Scholars@Duke

• 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 - Chapel Hill 1977
• 

  Previous Appointments & Affiliations

  • Associate Professor in Medicine, Medicine, Infectious Diseases, Medicine 2010 - 2020
  • Assistant Professor in Medicine, Medicine, Infectious Diseases, Medicine 2006 - 2010
  • Assistant Research Professor in Medicine, Medicine, Infectious Diseases, Medicine 1994 - 2006
• Research
• 

  Selected Grants

  • Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS awarded by National Institutes of Health 2011 - 2023
  • AM-2-19 Efficacy Testing in a Mouse Model of Cryptococcosis awarded by Sfunga Therapeutics 2022
  • Pathobiology of C. neoformans in the Central Nervous System awarded by National Institutes of Health 2014 - 2020
  • 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
• 

  External Relationships

  • Becton, Dickinson and Company
  • Nova Biomedical
  • Werfen (formerly Instrumentation Laboratory)
• Publications & Artistic Works
• 

  Selected Publications

  • Academic Articles

    • Holcomb, Zachary E., Julie M. Steinbrink, Aimee K. Zaas, Marisol Betancourt, Jennifer L. Tenor, Dena L. Toffaletti, J Andrew Alspaugh, John R. Perfect, and Micah T. McClain. “Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.” J Fungi (Basel) 8, no. 5 (April 22, 2022). https://doi.org/10.3390/jof8050430.
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    • Wang, Yina, Maggie Wear, Gurkirat Kohli, Raghav Vij, Charles Giamberardino, Arpun Shah, Dena L. Toffaletti, et al. “Inositol Metabolism Regulates Capsule Structure and Virulence in the Human Pathogen Cryptococcus neoformans.” Mbio 12, no. 6 (December 21, 2021): e0279021. https://doi.org/10.1128/mBio.02790-21.
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    • Yu, Chen-Hsin, Poppy Sephton-Clark, Jennifer L. Tenor, Dena L. Toffaletti, Charles Giamberardino, Miriam Haverkamp, Christina A. Cuomo, and John R. Perfect. “Gene Expression of Diverse Cryptococcus Isolates during Infection of the Human Central Nervous System.” Mbio 12, no. 6 (December 21, 2021): e0231321. https://doi.org/10.1128/mBio.02313-21.
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    • Oliveira, Lana Sarita de Souza, Luciana Magalhães Pinto, Mariana Araújo Paulo de Medeiros, Dena L. Toffaletti, Jennifer L. Tenor, Tânia Fraga Barros, Rejane Pereira Neves, et al. “Comparison of Cryptococcus gattii/neoformans Species Complex to Related Genera (Papiliotrema and Naganishia) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility.” Front Cell Infect Microbiol 11 (2021): 642658. https://doi.org/10.3389/fcimb.2021.642658.
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    • Thanh, Lam Tuan, Dena L. Toffaletti, Jennifer L. Tenor, Charles Giamberardino, Gregory D. Sempowski, Yohannes Asfaw, Hai Trieu Phan, et al. “Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam.” Med Mycol 58, no. 8 (November 10, 2020): 1149–61. https://doi.org/10.1093/mmy/myaa013.
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    • Yu, Chen-Hsin, Yuan Chen, Christopher A. Desjardins, Jennifer L. Tenor, Dena L. Toffaletti, Charles Giamberardino, Anastasia Litvintseva, John R. Perfect, and Christina A. Cuomo. “Landscape of gene expression variation of natural isolates of Cryptococcus neoformans in response to biologically relevant stresses.” Microb Genom 6, no. 1 (January 2020). https://doi.org/10.1099/mgen.0.000319.
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    • So, Yee-Seul, Shinae Maeng, Dong-Hoon Yang, Hyelim Kim, Kyung-Tae Lee, Seong-Ryong Yu, Jennifer L. Tenor, et al. “Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans.” Msphere 4, no. 6 (November 20, 2019). https://doi.org/10.1128/mSphere.00785-19.
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    • Kovanda, Laura L., Charles Giamberardino, Laura McEntee, Dena L. Toffaletti, Kelly S. Franke, Andrew Bartuska, Gordon Smilnak, et al. “Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis.” Antimicrob Agents Chemother 63, no. 9 (September 2019). https://doi.org/10.1128/AAC.00546-19.
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    • Ponzio, Vinicius, Yuan Chen, Anderson Messias Rodrigues, Jennifer L. Tenor, Dena L. Toffaletti, José Osmar Medina-Pestana, Arnaldo Lopes Colombo, and John R. Perfect. “Genotypic diversity and clinical outcome of cryptococcosis in renal transplant recipients in Brazil.” Emerg Microbes Infect 8, no. 1 (2019): 119–29. https://doi.org/10.1080/22221751.2018.1562849.
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    • Shaw, Karen Joy, Wiley A. Schell, Jonathan Covel, Gisele Duboc, C. Giamberardino, Mili Kapoor, Molly Moloney, et al. “In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus.” Antimicrob Agents Chemother 62, no. 8 (August 2018). https://doi.org/10.1128/AAC.00523-18.
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    • Miao, Yi, Jennifer L. Tenor, Dena L. Toffaletti, Stacey A. Maskarinec, Jiuyu Liu, Richard E. Lee, John R. Perfect, and Richard G. Brennan. “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). https://doi.org/10.1128/mBio.00643-17.
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    • Homer, Christina M., Diana K. Summers, Alexi I. Goranov, Starlynn C. Clarke, Darin L. Wiesner, Jolene K. Diedrich, James J. Moresco, et al. “Intracellular Action of a Secreted Peptide Required for Fungal Virulence.” Cell Host Microbe 19, no. 6 (June 8, 2016): 849–64. https://doi.org/10.1016/j.chom.2016.05.001.
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    • Chen, Y., D. L. Toffaletti, J. L. Tenor, A. P. Litvintseva, C. Fang, T. G. Mitchell, T. R. McDonald, et al. “The Cryptococcus neoformans transcriptome at the site of human meningitis.” Mbio 5, no. 1 (February 4, 2014). https://doi.org/10.1128/mBio.01087-13.
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    • Chen, Yuan, Dena L. Toffaletti, Jennifer L. Tenor, Anastasia P. Litvintseva, Charles Fang, Thomas G. Mitchell, Tami R. McDonald, et al. “The Cryptococcus neoformans transcriptome at the site of human meningitis.” Mbio 5, no. 1 (February 4, 2014): e01087–e01013. https://doi.org/10.1128/mBio.01087-13.
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    • Frazzitta, Aubrey E., Haily Vora, Michael S. Price, Jennifer L. Tenor, Marisol Betancourt-Quiroz, Dena L. Toffaletti, Nan Cheng, and John R. Perfect. “Nitrogen source-dependent capsule induction in human-pathogenic cryptococcus species.” Eukaryot Cell 12, no. 11 (November 2013): 1439–50. https://doi.org/10.1128/EC.00169-13.
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    • Liu, Tong-Bao, Jong-Chul Kim, Yina Wang, Dena L. Toffaletti, Eliseo Eugenin, John R. Perfect, Kee Jun Kim, and Chaoyang Xue. “Brain inositol is a novel stimulator for promoting Cryptococcus penetration of the blood-brain barrier.” Plos Pathog 9, no. 4 (2013): e1003247. https://doi.org/10.1371/journal.ppat.1003247.
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    • He, Xiumiao, Daniel M. Lyons, Dena L. Toffaletti, Fuyuan Wang, Yafeng Qiu, Michael J. Davis, Daniel L. Meister, et al. “Virulence factors identified by Cryptococcus neoformans mutant screen differentially modulate lung immune responses and brain dissemination.” Am J Pathol 181, no. 4 (October 2012): 1356–66. https://doi.org/10.1016/j.ajpath.2012.06.012.
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    • Fang, Wei, Michael S. Price, Dena L. Toffaletti, Jennifer Tenor, Marisol Betancourt-Quiroz, Jennifer L. Price, Wei-hua Pan, Wan-qing Liao, and John R. Perfect. “Pleiotropic effects of deubiquitinating enzyme Ubp5 on growth and pathogenesis of Cryptococcus neoformans.” Plos One 7, no. 6 (2012): e38326. https://doi.org/10.1371/journal.pone.0038326.
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    • Tseng, Hsiang-Kuang, Chang-Pan Liu, Michael S. Price, Ambrose Y. Jong, Jui-Chih Chang, Dena L. Toffaletti, Marisol Betancourt-Quiroz, Aubrey E. Frazzitta, Wen-Long Cho, and John R. Perfect. “Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.” Plos One 7, no. 9 (2012): e45083. https://doi.org/10.1371/journal.pone.0045083.
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    • Price, M. S., M. Betancourt-Quiroz, J. L. Price, D. L. Toffaletti, H. Vora, G. Hu, J. W. Kronstad, and J. R. Perfect. “Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host.” Mbio 2, no. 3 (January 1, 2011). https://doi.org/10.1128/mBio.00103-11.
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    • Price, Michael S., Marisol Betancourt-Quiroz, Jennifer L. Price, Dena L. Toffaletti, Haily Vora, Guanggan Hu, James W. Kronstad, and John R. Perfect. “Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host.” Mbio 2, no. 3 (2011): e00103–11. https://doi.org/10.1128/mBio.00103-11.
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    • Lee, Anthony, Dena L. Toffaletti, Jennifer Tenor, Erik J. Soderblom, J Will Thompson, M Arthur Moseley, Michael Price, and John R. Perfect. “Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis.” Infect Immun 78, no. 10 (October 2010): 4213–25. https://doi.org/10.1128/IAI.00551-10.
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    • Ngamskulrungroj, Popchai, Uwe Himmelreich, Julia A. Breger, Christabel Wilson, Methee Chayakulkeeree, Mark B. Krockenberger, Richard Malik, et al. “The trehalose synthesis pathway is an integral part of the virulence composite for Cryptococcus gattii.” Infect Immun 77, no. 10 (October 2009): 4584–96. https://doi.org/10.1128/IAI.00565-09.
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    • Chayakulkeeree, Methee, Thomas H. Rude, Dena L. Toffaletti, and John R. Perfect. “Fatty acid synthesis is essential for survival of Cryptococcus neoformans and a potential fungicidal target.” Antimicrob Agents Chemother 51, no. 10 (October 2007): 3537–45. https://doi.org/10.1128/AAC.00442-07.
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    • Petzold, Elizabeth Wills, Uwe Himmelreich, Eleftherios Mylonakis, Thomas Rude, Dena Toffaletti, Gary M. Cox, Jackie L. Miller, and John R. Perfect. “Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans.” Infect Immun 74, no. 10 (October 2006): 5877–87. https://doi.org/10.1128/IAI.00624-06.
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    • Toffaletti, Dena L., Kirsten Nielsen, Fred Dietrich, Joseph Heitman, and John R. Perfect. “Cryptococcus neoformans mitochondrial genomes from serotype A and D strains do not influence virulence.” Curr Genet 46, no. 4 (October 2004): 193–204. https://doi.org/10.1007/s00294-004-0521-9.
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    • Miller, J. L., W. A. Schell, E. A. Wills, D. L. Toffaletti, M. Boyce, D. K. Benjamin, J. Bartroli, and J. R. Perfect. “In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans.” Antimicrob Agents Chemother 48, no. 2 (February 2004): 384–87. https://doi.org/10.1128/AAC.48.2.384-387.2004.
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    • Steen, B. R., S. Zuyderduyn, D. L. Toffaletti, M. Marra, S. J. M. Jones, J. R. Perfect, and J. Kronstad. “Cryptococcus neoformans gene expression during experimental cryptococcal meningitis.” Eukaryot Cell 2, no. 6 (December 2003): 1336–49. https://doi.org/10.1128/EC.2.6.1336-1349.2003.
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    • Luberto, Chiara, Beatriz Martinez-Mariño, Daniel Taraskiewicz, Benjamin Bolaños, Pasquale Chitano, Dena L. Toffaletti, Gary M. Cox, et al. “Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans.” J Clin Invest 112, no. 7 (October 2003): 1080–94. https://doi.org/10.1172/JCI18309.
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    • Nielsen, Kirsten, Gary M. Cox, Ping Wang, Dena L. Toffaletti, John R. Perfect, and Joseph Heitman. “Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.” Infect Immun 71, no. 9 (September 2003): 4831–41. https://doi.org/10.1128/IAI.71.9.4831-4841.2003.
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    • Toffaletti, Dena L., Maurizio Del Poeta, Thomas H. Rude, Fred Dietrich, and John R. Perfect. “Regulation of cytochrome c oxidase subunit 1 (COX1) expression in Cryptococcus neoformans by temperature and host environment.” Microbiology (Reading) 149, no. Pt 4 (April 2003): 1041–49. https://doi.org/10.1099/mic.0.26021-0.
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    • Rude, Thomas H., Dena L. Toffaletti, Gary M. Cox, and John R. Perfect. “Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans.” Infect Immun 70, no. 10 (October 2002): 5684–94. https://doi.org/10.1128/IAI.70.10.5684-5694.2002.
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    • Luberto, C., D. L. Toffaletti, E. A. Wills, S. C. Tucker, A. Casadevall, J. R. Perfect, Y. A. Hannun, and M. Del Poeta. “Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans.” Genes Dev 15, no. 2 (January 15, 2001): 201–12. https://doi.org/10.1101/gad.856001.
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    • Del Poeta, M., D. L. Toffaletti, T. H. Rude, C. C. Dykstra, J. Heitman, and J. R. Perfect. “Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target.” Genetics 152, no. 1 (May 1999): 167–78. https://doi.org/10.1093/genetics/152.1.167.
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    • Poeta, M. del, D. L. Toffaletti, T. H. Rude, S. D. Sparks, J. Heitman, and J. R. Perfect. “Cryptococcus neoformans differential gene expression detected in vitro and in vivo with green fluorescent protein.” Infect Immun 67, no. 4 (April 1999): 1812–20. https://doi.org/10.1128/IAI.67.4.1812-1820.1999.
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    • Thompson, J. R., C. M. Douglas, W. Li, C. K. Jue, B. Pramanik, X. Yuan, T. H. Rude, D. L. Toffaletti, J. R. Perfect, and M. Kurtz. “A glucan synthase FKS1 homolog in cryptococcus neoformans is single copy and encodes an essential function.” J Bacteriol 181, no. 2 (January 1999): 444–53. https://doi.org/10.1128/JB.181.2.444-453.1999.
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    • Firestine, S. M., S. Misialek, D. L. Toffaletti, T. J. Klem, J. R. Perfect, and V. J. Davisson. “Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis.” Arch Biochem Biophys 351, no. 1 (March 1, 1998): 123–34. https://doi.org/10.1006/abbi.1997.0512.
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    • Toffaletti, D. L., and J. R. Perfect. “Study of Cryptococcus neoformans actin gene regulation with a β-galactosidase-actin fusion.” Journal of Medical and Veterinary Mycology 35, no. 5 (November 24, 1997): 313–20.
    • Toffaletti, D. L., and J. R. Perfect. “Study of Cryptococcus neoformans actin gene regulation with a beta-galactosidase-actin fusion.” J Med Vet Mycol 35, no. 5 (September 1997): 313–20.
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    • Odom, A., S. Muir, E. Lim, D. L. Toffaletti, J. Perfect, and J. Heitman. “Calcineurin is required for virulence of Cryptococcus neoformans.” Embo J 16, no. 10 (May 15, 1997): 2576–89. https://doi.org/10.1093/emboj/16.10.2576.
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    • Cox, G. M., D. L. Toffaletti, and J. R. Perfect. “Dominant selection system for use in Cryptococcus neoformans.” J Med Vet Mycol 34, no. 6 (November 1996): 385–91.
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    • Cox, G. M., D. L. Toffaletti, and J. R. Perfect. “Dominant selection system for use in Cryptococcus neoformans.” Journal of Medical and Veterinary Mycology 34, no. 6 (January 1, 1996): 385–91. https://doi.org/10.1080/02681219680000691.
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    • Lodge, J. K., E. Jackson-Machelski, D. L. Toffaletti, J. R. Perfect, and J. I. Gordon. “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): 12008–12. https://doi.org/10.1073/pnas.91.25.12008.
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    • Perfect, J. R., D. L. Toffaletti, and T. H. Rude. “The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid.” Infect Immun 61, no. 10 (October 1993): 4446–51. https://doi.org/10.1128/iai.61.10.4446-4451.1993.
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    • Toffaletti, D. L., T. H. Rude, S. A. Johnston, D. T. Durack, and J. R. Perfect. “Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA.” J Bacteriol 175, no. 5 (March 1993): 1405–11. https://doi.org/10.1128/jb.175.5.1405-1411.1993.
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    • Lallinger, G. J., S. L. Reiner, D. W. Cooke, D. L. Toffaletti, J. R. Perfect, D. L. Granger, and D. T. Durack. “Efficacy of immune therapy in early experimental Naegleria fowleri meningitis.” Infect Immun 55, no. 5 (May 1987): 1289–93. https://doi.org/10.1128/iai.55.5.1289-1293.1987.
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    • Toffaletti, D. L., T. L. Darrow, and D. W. Scott. “Augmentation of syngeneic tumor-specific immunity by semiallogeneic cell hybrids.” J Immunol 130, no. 6 (June 1983): 2982–86.
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    • DURACK, D. T., and D. L. TOFFALETTI. “A NEW METHOD FOR MEASUREMENT OF COMPLEMENT-MEDIATED SERUM BACTERICIDAL ACTIVITY.” Clinical Research 30, no. 2 (January 1, 1982): A518–A518.
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    • Toffaletti, D., T. Yoshida, and S. Cohen. “Interaction of macrophages and lymphocytes for lymphokine production and cellular proliferation.” Cell Immunol 56, no. 2 (December 1980): 487–501. https://doi.org/10.1016/0008-8749(80)90123-9.
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    • Toffaletti, D. L., and J. H. Schwab. “Modulation of lymphocyte functions by group A streptococcal membrane.” Cell Immunol 42, no. 1 (January 1979): 3–17. https://doi.org/10.1016/0008-8749(79)90216-8.
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    • TOFFALETTI, D. L. “MACROPHAGE DEPENDENCE OF T-LYMPHOCYTE RESPONSES.” Federation Proceedings 37, no. 6 (January 1, 1978): 1470–1470.
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