Viviana P. Ferreira, D.V.M., Ph.D.
Research Interests: The complement system uses a complex set of complement regulatory proteins that are either membrane-bound or in the fluid phase of plasma. Factor H is a soluble complement regulatory molecule with an essential role in the control of complement activation in plasma and on cell surfaces. Factor H polymorphisms and mutations have been linked to human diseases that often lead to severe complement-mediated tissue damage such as atypical hemolytic uremic syndrome, age-related macular degeneration, and membranoproliferative glomerulonephritis. We have shown that factor H is essential for the protection of cell surfaces using normal and paroxysmal nocturnal hemoglobinuric human red blood cells as models. My research on factor H focuses on understanding the molecular mechanisms of how factor H contributes to the protection of different cell surfaces from complement-mediated damage, and identifying how mutations in factor H affect its ability to protect cell surfaces. In addition, our research focuses on properdin, the only positive regulatory protein of the complement system. We and others have recently identified properdin as a pattern recognition molecule of the alternative pathway of complement and we are studying the molecular mechanisms involved in properdin-mediated complement regulation at the platelet/leukocyte interface. Altogether, this research will contribute to elucidating the role of complement regulatory proteins in the prevention or pathogenesis of inflammatory diseases (such as multiple cardiovascular diseases) where complement-mediated tissue damage is known to play important roles. This research has been made possible by support from the American Heart Association, the University of Toledo deArce-Koch Memorial Endowment Fund, and the National Institutes of Health.
Dr. Ferreira received her D.V.M. degree from The University of Chile. After research training at New York University under the direction of Dr. Elizabeth Nardin, Dr. Ferreira returned to Chile and obtained her Ph.D. in 2004 from the University of Chile, under the supervision of Dr. Arturo Ferreira (U. Chile) and Dr. Wilhelm Schwaeble (University of Leicester). She completed her postdoctoral training at the University of Texas in the laboratory of Dr. Michael Pangburn. Dr. Ferreira joined the Department of Medical Microbiology and Immunology in July, 2009.
Current Grant Support:
NHLBI/NIH R01 - Role of complement regulator properdin in the interaction between platelets and leukocytes; 06/01/14 -03/31/19
- 2012 UT Presidential Research Scholarship Award
- 2013 Dean’s Award for Teaching Excellence (Basic Sciences Junior Faculty)
- 2014 Dean’s Award for Research (New Investigator)
Research group (left to right): Adam Blatt (M.D./Ph.D. student); Sabina Pathan (2nd yr. medical school student); Heather Emch, Phys. Assist. (Research assistant); Viviana Ferreira, D.V.M., Ph.D.; Koustubh Kulkarni, M.S. (Research assistant).
Y.M. Ali, A. Hayat, B.M. Saeed, K.S. Haleem, S. Alshamrani, H.I. Kenawy, V.P. Ferreira, G. Saggu, A. Buchburger, P. Lachmann, R.B. Sim, D. Goundis, P.W. Andrew, N.J. Lynch, and W.J. Schwaeble. (2014). Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection. Proceedings of the National Academy of Sciences of the United States of America. 111(14):5301-5306.
M. Mulye, M. Bechill, W. Grose, V.P. Ferreira, E.R. Lafontaine, and R.M. Wooten. (2014). Delineating the importance of serum opsonins and the bacterial capsule in affecting the uptake and killing of Burkholderia pseudomallei by murine neutrophils and macrophages. PLoS Neglected Tropical Diseases. 8(8):e2988.
G. Mehta, V.P. Ferreira, C. Skerka, P.F. Zipfel, and N.K. Banda. (2014). New insights into disease-specific absence of complement factor H related protein C in mouse models of spontaneous autoimmune diseases. Molecular Immunology. 62(1):235-248.
G. Saggu, C. Cortes, H.N. Emch, G. Ramirez, R.G. Worth, and V.P. Ferreira*. (2013). Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O). *Corresponding author. Journal of Immunology. 190(12):6457-67. **Faculty of 1000 Medicine “Recommended” selection.
N.K. Banda, G. Mehta, V.P. Ferreira, C. Cortes, M. C. Pickering, M.K. Pangburn, W. P. Arend, and V.M. Holers. (2013). Essential role of surface-bound complement factor H in controlling immune complex-induced arthritis. Journal of Immunology. 190(7):3560-9.
B. Renner, J. Klawitter, R. Goldberg, J.W. McCullough, V.P. Ferreira, J.E. Cooper, U. Christians, and J.M. Thurman. (2013). Cyclosporine induces endothelial cells to release complement-activating microparticles. J Am Soc Nephrol. 24(11):1849-62.
C. Cortes, J.A. Ohtola, G. Saggu, V.P. Ferreira. (2013). Local release of properdin in the cellular microenvironment: role in pattern recognition and amplification of the alternative pathway of complement. *Corresponding author. Frontiers in Immunology (Molecular Innate Immunity Specialty Section). Volume 3 (article 412); doi: 10.3389/fimmu.2012.00412.
K. Takeda, J.M. Thurman, S. Tomlinson, M. Okamoto, Y. Shiraishi, V.P. Ferreira, C. Cortes, M.K. Pangburn, V.M. Holers, and E.W. Gelfand. (2012). The Critical Role of Complement Alternative Pathway Regulator Factor H in Allergen-Induced Airway Hyperresponsiveness and Inflammation. Journal of Immunology. 188(2):661-67.
B. Renner, V.P. Ferreira, C. Cortes, R. Goldberg, D. Ljubanovic, M.K. Pangburn, M.C. Pickering, S. Tomlinson, A. Holland-Neidermyer, D. Strassheim, V.M. Holers, and J.M. Thurman. (2011). Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury. Kidney International. 80(2):165-73.
C. Cortes, V.P. Ferreira, and M.K. Pangburn. (2011). Complement activation on chlamydia pneumoniae is accelerated by direct binding of native properdin to its surface. Infection and Immunity. 79(2):724-731.
G. Ramírez, C. Valck, V.P. Ferreira, N. López, and A. Ferreira. (2011). Extracellular Trypanosoma cruzi calreticulin in the host-parasite interplay. Trends in Parasitology. 27(3):115-22.
G. Ramírez, C. Valck, M.C. Molina, C.H. Ribeiro, N. López, G. Sanchez, V.P. Ferreira, R. Biletta, W. Schwaeble, and A. Ferreira. (2011). Trypanosoma cruzi calreticulin: A novel virulence factor that binds complement C1 on the parasite surface
and promotes infectivity. Immunobiology. 216(1-2):265-73.
V.P. Ferreira*, M.K. Pangburn, C. Cortés. (2010). Complement control protein factor H: the good, the bad, and the inadequate. *Corresponding author. Molecular Immunology. 47(13):2187-97.
S. Agarwal*, V.P. Ferreria*, C. Cortes, M.K. Pangburn, P.A. Rice, and S. Ram. (2010). An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitides. *Both authors contributed equally. J. Immunol. 185(1):507-516.
B. Renner, K. Coleman, R. Goldberg, C. Amura, A. Holland-Neidermyer, K. Pierce, H.N. Orth, H. Molina, V.P. Ferreira, C. Cortes, M.K. Pangburn, V.M. Holers, J.M. Thurman. (2010). The complement inhibitors Crry and factor H are critical for preventing autologous complement activation on renal tubular epithelial cells. Journal of Immunology. 185(5):3086-94.
B. Rohrer, Q. Long, B. Coughlin, B. Renner, Y. Huang, K. Kunchithapautham, V.P. Ferreira, M.K. Pangburn, G.S. Gilkeson, J.M. Thurman, S. Tomlinson, V.M. Holers. (2010). A targeted inhibitor of the complement alternative pathway reduces RPE injury and angiogenesis in models of age-related macular degeneration. Advances in Experimental Medicine and Biology. 703:137-49.
V.P. Ferreira*, C. Cortes, and M.K. Pangburn. (2010). Analysis of the complement functions of human properdin requires separation
of native polymeric forms from non-physiological aggregates. *Corresponding author.
C. Valck, G. Ramirez, N. Lopez, C.H. Ribeiro, I. Maldonado, G. Sanchez, V.P. Ferreira, W. Schwaeble, and A. Ferreira. (2010). Molecular mechanisms involved in the inactivation of the first component of human complement by Trypanosoma cruzi calreticulin Mol. Immunol. 47:1516-1521.
J.M. Thurman, B. Renner, K. Kunchithapautham, V.P. Ferreira, M.K. Pangburn, Z. Ablonczy, S. Tomlinson, V.M. Holers, and B. Rohrer. (2009) Oxidative Stress Renders Retinal Epithelial Cells Susceptible to Complement Mediated Injury. J. Biol. Chem. 284:16939-16947.
V.P. Ferreira, A. Herbert, C. Cortes, K.A. Mckee, B. Blaum, S.T. Esswein , D. Uhrin, P.N. Barlow, M.K. Pangburn, and D. Kavanagh. (2009) The binding of factor H to a complex of the physiological polyanions and C3b on the cell surface is impaired in atypical hemolytic uremic syndrome. J. Immunol. 182:7009-7018.
M.K. Pangburn, N. Rawal, C. Cortes, V.P. Ferreira, and M. Atkinson. (2009) Polyanion-induced self association of complement factor H: Possible mechanism of host protection from an innate immune system. J. Immunol. 182:1061-1068.
M.K. Pangburn, V.P. Ferreira*, and C. Cortes*. (2008) Discrimination between host and pathogens by the complement system. Vaccine. 26(Supplement 8):I15-21. *Both authors contributed equally.
H.G. Hocking, A.P. Herbert, D. Kavanagh, D.C. Soares, V.P. Ferreira, M.K. Pangburn, D. Uhrín, and P.N. Barlow. (2008) Structure of the N-terminal region of complement factor H and the conformational implications of disease-linked sequence variations. Journal of Biological Chemistry. 283:9475-9487.
V.P. Ferreira* and M.K. Pangburn. (2007) Factor H-mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. Blood. 110:2190-2192. *Corresponding author.
A.P. Herbert, J.A. Deakin, C.Q. Schmidt, B. Blaum, C. Egan, V.P. Ferreira, M.K. Pangburn, M. Lyon, D. Uhrín, and P.N. Barlow. (2007) Structure shows glycosaminoglycan- and protein-recognition site in factor H is perturbed by age-related macular degeneration-linked SNP. Journal of Biological Chemistry. 282:18960-18968.
V.P. Ferreira, A. Herbert, H. Hawkins, P. Barlow, and M.K. Pangburn. (2006) Critical role of the two C-terminal domains of factor H in regulating complement activation at cell surfaces. Journal of Immunology. 177:6308-6316.
L. Aguilar, G. Ramírez, C. Valck, M.C. Molina, A. Rojas, W. Schwaeble, V. Ferreira, and A. Ferreira. (2005) F(ab’)2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement. Biological Research. 38(2-3):187-195.
V. Ferreira, M.C. Molina, W. Schwaeble, D. Lemus, and A. Ferreira. (2005) Does Trypanosoma cruzi calreticulin modulate the complement system and angiogenesis? Trends in Parasitology. 21: 169-174.
M.C. Molina, V. Ferreira, C. Valck, G. Ramírez, L. Aguilar, A. Rojas, R. Billetta, D. Lemus, and A. Ferreira. (2005) An in vivo role for Trypanosoma cruzi calreticulin in antiangiogenesis. Molecular Biochemical Parasitology. 140:133-140.
V. Ferreira, C. Valck, G. Sanchez, A. Gingras, S. Tzima, M.C. Molina, W. Schwaeble and A. Ferreira. (2004) The classical activation pathway of the human complement system is specifically inhibited by calreticulin from Trypanosoma cruzi. Journal of Immunology. 172: 3042-3050.
V. Ferreira, M.C. Molina, C. Valck, A. Rojas, W. Schwaeble and A. Ferreira. (2004) Role of calreticulin from parasites in its interaction with vertebrate hosts. Molecular Immunology. 40: 1279-1291.
A. Aguirre, A. Escobar, V. Ferreira, M.C. Molina, A. Ferreira and J.C. Aguillón. (2003) An anti-human recombinant tumor necrosis factor alpha (TNF) monoclonal antibody recognizes an epitope in feline TNF. Vet. Res. 34:177-184.
J.C. Aguillón, A. Escobar, V. Ferreira, A. Aguirre, L. Ferreira, M.C. Molina and A. Ferreira. (2001) Daily production of human tumor necrosis factor in lipopolysaccharide (LPS)-stimulated ex vivo blood culture assays. European Cytokine Network. 12:105-110.
A. Moreno, R. Rodriguez, G. Oliveira, V. Ferreira, R. Nussenzweig, R. Moya-Castro, M. Calvo-Calle and E. Nardin. (1999) Pre-clinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice. Vaccine. 18: 89-99.
J.C. Aguillón, V. Ferreira, E. Núñez, L. Paredes, M.C Molina, A. Colombo, T. Hermosilla and A. Ferreira. (1996) Immunomodulation of LPS ability to induce local Shwartzman reaction. Scandinavian Journal of Immunology. 44: 551-555.
V. Ferreira and A. Ferreira. (2005) “Sistema del Complemento” (The Complement System). Book chapter in: Inmunología Básica y Clínica (Basic and Clinical Immunology). Mediterraneo Editorial. Pgs. 130-150.