Durham, NC 27710
Immunocompromised pediatric patients, especially children with invasive fungal infections
Our laboratory focuses on studying the molecular pathogenesis of Aspergillus fumigatus, the leading infectious killer in immunocompromised patients with cancer or following transplantation. All of our work is very translational in nature – all of it is performed with the specific goal of directly improving our fundamental understanding of how and why this organism is so deadly and how to best prevent and treat it. Our laboratory uses molecular genetics to knock-out pathogenesis genes and analyze their function and role in disease, including microarray, real-time PCR, proteomics, and biochemical approaches. We also perform extensive in vitro testing of both antifungal compounds and genetic screens. Since we are focused on the pathogenesis, we utilize numerous different animal models specifically designed to mimic the immune system of a cancer patient or transplant recipient.
Currently we are focused on the calcineurin cell signaling pathway as a model for studying pathogenesis – both as a stress response and as a mechanism for defeating disease establishment and progression. We have knocked out numerous genes in the calcineurin pathway and have performed extensive analyses on their functions leading to several exciting results with real implications for advanced clinical management. Several of the mutants in the calcineurin pathway are defective in cell wall structure, which has led us to perform detailed investigations of the cell wall components and propose novel ideas regarding how to further destroy this deadly fungus.
I am also a leader in several clinical trials for invasive aspergillosis management, linking nicely with the scientific work to marry the clinical and scientific arenas. I have been the co-chair of all five of the international Advances Against Aspergillosis conferences, most recently in Istanbul (www.AAA2012.org), as well as co-chair of the 2nd International Fungal Cell Wall meeting, most recently in France. I am the co-editor of the largest textbook in the field, Aspergillus fumigatus and Aspergillosis (ASM Press, 2009).
This faculty member has no reported relationships with industry.
Steinbach, WJ; Cramer, RA; Perfect, BZ; Asfaw, YG; Sauer, TC; Najvar, LK; Kirkpatrick, WR; Patterson, TF; Benjamin, DK; Heitman, J; Perfect, JR. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryotic Cell. 2006;5:1091-1103. (2006) Abstract
Zaoutis, TE; Heydon, K; Chu, JH; Walsh, TJ; Steinbach, WJ. Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000. Pediatrics. 2006;117:e711-e716. (2006) Abstract
Steinbach, WJ; Benjamin, DK; Kontoyiannis, DP; Perfect, JR; Lutsar, I; Marr, KA; Lionakis, MS; Torres, HA; Jafri, H; Walsh, TJ. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clinical Infectious Diseases. 2004;39:192-198. (2004) Abstract
Steinbach, WJ; Benjamin, DK; Trasi, SA; Miller, JL; Schell, WA; Zaas, AK; Foster, WM; Perfect, JR. Value of an inhalational model of invasive aspergillosis. Medical Mycology. 2004;42:417-425. (2004) Abstract
Steinbach, WJ; Schell, WA; Blankenship, JR; Onyewu, C; Heitman, J; Perfect, JR. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy. 2004;48:1664-1669. (2004) Abstract
Steinbach, WJ; Singh, N; Miller, JL; Benjamin, DK; Schell, WA; Heitman, J; Perfect, JR. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus isolates from transplant and nontransplant patients. Antimicrobial Agents and Chemotherapy. 2004;48:4922-4925. (2004) Abstract