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Carlos Subauste , MD

Professor
Medicine and Pathology
School of Medicine

Dr. Carlos Subauste undertook postdoctoral studies in Infectious Diseases and Immunology under Dr. Jack Remington at Stanford University. His area of research centered on host-pathogen interactions with an emphasis on the intracellular pathogen Toxoplasma gondii as a model organism. He joined the Departments of Medicine and Pathology at CWRU where he expanded his areas of research to cell signaling studies in inflammatory disorders.

For additional information about the Subauste Laboratory, please visit this website.

Research Information

Research Interests

The Subauste Lab conducts translational studies aimed at developing novel approaches to treat infections based on manipulation of host cell signaling (host-derived therapies) and developing new strategies to treat inflammatory/autoimmune disorders based on selective blockade of novel pro-inflammatory pathways. We pursue three areas of research:

Research Projects

  1. We study the molecular events by which intracellular pathogens manipulate host cell signaling to avoid lysosomal degradation. We focus on EGFR and Src signaling activated by T. gondii to block autophagy-mediated lysosomal degradation. These projects include in vitro cell signaling and imaging studies as well as in vivo studies using transgenic mice and animals treated with selective inhibitors.
  2. We examine the role of CD40 signaling as a regulator of key events in the development of diabetic retinopathy, the most common cause of visual loss in working age individuals. This work includes the use of transgenic mice with selective disruption of CD40-TRAF signaling that we developed in our laboratory and the use novel pharmacologic approaches to block this pathway for therapeutic purposes.
  3. Finally, we study CD40-TRAF signaling in mouse models of inflammatory bowel disease with the goal to develop and test small molecule inhibitors of CD40-driven inflammation.

Publications

See complete list of publications in the laboratory website:

  • Portillo JC, Yu JS, Vos S, Bapputty R, Lopez Corcino Y, Hubal A, Daw J, Arora S, Sun W, Lu ZR, Subauste CS. Disruption of retinal inflammation and the development of diabetic retinopathy in mice by a CD40-derived peptide or mutation of CD40 in Müller cells. Diabetologia. 2022 Dec;65(12):2157-2171. 
  • Yu JS, Daw J, Portillo JC, Subauste CS. CD40 Expressed in Endothelial Cells Promotes Upregulation of ICAM-1 But Not Pro-Inflammatory Cytokines, NOS2 and P2X7 in the Diabetic Retina. Invest Ophthalmol Vis Sci. 2021 Sep 2;62(12):22. 
  • Subauste CS. Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications. Front Cell Dev Biol. 2021 Jun 9;9:673813. 
  • Portillo JC, Yu JS, Hansen S, Kern TS, Subauste MC, Subauste CS. A cell-penetrating CD40-TRAF2,3 blocking peptide diminishes inflammation and neuronal loss after ischemia/reperfusion. FASEB J. 2021 Mar;35(3):e21412. 
  • Subauste CS. The CD40-ATP-P2X7 Receptor Pathway: Cell to Cell Cross-Talk to Promote Inflammation and Programmed Cell Death of Endothelial Cells. Front Immunol. 2019 Dec 17;10:2958. 
  • Lopez Corcino Y, Gonzalez Ferrer S, Mantilla LE, Trikeriotis S, Yu JS, Kim S, Hansen S, Portillo JC, Subauste CS. Toxoplasma gondii induces prolonged host epidermal growth factor receptor signalling to prevent parasite elimination by autophagy: Perspectives for in vivo control of the parasite. Cell Microbiol. 2019 Oct;21(10):e13084. 
  • Corcino YL, Portillo JC, Subauste CS. Epidermal growth factor receptor promotes cerebral and retinal invasion by Toxoplasma gondii. Sci Rep. 2019 Jan24;9(1):669. 
  • Portillo JC, Muniz-Feliciano L, Lopez Corcino Y, Lee SJ, Van Grol J, Parsons SJ, Schiemann WP, Subauste CS. Toxoplasma gondii induces FAK-Src-STAT3 signaling during infection of host cells that prevents parasite targeting by autophagy.PLoS Pathog. 2017 Oct 16;13(10):e1006671. 
  • Portillo JC, Lopez Corcino Y, Miao Y, Tang J, Sheibani N, Kern TS, Dubyak GR, Subauste CS. CD40 in Retinal Müller Cells Induces P2X7-Dependent Cytokine Expression in Macrophages/Microglia in Diabetic Mice and Development of Early Experimental Diabetic Retinopathy. Diabetes. 2017 Feb;66(2):483-493. 
  • Portillo JA, Greene JA, Okenka G, Miao Y, Sheibani N, Kern TS, Subauste CS. CD40 promotes the development of early diabetic retinopathy in mice. Diabetologia. 2014 Oct;57(10):2222-31. 
  • 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. PLoS Pathog. 2013;9(12):e1003809. 
  • 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. PLoS Pathog. 2013;9(8):e1003557. 
  • 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. J Clin Invest. 2006 Sep;116(9):2366-77.

Additional Information

For additional information about the Subauste Laboratory, please visit this website.