Melanie Cushion, PhD
Int Med-Infect Disease
Professor
VAMC B412
3200 Vine St
Cincinnati OH 45267
(513)558-4704
Research Summary

Pneumocystis carinii organisms are eukaryotic protistan pathogens that can be detected in a wide variety of mammalian lungs. In immunocompromised hosts, especially those patients with AIDS, P. carinii are able to cause a pneumonia which remains a major source of morbidity and mortality. Diagnosis, drug screening, and almost every aspect of P.carinii research has been hindered by the lack of a continuous in vitro cultivation system for these organisms. The mode of transmission and the life cycle of this group of pathogens has not been defined. The research in Dr. Melanie Cushion’s laboratory is centered on understanding the basic biological processes and the natural history of infection as a strategy for its control and treatment. There are 3 areas of study:

  1. Molecular characterization of P.carinii and analyses of organism population dynamics in infected hosts;
  2. Definition of organism metabolism for exploitation as drug targets;
  3. Sequencing and mapping of the genomes of Pneumocystis from rat, human and mouse for: syntenic comparisons; understanding their basic biological processes; development of novel drug targets; and evolution of these pathogens.

In the first approach, molecular techniques such as electrophoretic karyotyping, polymerase chain reaction, gene sequencing and southern hybridization are used to characterize P. carinii populations in infected animal colonies, analyze the stability of the infecting population, and assess the compatibilities of these characterized isolates.

In the second approach, measurement of cellular ATP using a bioluminescent technique is used to assess the nutritional requirements of P. carinii ex vivo and to investigate the mechanisms of therapeutic modalities.

In the third approach, structural genomics and informatic analysis of sequence data will be used to predict metabolic pathways and create the reagents for microarray analysis.

Dr. Cushion is a prominent investigator in the basic biology of P. carinii. Her research interests include in vitro cultivation, life cycle, drug susceptibility testing, transmission of the organism and genomics. She recently received a Research Career Scientist Award from the Veterans Administration in recognition of her research and service. Dr. Cushion was recently appointed as the Associate Chair for Research for the Department of Internal Medicine. Her published works include over 100 original publications and over 100 abstracts and presented papers. She currently serves as an associate editor for The Journal of Eukaryotic Microbiology and as ad hoc reviewer for Journal of Clinical Microbiology, Infection and Immunity, and the Journal of Infectious Diseases. Dr. Cushion has been elected to membership in the Genetics Society of America, Society of Protistology, and the American Society for Microbiology. She directs the Pneumocystis Genome Project which can be viewed at: http://pneumocystis.cchmc.org

Selected Publications
Cushion MT, Walzer PD. Preclinical drug discovery for new anti-pneumocystiscompounds. Curr Med Chem. 2009;16(20):2514-30. PubMed PMID: 19601796.
Brubaker R, Redhead SA, Stringer JR, Keely SP, Cushion MT. Misinformationabout Pneumocystis. Clin Exp Dermatol. 2009 Jun 25. [Epub ahead of print] PubMed
Phylogenomic analyses support the monophyly of Taphrinomycotina, including Schizosaccharomyces fission yeast Liu Y, Leigh JW, Brinkmann H, Cushion MT, Rodriguez-Ezpeleta N, Philippe H, Lang BF.Mol Biol Evol. 2009 Jan;26(1):27-34. Epub 2008 Oct 14.PMID: 18922765 [PubMed - indexed for MEDLINE]
Cushion MT, Collins MS, Linke MJ. Biofilm formation by Pneumocystis spp.Eukaryot Cell. 2009 Feb;8(2):197-206. Epub 2008 Sep 26. PubMed PMID: 18820078;PubMed Central PMCID: PMC2643605.
Cushion MT, Smulian AG, Slaven BE, Sesterhenn T, Arnold J, Staben C, PorolloA, Adamczak R, Meller J. Transcriptome of Pneumocystis carinii during fulminateinfection: carbohydrate metabolism and the concept of a compatible parasite. PLoSOne. 2007 May 9;2(5):e423. PubMed PMID: 17487271; PubMed Central PMCID:PMC1855432.
Pneumocystis and Trypanosoma cruzi: nomenclature and typifications.Redhead SA, Cushion MT, Frenkel JK, Stringer JR.J Eukaryot Microbiol. 2006 Jan-Feb;53(1):2-11. Review.PMID: 16441572 [PubMed - indexed for MEDLINE]