Dena L. Toffaletti | Scholars@Duke

Dena L. Toffaletti
Associate Professor in Medicine

As an investigator in John Perfect's laboratory, I have continued to study the molecular pathogenesis of Cryptococcus neoformans. We are interested in identifying virulence genes expressed by the fungus during infection using our rabbit model of cryptococcal meningitis and during in vitro exposure to the pathological temperature of 37 degrees C. By PCR differential display, we are identifying genes associated with pathogenesis of the organism and assessing their effects at the molecular level using a 2-hybrid system. In addition, we are disrupting targeted virulence genes using biolistic transformation and assessing their role in the virulence of C neoformans in rabbit and murine models of cryptococcal disease.

Key words: Cryptococcus neoformans
Virulence
Molecular Pathogenesis
Transformation

Current Appointments & Affiliations

Associate Professor in Medicine, Medicine, Infectious Diseases, Medicine 2010

Contact Information

337 Sands Bldg, Research Drive, Durham, NC 27710
Duke Box 3138, Durham, NC 27710
toffa001@mc.duke.edu (919) 681-6276

Background
Education, Training, & Certifications
- Fellow, Microbiology And Immunology, Duke University School of Medicine 1979 - 1981
- Fellow, Pathology, University of Connecticut School of Medicine 1977 - 1979
- Ph.D., University of North Carolina at Chapel Hill 1977
Duke Appointment History
- Assistant Professor in Medicine, Medicine, Infectious Diseases, Medicine 2006 - 2010
- Assistant Research Professor in Medicine, Medicine, Infectious Diseases, Medicine 1994 - 2006
Research
Selected Grants
- Pathobiology of C. neoformans in the Central Nervous System awarded by National Institutes of Health 2007 - 2019
- Molecular Umbrella-Amphotericin B Conjugates awarded by Lehigh University 2012 - 2016
- Genetic molecular biology of virulence in C. neoformans awarded by National Institutes of Health 1991 - 2008
Publications & Artistic Works
Selected Publications
- Journal Articles
  - Miao, Y, Tenor, JL, Toffaletti, DL, Maskarinec, SA, Liu, J, Lee, RE, Perfect, JR, and Brennan, RG. "Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design." mBio 8, no. 4 (July 25, 2017). Full Text
  - Homer, CM, Summers, DK, Goranov, AI, Clarke, SC, Wiesner, DL, Diedrich, JK, Moresco, JJ, Toffaletti, D, Upadhya, R, Caradonna, I, Petnic, S, Pessino, V, Cuomo, CA, Lodge, JK, Perfect, J, Yates, JR, Nielsen, K, Craik, CS, and Madhani, HD. "Intracellular Action of a Secreted Peptide Required for Fungal Virulence." Cell host & microbe 19, no. 6 (June 2016): 849-864. Full Text
  - Chen, Y, Toffaletti, DL, Tenor, JL, Litvintseva, AP, Fang, C, Mitchell, TG, McDonald, TR, Nielsen, K, Boulware, DR, Bicanic, T, and Perfect, JR. "The Cryptococcus neoformans transcriptome at the site of human meningitis." mBio 5, no. 1 (February 4, 2014): e01087-e01013. Full Text Open Access Copy
  - Chen, Y, Toffaletti, DL, Tenor, JL, Litvintseva, AP, Fang, C, Mitchell, TG, McDonald, TR, Nielsen, K, Boulware, DR, Bicanic, T, and Perfect, JR. "The Cryptococcus neoformans transcriptome at the site of human meningitis." mBio 5, no. 1 (February 4, 2014). Full Text
  - Frazzitta, AE, Vora, H, Price, MS, Tenor, JL, Betancourt-Quiroz, M, Toffaletti, DL, Cheng, N, and Perfect, JR. "Nitrogen source-dependent capsule induction in human-pathogenic cryptococcus species." Eukaryot Cell 12, no. 11 (November 2013): 1439-1450. Full Text Link to Item
  - Liu, T-B, Kim, J-C, Wang, Y, Toffaletti, DL, Eugenin, E, Perfect, JR, Kim, KJ, and Xue, C. "Brain inositol is a novel stimulator for promoting Cryptococcus penetration of the blood-brain barrier." PLoS Pathog 9, no. 4 (2013): e1003247-. Full Text Link to Item
  - He, X, Lyons, DM, Toffaletti, DL, Wang, F, Qiu, Y, Davis, MJ, Meister, DL, Dayrit, JK, Lee, A, Osterholzer, JJ, Perfect, JR, and Olszewski, MA. "Virulence factors identified by Cryptococcus neoformans mutant screen differentially modulate lung immune responses and brain dissemination." Am J Pathol 181, no. 4 (October 2012): 1356-1366. Full Text Link to Item
  - Fang, W, Price, MS, Toffaletti, DL, Tenor, J, Betancourt-Quiroz, M, Price, JL, Pan, W-H, Liao, W-Q, and Perfect, JR. "Pleiotropic effects of deubiquitinating enzyme Ubp5 on growth and pathogenesis of Cryptococcus neoformans." PLoS One 7, no. 6 (2012): e38326-. Full Text Link to Item
  - Tseng, H-K, Liu, C-P, Price, MS, Jong, AY, Chang, J-C, Toffaletti, DL, Betancourt-Quiroz, M, Frazzitta, AE, Cho, W-L, and Perfect, JR. "Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system." PLoS One 7, no. 9 (2012): e45083-. Full Text Link to Item
  - Price, MS, Betancourt-Quiroz, M, Price, JL, Toffaletti, DL, Vora, H, Hu, G, Kronstad, JW, and Perfect, JR. "Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host. (Published online)" MBio 2, no. 3 (2011): e00103-e00111. Full Text Link to Item
  - Price, MS, Betancourt-Quiroz, M, Price, JL, Toffaletti, DL, Vora, H, Hu, G, Kronstad, JW, and Perfect, JR. "Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host." mBio 2, no. 3 (2011): e00103-e00111. Full Text
  - Lee, A, Toffaletti, DL, Tenor, J, Soderblom, EJ, Thompson, JW, Moseley, MA, Price, M, and Perfect, JR. "Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis." Infection and immunity 78, no. 10 (October 2010): 4213-4225. Full Text
  - Ngamskulrungroj, P, Himmelreich, U, Breger, JA, Wilson, C, Chayakulkeeree, M, Krockenberger, MB, Malik, R, Daniel, H-M, Toffaletti, D, Djordjevic, JT, Mylonakis, E, Meyer, W, and Perfect, JR. "The trehalose synthesis pathway is an integral part of the virulence composite for Cryptococcus gattii." Infect Immun 77, no. 10 (October 2009): 4584-4596. Full Text Link to Item
  - Chayakulkeeree, M, Rude, TH, Toffaletti, DL, and Perfect, JR. "Fatty acid synthesis is essential for survival of Cryptococcus neoformans and a potential fungicidal target." Antimicrob Agents Chemother 51, no. 10 (October 2007): 3537-3545. Full Text Link to Item
  - Petzold, EW, Himmelreich, U, Mylonakis, E, Rude, T, Toffaletti, D, Cox, GM, Miller, JL, and Perfect, JR. "Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans." Infect Immun 74, no. 10 (October 2006): 5877-5887. Full Text Link to Item
  - Toffaletti, DL, Nielsen, K, Dietrich, F, Heitman, J, and Perfect, JR. "Cryptococcus neoformans mitochondrial genomes from serotype A and D strains do not influence virulence." Curr Genet 46, no. 4 (October 2004): 193-204. Full Text Link to Item
  - Miller, JL, Schell, WA, Wills, EA, Toffaletti, DL, Boyce, M, Benjamin, DK, Bartroli, J, and Perfect, JR. "In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans." Antimicrob Agents Chemother 48, no. 2 (February 2004): 384-387. Link to Item
  - Steen, BR, Zuyderduyn, S, Toffaletti, DL, Marra, M, Jones, SJM, Perfect, JR, and Kronstad, J. "Cryptococcus neoformans gene expression during experimental cryptococcal meningitis." Eukaryot Cell 2, no. 6 (December 2003): 1336-1349. Link to Item
  - Luberto, C, Martinez-Mariño, B, Taraskiewicz, D, Bolaños, B, Chitano, P, Toffaletti, DL, Cox, GM, Perfect, JR, Hannun, YA, Balish, E, and Del Poeta, M. "Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans." J Clin Invest 112, no. 7 (October 2003): 1080-1094. Full Text Link to Item
  - Nielsen, K, Cox, GM, Wang, P, Toffaletti, DL, Perfect, JR, and Heitman, J. "Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates." Infect Immun 71, no. 9 (September 2003): 4831-4841. Link to Item
  - Toffaletti, DL, Del Poeta, M, Rude, TH, Dietrich, F, and Perfect, JR. "Regulation of cytochrome c oxidase subunit 1 (COX1) expression in Cryptococcus neoformans by temperature and host environment." Microbiology 149, no. Pt 4 (April 2003): 1041-1049. Full Text Link to Item
  - Toffaletti, DL, Poeta, MD, Rude, TH, Dietrich, F, and Perfect, JR. "Regulation of cytochrome c oxidase subunit 1 (COX1) expression in Cryptococcus neoformans by temperature and host environment." Microbiology 149, no. 4 (2003): 1041-1049. Full Text
  - Rude, TH, Toffaletti, DL, Cox, GM, and Perfect, JR. "Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans." Infect Immun 70, no. 10 (October 2002): 5684-5694. Link to Item
  - Luberto, C, Toffaletti, DL, Wills, EA, Tucker, SC, Casadevall, A, Perfect, JR, Hannun, YA, and Del Poeta, M. "Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans." Genes Dev 15, no. 2 (January 15, 2001): 201-212. Link to Item
  - Del Poeta, M, Toffaletti, DL, Rude, TH, Dykstra, CC, Heitman, J, and Perfect, JR. "Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target." Genetics 152, no. 1 (May 1999): 167-178. Link to Item
  - del Poeta, M, Toffaletti, DL, Rude, TH, Sparks, SD, Heitman, J, and Perfect, JR. "Cryptococcus neoformans differential gene expression detected in vitro and in vivo with green fluorescent protein." Infect Immun 67, no. 4 (April 1999): 1812-1820. Link to Item
  - Thompson, JR, Douglas, CM, Li, W, Jue, CK, Pramanik, B, Yuan, X, Rude, TH, Toffaletti, DL, Perfect, JR, and Kurtz, M. "A glucan synthase FKS1 homolog in cryptococcus neoformans is single copy and encodes an essential function." J Bacteriol 181, no. 2 (January 1999): 444-453. Link to Item
  - Firestine, SM, Misialek, S, Toffaletti, DL, Klem, TJ, Perfect, JR, and Davisson, VJ. "Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis." Arch Biochem Biophys 351, no. 1 (March 1, 1998): 123-134. Full Text Link to Item
  - Toffaletti, DL, and Perfect, JR. "Study of Cryptococcus neoformans actin gene regulation with a beta-galactosidase-actin fusion." J Med Vet Mycol 35, no. 5 (September 1997): 313-320. Link to Item
  - Odom, A, Muir, S, Lim, E, Toffaletti, DL, Perfect, J, and Heitman, J. "Calcineurin is required for virulence of Cryptococcus neoformans." EMBO J 16, no. 10 (May 15, 1997): 2576-2589. Full Text Link to Item
  - Toffaletti, DL, and Perfect, JR. "Study of Cryptococcus neoformans actin gene regulation with a β-galactosidase-actin fusion." Journal of Medical and Veterinary Mycology 35, no. 5 (1997): 313-320.
  - Cox, GM, Toffaletti, DL, and Perfect, JR. "Dominant selection system for use in Cryptococcus neoformans." J Med Vet Mycol 34, no. 6 (November 1996): 385-391. Link to Item
  - Cox, GM, Toffaletti, DL, and Perfect, JR. "Dominant selection system for use in Cryptococcus neoformans." Journal of Medical and Veterinary Mycology 34, no. 6 (1996): 385-391.
  - Lodge, JK, Jackson-Machelski, E, Toffaletti, DL, Perfect, JR, and Gordon, JI. "Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans." Proc Natl Acad Sci U S A 91, no. 25 (December 6, 1994): 12008-12012. Link to Item
  - Perfect, JR, Toffaletti, DL, and Rude, TH. "The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid." Infect Immun 61, no. 10 (October 1993): 4446-4451. Link to Item
  - Toffaletti, DL, Rude, TH, Johnston, SA, Durack, DT, and Perfect, JR. "Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA." J Bacteriol 175, no. 5 (March 1993): 1405-1411. Link to Item
  - Lallinger, GJ, Reiner, SL, Cooke, DW, Toffaletti, DL, Perfect, JR, Granger, DL, and Durack, DT. "Efficacy of immune therapy in early experimental Naegleria fowleri meningitis." Infect Immun 55, no. 5 (May 1987): 1289-1293. Link to Item
  - Toffaletti, DL, Darrow, TL, and Scott, DW. "Augmentation of syngeneic tumor-specific immunity by semiallogeneic cell hybrids." J Immunol 130, no. 6 (June 1983): 2982-2986. Link to Item
  - DURACK, DT, and TOFFALETTI, DL. "A NEW METHOD FOR MEASUREMENT OF COMPLEMENT-MEDIATED SERUM BACTERICIDAL ACTIVITY." CLINICAL RESEARCH 30, no. 2 (1982): A518-A518. Link to Item
  - Toffaletti, D, Yoshida, T, and Cohen, S. "Interaction of macrophages and lymphocytes for lymphokine production and cellular proliferation." Cellular Immunology 56, no. 2 (1980): 487-501.
  - Toffaletti, DL, and Schwab, JH. "Modulation of lymphocyte functions by group A streptococcal membrane." Cell Immunol 42, no. 1 (January 1979): 3-17. Link to Item
  - TOFFALETTI, DL. "MACROPHAGE DEPENDENCE OF T-LYMPHOCYTE RESPONSES." FEDERATION PROCEEDINGS 37, no. 6 (1978): 1470-1470. Link to Item

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Education, Training, & Certifications

Duke Appointment History

Selected Grants

Selected Publications

Journal Articles