null Donald Sheppard, MD
medical mycology • aspergillus • biofilms • host-pathogen interactions
My research focuses on understanding how molds and other fungi cause human disease. Recently, our laboratory discovered that fungi secrete sugars that can act as a glue in order to help fungi attach to human lung cells and hide from the immune system during lung infections. My research focuses on fungi that infect humans. In particular, we focus on the common mold Aspergillus fumigatus, which causes pneumonia in patients who have received chemotherapy, organ transplantation, bone marrow transplantation or high dose cortisone therapy. Despite the use of current antifungal drugs, this pneumonia is fatal for more than half the affected patients. Our group is working to identify how this fungus invades human tissues in order to develop new, more effective antifungal therapies to prevent and cure this aggressive and common condition.
Snarr BD, St-Pierre G, Ralph B, Lehous M, Sato Y, Rancourt A, Takazono T, Baistrocchi SR, Corsini R, Cheng MP, Sugrue M, Baden LR, Izumikawa Km Mukae H, Wingard JR, King IL, Divangahi M, Satoh MS, Yipp BG, Sato S, Sheppard DC. Galectin-3 enhances neutrophil motility and extravasation into the airways during Aspergillus fumigatus infection. PLOS Pathogens, 2020 Aug 4;16(8):e1008741. doi: 10.1371/journal.ppat.1008741. PMID: 32750085.
Bamford, N.C., Le Mauff, F., Van Loon, J.C. et al. Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation. Nat Commun 11, 2450 (2020).
Stewart JIP, Fava VM, Kerkaert JD, Subramanian AS, Gravelat FN, Lehoux M, Howell PL, Cramer RA, Sheppard DC. Reducing Aspergillus fumigatus Virulence through Targeted Dysregulation of the Conidiation Pathway. mBio. 2020 Feb 4;11(1). pii: e03202-19. doi: 10.1128/mBio.03202-19.
Le Mauff F, Bamford NC, Alnabelseya N, Zhang Y, Baker P, Robinson H, Codée JDC, Howell PL, Sheppard DC. Molecular mechanism of Aspergillus fumigatus biofilm disruption by fungal and bacterial glycoside hydrolases. J Biol Chem. 2019 Jul 12;294(28):10760-10772. doi: 10.1074/jbc.RA119.008511.
Snarr BD, Baker P, Bamford NC, Sato Y, Liu H, Lehoux M, Gravelat FN, Ostapska H, Baistrocchi SR, Cerone RP, Filler EE, Parsek MR, Filler SG, Howell PL, and Sheppard DC. (2017) Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity. PNAS Jul 3;114(27):7124-7129. doi: 10.1073/pnas.1702798114