Don 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.
Gravelat FN, Beauvais A, Liu H, Lee MJ, Snarr BD, Chen D, Xu W, Kravtsov I, Hoareau CM, Vanier G, Urb M, Campoli P, Al Abdallah Q, Lehoux M, Chabot JC, Ouimet MC, Baptista SD, Fritz JH, Nierman WC, Latgé JP, Mitchell AP, Filler SG, Fontaine T, Sheppard DC. Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system. PLoS Pathog. 2013;9(8):e1003575. doi: 10.1371/journal.ppat.1003575. Epub 2013 Aug 22. PMID: 23990787.
Urb M, Snarr BD, Wojewodka G, Lehoux M, Lee MJ, Ralph B, Divangahi M, King IL, McGovern TK, Martin JG, Fraser R, Radzioch D, Sheppard DC. The evolution of the immune response to chronic airway colonization with Aspergillus fumigatus hyphae. Infect Immun. 2015 Jun 29. pii: IAI.00359-15. [Epub ahead of print] PMID: 26123803.
Lee MJ, Gravelat FN, Cerone RP, Baptista SD, Campoli PV, Choe SI, Kravtsov I, Vinogradov E, Creuzenet C, Liu H, Berghuis AM, Latgé JP, Filler SG, Fontaine T, Sheppard DC. Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides. J Biol Chem. 2014 Jan 17;289(3):1243-56. doi: 10.1074/jbc.M113.522516. Epub 2013 Nov 20. PMID: 24257745.
Campoli P, Perlin DS, Kristof AS, White TC, Filler SG, Sheppard DC. Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis. J Infect Dis. 2013 Nov 15;208(10):1717-28. doi: 10.1093/infdis/jit358. Epub 2013 Aug 1. PMID: 23908482.
Sheppard DC, Filler SG. Host cell invasion by medically important fungi. Cold Spring Harb Perspect Med. 2014 Nov 3;5(1):a019687. doi: 10.1101/cshperspect.a019687. PMID: 25367974.