The main interest in our laboratory has been focused on the mechanisms of damage of some parasitic infections of public health problem in Mexico. The amebiasis is an infectious disease produced by the protozoan parasite Entamoeba histolytica. One of the interests has been the study of humoral and cellular immune responses (natural and specific immunities) and the cell changes produced during the host-parasite interaction in the intestine and the amebic liver abscess development. Using in vivo animal models of susceptibility and resistance to the disease, we are currently analyzing the role of several lectins and other molecules (cytokines, nitric oxide, oxidative stress, etc.) during the evolution of the lesions produced by E. histolytica. Moreover, our studies on the innate and specific immune responses have been related with the induction of protection against the infection.

Another important research line has been related with Free Living Amebas, especially Naegleria fowleri and Acanthamoeba spp. These amebas produce diverse types of human diseases, including the Primary Amebic Meningoencephalitis, Granulomatous Encephalitis and Amebic Keratitis (damage in the cornea). In our laboratory we have established in vivo animal models to determine the pathogenesis of the Amebic Keratitis and the Primary Amebic Meningoencephalitis. In these studies we are currently using different and new (molecular and cell biology, among others) methodologies that facilitate our understanding of the mechanisms of tissue invasion and damage. Our interest has been also focused on the role of the innate and specific responses that are involved in these infections.

In relation with chronic degenerative diseases, we are interested in the experimental liver cirrhosis and cancer liver. We are presently studying the role of inflammatory cells and reactive oxygen species (ROS) during the evolution of these important diseases. Using an experimental animal model (rat) we evaluate different anti-cirrhotic drugs that could be protect the liver as candidate for further treatment in humans

1. Shibayama, M., Navarro-García, F., López-Revilla, R., Martínez-Palomo, A. Tsutsumi, V. In vivo and in vitro intestinal amebiasis in Mongolian gerbils (Meriones unguiculatus). Parasitol Res. 1997; 83:170-176.


2. Shibayama, M., Campos-Rodríguez, R., Ramírez-Rosales, A., Flores-Romo, L., Espinosa-Castellano, M., Martínez-Palomo, A., Tsutsumi, V. Entamoeba histolytica: liver invasion and abscess production by intraperitoneal inoculation of trophozoites in hamsters, Mesocricetus auratus. Exp Parasitol. 1998; 88: 20-27.


3. Velázquez, C., Shibayama-Salas, M., Aguirre-García, J., Tsutsumi, V., Calderón, J. Role of neutrophils in innate resistance to Entamoeba histolytica liver infection in mice. Parasite Immunol. 1998; 20: 255-262.


4. Campos-Rodríguez, R, Jarillo-Luna, A., Ventura-Juárez, J., Shibayama, M., Serrano–Luna, J., Tsutsumi, V. Interaction of antibodies with Entamoeba histolytica trophozoites from experimental amebic liver abscess: An immunocytochemical study. Parasitol Res. 2000; 86: 603-607.


5. Pacheco-Yépez, J., Campos-Rodríguez, R., Shibayama, M., Ventura, J., Serrano-Luna, J., Tsutsumi, V. Entamoeba histolytica: production of nitric oxide and in situ activity of NADPH diaphorase in amebic liver abscess of hamster. Parasitol Res. 2001; 87: 49-56.


6. Muriel, P., Alba, N., Pérez-Álvarez, VM., Shibayama, M., Tsutsumi, V. Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride. Comp Biochem Phys C. 2001; 130:219-226.


7. Shibayama, M., Serrano-Luna, JJ., Rojas-Hernández, S., Campos-Rodríguez, R., Tsutsumi, V., Interaction of secretory immunoglobilin A antibodies with Naegleria fowleri trophozoites and collagen type I. Can J Microbiol. 2003; 49(3):164-170.


8. Muriel, P, Fernández-Martínez, E., Pérez-Álvarez, V., Lara-Ochoa, F., Ponce, S., García, J., Shibayama, M., Tsutsumi, V. Thalidomide ameliorates carbon tetrachloride induced cirrhosis in the rat. Eur J Gastroen Hepat. 2003; 15:1-7.


9. Falcón, V., Acosta-Rivero, N., Chinea, G., De la Rosa, MC., Menéndez, I., Dueñas-Carrera, S., Gra, B., Rodríguez, A., Tsutsumi, V., Shibayama, M., Luna-Muñoz, J., Miranda-Sánchez, MM., Morales, J., Kouri, J. Nuclear localization of nucleocapsid-like particles and HCV core protein in hepatocytes of a chronically HCV-infected patient. Biochem Bioph Res Com. 2003; 309:48-53.


10. Acosta-Rivero, N., Falcón, V., Álvarez, C., Musacchio, A., Chinea, G., De la Rosa, MC., Rodriguez, A., Dueñas-Carrera, S., Tsutsumi, V., Shibayama, M., Menéndez, I., Luna-Muñoz, J., Miranda-Sánchez, MM., Kouri, J., Morales-Grillo, J. Structured HCV nucleocapsids composed of P21 core protein assemble primary in the nucleus of Pichia pastoris yeast. Biochem Bioph Res Com. 2003; 309: 54-58.


11. Pacheco, J., Shibayama, M., Campos, R., Beck, DL., Houpt, E., Petri, WA., Tsutsumi, V. In vitro and in vivo interaction of Entamoeba histolytica Gal/GalNAc lectin with various target cells: An immunocytochemical analysis. Parasitol Int. 2004; 53(1): 35-47.


12. Ordaz-Pichardo, C., Shibayama, M., Villa-Treviño, S., Arriaga-Alba, M., Ángeles, E., De la Garza, M. Antiamoebic and Toxicity Studies of a Carbamic Acid Derivative and Its Therapeutic Effect in Hamster Model of Hepatic Amoebiasis. Antimicrob Agents Ch. 2005; 49 (3):1160-1168.


13. Falcón, V., Acosta-Rivero, N., Shibayama, M., Chinea, G., Gavilondo, JV., De la Rosa, MC., Menéndez, I., Gra, B., Dueñas-Carrera, S., Viña, A., García, W., González-Bravo, M., Luna-Muñoz, J., Miranda-Sánchez, M., Morales-Griollo, J., Kouri, J., Tsutsumi, V. HCV core protein localizes in the nuclei of nonparenchymal liver cells from chronically HCV-infected patients. Biochem Bioph Res Com. 2005; 329:1320-1328.


14. Falcón, V., Acosta-Rivero, N., Shibayama, M., Luna-Muñoz, J., Miranda-Sánchez, M., Gavilondo, JV., De la Rosa, MC., Menéndez, I., Gra, B., García, W., Dueñas-Carrera, S., Silva, J., Chinea, G., González-Bravo, M., Álvarez, F., Morales, J., Kouri, J., Tsutsumi, V. Detection of HCV Components and Pathological Reactions in Apoptotic Hepatocytes from Chronically HCV-infected Patients. Am J Inf Dis. 2005; 1 (1):12-24.


15. Falcón, V., Acosta-Rivero, N., Shibayama, M., Luna-Muñoz, J., Miranda-Sánchez, M., De la Rosa, MC., Menéndez, I., García, W., Gra, B., Dueñas-Carrera, S., Lopez, D., González-Bravo, M., Fernández-Ortega, C., Casillas, D., Morales, J., Kouri, J., Tsutsumi, V. Evidences of Apoptosis in Hepatitis C Virus-Infected Hepatocytes and Peripheral Blood Monocuclear Cells in the Absence of Liver Injury. Am J Inf Dis. 2005; 1 (1): 43-49.


16. Falcón, V., Acosta-Rivero, N., Shibayama, M., Luna-Muñoz, J., Miranda-Sánchez, M., De la Rosa, MC., Menéndez, I., Gra, Bienvenido., Dueñas-Carrera, S., García, W., Villar, E., Silva, J., López, D., González-Bravo, M., Fernández-Ortega, C., Casillas, D., Morales, J., Kouri, J., Tsutsumi, V. Evidences of hepatitis C virus replication in hepatocytes and peripheral blood mononuclear cells from patients negative for viral RNA in serum. Am J Inf Dis. 2005; 1 (1): 34-42.


17. Tsutsumi, V., Shibayama, M. Experimental Amebiasis: A Selected Review of Some In vivo Models. Arch Med Res. 2006; 37 (2):210-220.


18. Serrano-Luna, JJ., Cervantes-Sandoval, I., Calderón, J., Navarro-García, F., Tsutsumi, V., Shibayama, M. Protease activities of Acanthamoeba polyphaga and Acanthamoeba castellanii. Can J Microbiol. 2006; 52: 16-23.


19. Fernández-Martínez, E., Pérez-Alvarez, V., Tsutsumi, V., Shibayama, M., Muriel, P. Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. Exp Toxicol Pathol. 2006; 58: 49-58.


20. Reyes-Gordillo, K., Segovia, J., Shibayama, M., Vergara, P., Moreno, MG., Muriel, P. Curcumin protects against acute liver damage in the rat by inhibiting NF-kB, proinflammatory cytokines production and oxidative stress. Acta Bioch Bioph. 2007; 989-996. (derivado colaboración estudiante doctorado)


21. Shibayama, M., Dolabella, S., Silva, E., Tsutsumi, V. A Brazilian species of Entamoeba dispar (ADO) produces amoebic liver abscess in hamsters. Ann Hepatol. 2007; 6(2): Abril-Junio.117-118. (derivado colaboración Brasil, estancia doctorado)


22. Serrano-Luna, JJ., Cervantes-Sandoval, I., Tsutsumi, V., Shibayama, M. A Biochemical Comparison of Proteases from Pathogenic Naegleria fowleri and Non-pathogenic Naegleria gruberi. J Eukaryot Microbiol. 2007; 54(5): 411-417. (derivado tesista Licenciatura)


23. 23. Villalba, JD., Gómez, C., Medel, O., Sánchez, V., Carrero, JC., Shibayama, M., Pérez-Ishiwara, G. Programmed cell death in Entamoeba histolytica induced by the aminoglycoside G418. Microbiology. 2007; 153: 3852-3863. (derivado colaboración estudiante doctorado)


24. Cervantes-Sandoval, I., Serrano-Luna, JJ., Tapia-Malagón, J., Pacheco, J., Silva-Olivares, A., Galindo-Gomez, S., Tsutsumi, V., Shibayama, M. Characterization of Naegleria fowleri strains isolated from human cases of primary amoebic meningoencephalitis in Mexico. Rev Invest Clin. 2007; 59(5): 342-347. (derivado estudiante de maestría)


25. Villalba-Magdaleno, JD., Rojas, R., Gómez, C., Shibayama, M., Carrero, JC. Emetine produce Entamoeba histolytica death by inducing a programmed cell death. Am J Inf Dis. 2007; 3(2): 110-114. (derivado colaboración estudiante doctorado)


26. Chávez, E., Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Muriel, P. Resveratrol prevents fibrosis, NF-kB activation and TGF increases induced by chronic CCI4 treatment in rats. J Appl Toxicol. 2008; 28(1): 35-43. (derivado colaboración estudiante doctorado)


27. Rivera, H., Shibayama, M., Tsutsumi, V., Pérez-Alvarez, V., Muriel, P. Resveratrol and trimethylated resveratrol project from acute liver damage induced by CCl4 in the rat. J Appl Toxicol. 2008; 28(2): 147-155. (derivado colaboración estudiante doctorado)


28. Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Galicia-Moreno, G., Muriel, P. Curcumin prevents and reverses cirrhosis induced by bile duct obstruction or CCl4 in rats: role of TGF-? modulation and oxidative stress. Fund Clin Pharmacol. 2008; 22: 417-427. (derivado colaboración estudiante doctorado)


29. 2Galicia-Moreno, M., Rodríguez-Rivera, A., Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Moreno, M., Fernández-Martínez, E., Pérez-Álvarez, V., Muriel, P. Trolox down-regulates transforming growth factor-ß and prevents experimental cirrhosis. Basic Clin Pharmacol Toxicol. 2008; 103(5):476-481. (derivado colaboración doctorado)


30. Cervantes-Sandoval, I., Serrano-Luna, JJ., García-Latorre, E., Tsutsumi, V., Shibayama, M. Mucins in the host defense against Naegleria fowleri and mucinolytic activity as a possible means of evasión. Microbiology. 2008; 154(Pt12): 3895-3904. (derivado estudiante doctorado)


31. 3Cervantes-Sandoval, I., Serrano-Luna, JJ., García-Latorre, E., Tsutsumi, V., Shibayama, M. Characterization of Brain inflammation during primary amoebic meningoencephalitis. Parasitol Int. 2008; 57(3): 307-13. (derivado estudiante maestría)


32. Shibayama, M., Rivera-Aguilar, V., Barbosa-Cabrera, E., Rojas-Hernández, S., Jarillo-Luna, A., Tsutsumi, V., Pacheco-Yepez, J., Campos-Rodriguez, R. Innate immunity prevents tissue invasion by Entamoeba histolytica. Can J Microbiol. 2008; 54(12):1032-1042.


33. Pacheco-Yépez, J., Campos-Rodríguez, R., Rojas-Hernández, S., Serrano-Luna, JJ., Rivera-Aguilar, V., Villa-Treviño, S., Martínez-Palomo, A., Tsutsumi, V., Shibayama, M. Differential expression of surface glycoconjugates on Entamoeba histolytica and Entamoeba dispar. Parasitol Int. 2009; 58:171-177.


34. Cervantes-Sandoval, I., Serrano-Luna, JJ., Meza-Cervantes, P., Arroyo, R., Tsutsumi, V., Shibayama, M. Naegleria Fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation. Microbiology. 2009; 155: 3739-3747. (derivado estudiante doctorado)


35. Fernández-Martínez, E., Pérez-Hernández, N., Muriel, P., Pérez-Álvarez, V., Shibayama, M., Tsutsumi, V. The thalidomide analog 3-phtalmido-3-(3,4dimethoxiphenil)-propanoic acid improves the billiary cirrhosis in the rat. Exp Toxicol Pathol. 2009; 61(5): 471-479.

1. Cervantes-Sandoval, I., Serrano-Luna, JJ., Pacheco-Yépez, J., Silva-Olivares, A., Tsutsumi, V., Shibayama, M. Differences between Naegleria fowleri and Naegleria gruberi in expression of mannose and fucose glycoconjugates. Parasitol Res. 2010; 106(3): 695-701. (derivado estudiante doctorado)


2. Ximenéz, C., Cerrito, R., Rojas, L., Dolabella, S., Morán, P., Shibayama, M., González, E., Valadez, A., Hernández, E., Valenzuela, O., Limón, A., Partida, O., Silva, EF. Human Amebiasis: Breaking the paradigm?. Int J Environ Heal R. 2010; 7:1105-1120.


3. Chávez, E., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Castro-Sánchez, L., Pérez-Salazar, E., Moreno, MG., Muriel, P. Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat. Liver Int. 2010; 30(7): 969-978. (derivado colaboración estudiante doctorado)


4. Serrano-Luna, JJ., Gutiérrez-Meza, M., Mejía-Zepeda, R., Galindo-Gómez, S., Tsutsumi, V., Shibayama, M. Effect of phosphatidylcholine/cholesterol liposomes on Entamoeba histolytica virulence. Can J Microbiol. 2010; 56(12): 987-995. (derivado estudiante de Licenciatura/maestría)


5. González, E., García de León, MD., Meza, I., Ocadiz-Delgado, R., Gariglio, P., Silva-Olivares, A., Galindo-Gómez, S., Shibayama, M., Morán, P., Valadez, A., Limón, A., Rojas, L., Hernández, EG., Cerritos, R., Ximenez, C. Entamoeba histolytica calreticulin: an endoplasmic reticulum protein expressed by trophozoites into experimentally induced amoebic liver abscesses. Parasitol Res. 2011; 108: 439-449. (derivado colaboración estudiante doctorado


6. Sandoval-Bernal, G., Barbosa-Sabanero, G., Shibayama, M., Perez-Torres, A., Tsutsumi, V., Sabanero, M. Cell Wall Glycoproteins Participate in the Adhesion of Sporothrix schenckii to Ephithelial Cells. Mycopathologia. 2011; 171: 251-259. (derivado colaboración estudiante doctorado)


7. 42. Pacheco- Yépez, J., Galván-Moroyoqui, JM, Meza, I., Tsutsumi, V., Shibayama, M. Expression of cytokines and their regulation during amoebic liver abscess development. Parasite Immunol. 2011; 33(1): 56-64. (derivado colaboración estudiante doctorado)


8. Villalba-Magdaleno, JD., Pérez-Ishiwara, G., Serrano-Luna, J., Tsutsumi, V., Shibayama, M. In vivo programmed cell death of Entamoeba histolytica trophozoites in a hamster model of amoebic liver abscess. Microbiology. 2011; 157: 1489-1499. (Derivado estancia posdoctorado)


9. López, MF., Cano-Ramírez, C., Shibayama, M., Zuñiga, G. a-Pinene and Myrcene induce Ultrastructural Changes in the Midgut of Dendroctonus valens (Coleoptera: Curculionidae: Scolytinae). Ann Entomol Soc Am. 2011; 104(3): 553-561. (derivado estudiante licenciatura)


10. Moreno, MG., Chávez, E., Aldaba-Muruato, LR., Segovia, J., Vergara, P., Tsutsumi, V., Shibayama, M., Rivera-Espinoza, Y., Muriel, P. Coffee prevents CCI4-induced liver cirrhosis in the rat. Hepatol Int. 2011; 5: 857-863. (derivado colaboración estudiante doctorado)


11. Vivas-Mejía, PE., Rodríguez-Aguayo, C., Dong-Han, H., Sahahzad, M., Valiyeva, F., Shibayama, M., Chávez-Reyes, A., Sood, A., López-Berestein, G. Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer. Clin Cancer Res. 2011; 17(11): 3716-3726. (derivado estudiante doctorado)


12. Grajeda y Ortega, MA., Ortiz-Ordoñez, E., Favari, L., Shibayama, M., Silva-Olivares, A., López López, E. Biochemical and Mitochondrial Changes Induced by Cd, Fe and Zn in Limnodrillus hoffmeisteri. Int J Morphol. 2011; 29(2): 412-419.


13. Estrada-Figueroa, LA., Ramírez-Jímenez, Y., Osorio-Trujillo, C., Shibayama, M., Navarro-García, F., García-Tovar, C., Talámas-Rohana, P. Absence of CD38 Delays Arrival of Neutrophils to the Liver and Innate Immune Response Development During Hepatic Amoebiasis by Entamoeba Histolytica. Parasite Immunol. 2011; 33: 661-668. (derivado colaboración estudiante maestría)


14. Rivera, H., Morales-Ríos, MS., Bautista, W., Shibayama, M., Tsutsumi, V., Muriel, P., Pérez-Álvarez, V. A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage. Can J Physiol Pharmacol. 2011; 89: 759-766. (derivado colaboración estudiante doctorado)


15. Aldaba-Muruato, LR., Moreno, MG., Shibayama, M., Tsutsumi, V., Muriel, P. Protective effects of allopurinol againts acute liver damage and cirrhosis induced by carbon tetrachloride: Modulation of NF-KB, cytokine production and oxidative stress. Biochim Biophys Acta. 2012; 1820: 65-75. (derivado colaboración estudiante doctorado)


16. Santana-Dolabella, S., Serrano-Luna, J., Navarro-García, F., Cerritos, R., Ximénez, C., Galván-Moroyoqui, JM., Silva, EF., Tsutsumi, V., Shibayama, M. Amoebic liver abscess production by Entamoeba dispar. Ann Hepatol. 2012; 11(1): 107-117. (derivado colaboración Brasil, estudiante doctorado)


17. Chávez, E., Castro-Sánchez, L., Shibayama, M., Tsutsumi, V., Pérez-Salazar, E., Moreno, MG., Muriel, P. Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCI(4). J Appl Toxicol. 2012; 32(1): 51-59. (derivado colaboración estudiante doctorado)


18. Chávez, E., Castro-Sánchez, L., Shibayama, M., Tsutsumi, V., Moreno, MG., Muriel, P. Sulfasalazine prevents the increase in TGF-ß, COX-2, nuclear NFkB translocation and fibrosis in CCI4-induced liver cirrhosis in the rat. Hum Exp Toxicol. 2012; 31(9): 913-920. (Derivado colaboración estudiante doctorado)


19. Mejía García, A., Sánchez-Ocampo, EM., Galindo-Gómez, S., Shibayama, M., Reyes-Hernández, O., Guzmán-León, S., González, FJ., Elizondo, G. 2,3,7,8-Tetrachrlorodibenzo-p-dioxin enhances CCI4-induced hepatotoxicity in an aryl hydrocarbon receptor-dependent manner. Xenobiotica. 2012; Early Online: 1-8. (Derivado colaboración estudiante doctorado)


20. Debnath, A., Tunac, JB., Galido-Gómez, S., Silva-Olivares, A., Shibayama, M., McKerrow, JH. Corifungin: a new drug lead for Naegleria, identified from a high throughput screen. Antimicrob Agents Chemosther. 2012, 56(11): 5450-5457.


21. Guzmán-Medrano, R., Arreola-Rosales, RL., Shibayama, M., Silva-Olivares, DA., Bologna-Molina, R., Rodríguez, MA. Tumor associated macrophages and angiogenesis: a statistical correlation that could reflect a critical ralationship in ameloblastoma. Pathology-Research and Practice. 2012, 208: 672-676. (Derivado colaboración estudiante de doctorado)


22. Aldaba-Muruato, LR., Moreno, MG., Hernández-Mercado, E., Shibayama, M., Muriel, P. Secondary biliary cirrhosis in the rat is prevented by decreasing NF- ? B nuclear translocation and TGF- ß expression using allopurinol, an inhibitor of xanthine oxidase. Can J Physiol Pharmacol. 2012, 90(11): 1469-1478.


23. Shibayama, M., Martínez-Castillo, M., Silva-Olivares, A., Galindo-Gómez, S., Navarro-García, F., Escobar-Herrera, J., Sabanero, M., Tsutsumi, V., Serrano-Luna, J. Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri. Microbiology. 2012, 159(2): 205-419.