1 and Ypt11. Current Biology 23, 1818-1824. doi: 10.1016/j.cub.2013.07.053
  • Santiago-Tirado, F.H., Legesse-Miller, A., Schott, D., and Bretscher, A. (2011) PI4P and Rab inputs collaborate in myosin-V-dependent transport of secretory compartments in yeast. Developmental Cell 20: 47-59. doi: 10.1016/j.devcel.2010.11.006