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Carlos Subauste, M.D.

Associate Professor of Medicine, Ophthalmology and Pathology,
 Case Western Reserve University

Division of Infectious Diseases & HIV Medicine

Email : carlos.subauste@case.edu
Office Phone : 2216.368.2785
Fax : 216.368.2034
Lab : BRB 448A
Lab Website: Subauste Lab
Appointments : 216.844.7890
Outpatient Clinic : Special Immunology Unit


  • M.D. : Universidad Peruana Cayetano Heredia, 1983
  • Residency : Internal Medicine, Southern Illinois University, 1984-1987
  • Chief Resident : Internal Medicine, Southern Illinois University, 1988
  • Fellowship, Infectious Diseases, Stanford University, 1988-1992

Research Interests

CD40 is a member of the TNF receptor superfamily that is expressed on a variety of hematopoietic and non-hematopoietic cells. CD40 is relevant to a broad array of diseases since CD40 is crucial for protection against many pathogens (Toxoplasma, Mycobacteria, Salmonella, Cryptosporydium, Cryptococcus, etc), and CD40 drives various diseases that have an inflammatory component (systemic lupus erythematosus and other autoimmune disorders, inflammatory bowel disease, graft rejection, microvascular complications of diabetes, atherosclerosis, ischemic tissue injury, etc).

Dr. Subauste's laboratory studies both aspects of CD40 biology.

1. His laboratory studies how CD40 confers protection against pathogens. The main focus is to determine how CD40 stimulates autophagy to kill T. gondii and the strategies used by the parasite to avoid autophagic killing. This is leading to testing novel therapeutic modalities against toxoplasmosis in mouse models of this disease.

2. Identification of novel strategies to block CD40-induced inflammation while attempting to preserve protection against pathogens. This work is being conducted in models of diabetes using transgenic mice made in the laboratory.

Selected References

    CD40 and Host Protection

  • Liu E, Van Grol J, Subauste CS. Atg5 but not Atg7 in dendritic cells enhances IL-2 and IFN-γ production by Toxoplasma gondii-reactive CD4(+) T cells.<http://www.ncbi.nlm.nih.gov/pubmed/25578385> Microbes Infect. 2015 Apr;17(4):275-84. doi: 10.1016/j.micinf.2014.12.008. Epub 2015 Jan 8. PubMed PMID: 25578385; PubMed Central PMCID: PMC4385469.
  • Muniz-Feliciano L, Van Grol J, Portillo JA, Liew L, Liu B, Carlin CR, Carruthers VB, Matthews S, Subauste CS. Toxoplasma gondii-induced activation of EGFR prevents autophagy protein-mediated killing of the parasite.<http://www.ncbi.nlm.nih.gov/pubmed/24367261> PLoS Pathog. 2013;9(12):e1003809. doi: 10.1371/journal.ppat.1003809. Epub 2013 Dec 19. PubMed PMID: 24367261; PubMed Central PMCID: PMC3868508.
  • Van Grol J, Muniz-Feliciano L, Portillo JA, Bonilha VL, Subauste CS. CD40 induces anti-Toxoplasma gondii activity in nonhematopoietic cells dependent on autophagy proteins.<http://www.ncbi.nlm.nih.gov/pubmed/23509150> Infect Immun. 2013 Jun;81(6):2002-11. doi: 10.1128/IAI.01145-12. Epub 2013 Mar 18. PubMed PMID: 23509150; PubMed Central PMCID: PMC3676008.
  • Ogolla PS, Portillo JA, White CL, Patel K, Lamb B, Sen GC, Subauste CS. The protein kinase double-stranded RNA-dependent (PKR) enhances protection against disease cause by a non-viral pathogen. <http://www.ncbi.nlm.nih.gov/pubmed/23990781> PLoS Pathog. 2013;9(8):e1003557. doi: 10.1371/journal.ppat.1003557. Epub 2013 Aug 22. PubMed PMID: 23990781; PubMed Central PMCID: PMC3749959.
  • Subauste CS, Ajzenberg D, Kijlstra A. Review of the series "Disease of the year 2011: toxoplasmosis" pathophysiology of toxoplasmosis.<http://www.ncbi.nlm.nih.gov/pubmed/21970661> Ocul Immunol Inflamm. 2011 Oct;19(5):297-306. doi: 10.3109/09273948.2010.605198. Review. PubMed PMID: 21970661.
  • Portillo JA, Okenka G, Reed E, Subauste A, Van Grol J, Gentil K, Komatsu M, Tanaka K, Landreth G, Levine B, Subauste CS. The CD40-autophagy pathway is needed for host protection despite IFN-γ-dependent immunity and CD40 induces autophagy via control of P21 levels.<http://www.ncbi.nlm.nih.gov/pubmed/21217818> PLoS One. 2010 Dec 31;5(12):e14472. doi: 10.1371/journal.pone.0014472. PubMed PMID: 21217818; PubMed Central PMCID: PMC3013095.
  • Van Grol J, Subauste C, Andrade RM, Fujinaga K, Nelson J, Subauste CS. HIV-1 inhibits autophagy in bystander macrophage/monocytic cells through Src-Akt and STAT3.<http://www.ncbi.nlm.nih.gov/pubmed/20661303> PLoS One. 2010 Jul 22;5(7):e11733. doi: 10.1371/journal.pone.0011733. PubMed PMID: 20661303; PubMed Central PMCID: PMC2908694.
  • Subauste CS. CD40 and the immune response to parasitic infections.<http://www.ncbi.nlm.nih.gov/pubmed/19616968> Semin Immunol. 2009 Oct;21(5):273-82. doi: 10.1016/j.smim.2009.06.003. Epub 2009 Jul 18. Review. PubMed PMID: 19616968; PubMed Central PMCID: PMC2758065.
  • Subauste CS. Autophagy in immunity against Toxoplasma gondii.<http://www.ncbi.nlm.nih.gov/pubmed/19802569> Curr Top Microbiol Immunol. 2009;335:251-65. doi: 10.1007/978-3-642-00302-8_12. Review. PubMed PMID: 19802569.
  • Subauste CS, Subauste A, Wessendarp M. Role of CD40-dependent down-regulation of CD154 in impaired induction of CD154 in CD4(+) T cells from HIV-1-infected patients.<http://www.ncbi.nlm.nih.gov/pubmed/17237414> J Immunol. 2007 Feb 1;178(3):1645-53. PubMed PMID: 17237414.
  • Subauste CS. Primary immunodeficiencies and susceptibility to parasitic infections.<http://www.ncbi.nlm.nih.gov/pubmed/17042928> Parasite Immunol. 2006 Nov;28(11):567-75. Review. PubMed PMID: 17042928.
  • Andrade RM, Wessendarp M, Gubbels MJ, Striepen B, Subauste CS. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes.<http://www.ncbi.nlm.nih.gov/pubmed/16955139> J Clin Invest. 2006 Sep;116(9):2366-77. PubMed PMID: 16955139; PubMed Central PMCID: PMC1555650.
  • Subauste CS, Wessendarp M. CD40 restrains in vivo growth of Toxoplasma gondii independently of gamma interferon.<http://www.ncbi.nlm.nih.gov/pubmed/16495528> Infect Immun. 2006 Mar;74(3):1573-9. PubMed PMID: 16495528; PubMed Central PMCID: PMC1418638.
  • Andrade RM, Wessendarp M, Portillo JA, Yang JQ, Gomez FJ, Durbin JE, Bishop GA, Subauste CS. TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha.<http://www.ncbi.nlm.nih.gov/pubmed/16237096> J Immunol. 2005 Nov 1;175(9):6014-21. PubMed PMID: 16237096.
  • CD40-Driven Inflammation

  • Portillo JA, Greene JA, Schwartz I, Subauste MC, Subauste CS. Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory responses in non-haematopoietic cells.<http://www.ncbi.nlm.nih.gov/pubmed/25051892> Immunology. 2015 Jan;144(1):21-33. doi: 10.1111/imm.12361. PubMed PMID: 25051892; PubMed Central PMCID: PMC4264907.
  • Portillo JA, Schwartz I, Zarini S, Bapputty R, Kern TS, Gubitosi-Klug RA, Murphy RC, Subauste MC, Subauste CS. Proinflammatory responses induced by CD40 in retinal endothelial and Müller cells are inhibited by blocking CD40-Traf2,3 or CD40-Traf6 signaling.<http://www.ncbi.nlm.nih.gov/pubmed/25477319> Invest Ophthalmol Vis Sci. 2014 Dec 4;55(12):8590-7. doi: 10.1167/iovs.14-15340. PubMed PMID: 25477319; PubMed Central PMCID: PMC4280881.
  • Portillo JA, Greene JA, Okenka G, Miao Y, Sheibani N, Kern TS, Subauste CS. CD40 promotes the development of early diabetic retinopathy in mice.<http://www.ncbi.nlm.nih.gov/pubmed/25015056> Diabetologia. 2014 Oct;57(10):2222-31. PubMed PMID: 25015056; PubMed Central PMCID: PMC4291184.
  • Portillo JA, Feliciano LM, Okenka G, Heinzel F, Subauste MC, Subauste CS. CD40 and tumour necrosis factor-α co-operate to up-regulate inducuble nitric oxide synthase expression in macrophages.<http://www.ncbi.nlm.nih.gov/pubmed/22044243> Immunology. 2012 Feb;135(2):140-50. doi: 10.1111/j.1365-2567.2011.03519.x. PubMed PMID: 22044243; PubMed Central PMCID: PMC3277716.
  • Portillo JA, Okenka G, Kern TS, Subauste CS. Identification of primary retinal cells and ex vivo detection of proinflammatory molecules using flow cytometry.<http://www.ncbi.nlm.nih.gov/pubmed/19626134> Mol Vis. 2009 Jul 17;15:1383-9. PubMed PMID: 19626134; PubMed Central PMCID: PMC2713733.
  • Portillo JA, Van Grol J, Zheng L, Okenka G, Gentil K, Garland A, Carlson EC, Kern TS, Subauste CS. CD40 mediates retinal inflammation and neurovascular degeneration.<http://www.ncbi.nlm.nih.gov/pubmed/19050292> J Immunol. 2008 Dec 15;181(12):8719-26. PubMed PMID: 19050292.