Bloodstream infections due to Candida species are encountered with an increasing frequency in clinical practice, leading to significant morbidity and mortality. This project will involve the unprecedented study of over 700 patients to systematically evaluate select factors associated with outcomes among patients with fungemia due to albicans and non-albicans Candida spp. This will result in the largest collection of data worldwide investigating host-response relationships among patients with candidemia, and involve both retrospective and prospective investigations. The project will enable the candidate, Melissa Johnson, to learn the skills necessary to become a successful clinician-scientist. She is a member of the Duke University Mycology Research Unit, which has a long and rich tradition of excellence in investigation of basic and clinical mycology. Together with her mentor, John R. Perfect, and supported by the resources of the Department of Medicine at Duke University Medical Center, she will develop a model for risk- assessment and an evidence-based treatment approach for patients with fungemia due to Candida spp. She will also evaluate the role of select pharmacodynamic, immunogenomic, and pharmacogenomic factors in associated clinical outcomes in candidemic patients. This award will enable the candidate to build upon her experiences as a clinician and researcher and obtain the skills critical for success as an independent investigator. Project activities will strengthen the candidate's technical abilities through exposure to a variety of laboratory techniques. She will also learn the various facets of epidemiologic methods, study design, mathematical modeling, and statistical analysis through interaction with her collaborators and project advisors. In addition, she will complement project activities with graduate-level coursework in pharmacokinetic and pharmacodynamic modeling at University of North Carolina and statistics, epidemiology, and clinical research as she completes the Master of Science in Clinical Research at Duke.
| Smeekens, S P; Malireddi, R K; Plantinga, T S et al. (2014) Autophagy is redundant for the host defense against systemic Candida albicans infections. Eur J Clin Microbiol Infect Dis 33:711-22 |
| Kumar, Vinod; Cheng, Shih-Chin; Johnson, Melissa D et al. (2014) Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia. Nat Commun 5:4675 |
| Rosentul, Diana C; Plantinga, Theo S; Farcas, Marius et al. (2014) Role of autophagy genetic variants for the risk of Candida infections. Med Mycol 52:333-41 |
| Lionakis, Michail S; Swamydas, Muthulekha; Fischer, Brett G et al. (2013) CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J Clin Invest 123:5035-51 |
| Rosentul, D C; Plantinga, T S; Scott, W K et al. (2012) The impact of caspase-12 on susceptibility to candidemia. Eur J Clin Microbiol Infect Dis 31:277-80 |
| Plantinga, Theo S; Johnson, Melissa D; Scott, William K et al. (2012) Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis 205:934-43 |
| Johnson, Melissa D; Plantinga, Theo S; van de Vosse, Esther et al. (2012) Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis 54:502-10 |
| Plantinga, Theo S; Johnson, Melissa D; Scott, William K et al. (2012) Human genetic susceptibility to Candida infections. Med Mycol 50:785-94 |
| Rosentul, Diana C; Plantinga, Theo S; Oosting, Marije et al. (2011) Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 204:1138-45 |
| Johnson, Melissa D; Perfect, John R (2010) Use of Antifungal Combination Therapy: Agents, Order, and Timing. Curr Fungal Infect Rep 4:87-95 |
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