Dena L. Toffaletti, PhD

Associate Professor in Medicine
Campus mail 337 Sands Bldg, Research Drive, Durham, NC 27710
Phone (919) 681-6276
Email address toffa001@mc.duke.edu

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

Education and Training

  • 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

Publications

Shaw, KJ, Schell, WA, Covel, J, Duboc, G, Giamberardino, C, Kapoor, M, Moloney, M, Soltow, QA, Tenor, JL, Toffaletti, DL, Trzoss, M, Webb, P, and Perfect, JR. "In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus." Antimicrobial Agents and Chemotherapy 62, no. 8 (August 2018).

PMID
29891599
Full Text

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).

PMID
28743811
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.

PMID
27212659
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.

PMID
24496797
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).

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." Eukaryotic Cell 12, no. 11 (November 2013): 1439-1450.

PMID
23975889
Full Text

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 Pathogens 9, no. 4 (January 2013): e1003247-null.

PMID
23592982
Full Text

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." The American Journal of Pathology 181, no. 4 (October 2012): 1356-1366.

PMID
22846723
Full Text

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-.

PMID
23028773
Full Text

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-.

PMID
22719877
Full Text

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