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Medical Microbiology and Immunology

Viviana P. Ferreira, D.V.M., Ph.D.

Viviana Ferreira

Associate Professor
Immunobiology of the Complement System听听

Office: HEB 235
Office telephone number: 419.383.6533
Fax number: 419.383.3002
Viviana.Ferreira@utoledo.edu

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Media Releases:




Research Interests and Biography:听

The complement system is an essential component of both the innate and adaptive immune system. It is comprised of about 50 proteins that function in a cascade-like activation process. The main outcomes of complement activation include pathogen clearance, inflammation, chemotaxis, and immune modulation, and others.听 Given the essential functions of complement, the system needs to be tightly regulated. Dr. Ferreira鈥檚 specialization in the complement system began during her Ph.D. training while working with calreticulin (TcCRT) from Trypanosoma cruzi, the causal agent of Chagas鈥� disease. TcCRT has the ability to bind to the initiating molecules of the classical and lectin pathways, inhibiting their activity as an immune-evasion strategy. Since 2004, her research has focused on human complement regulatory proteins of the alternative pathway of complement, Factor H and properdin, which play essential roles in various inherited and acquired diseases, including cardiovascular disease. In an effort to understand how complement regulatory protein Factor H recognizes and protects cell and tissue surfaces from complement-mediated attack, her research findings have unveiled novel molecular mechanisms involved in the pathogenesis of atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), and age-related macular degeneration. Recently, her laboratory has defined molecular mechanisms by which complement regulatory protein Factor H limits the formation of platelet/granulocyte aggregates (PGA) and how properdin promotes PGA formation.听 The laboratory has听also contributed to the understanding of how properdin may participate in听the pathogenesis听听of PNH and aHUS.听 Her main research focuses currently on understanding the molecular mechanisms involved in properdin structure/function in health and disease. Defining these mechanisms may identify new ways to treat and/or prevent inflammatory diseases.

Dr. Ferreira received a D.V.M. degree from The University of Chile School of Veterinary Medicine and, subsequently, a Ph.D. in Biomedical Sciences from The University of Chile School of Medicine.听 She completed her postdoctoral training at the University of Texas at Tyler and joined the Department of Medical Microbiology and Immunology in July 2009 as an Assistant Professor and was promoted to Associate Professor with tenure in 2015. Dr. Ferreira has completed a 4 year standing member term on the Innate Immunity and Inflammation NIH study section, a 3 year term on the American Association of Immunology Program Committee, and a 6 year term as a Councilor on the Board of the International Complement Society. She currently serves as the elected Treasurer/Officer on the Board of the International Complement Society, is Editor-in-Chief of the journal Immunobiology and is an Associate Editor for the Journal of Immunology.

Awards and Recognitions (selected):

Ferreira Lab 2017

Research group (left to right):听听 Jin Chen (Ph.D.; graduated 2019); Smrithi S.听Menon听(Ph.D.听candidate); Sara Moore (M.D./Ph.D.听candidate); Viviana Ferreira, D.V.M., Ph.D.

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听 (2023). A novel assay that characterizes properdin function shows neutrophil-derived properdin has a distinct oligomeric distribution.听 Front Immunol. 2023 Jan 12;13:918856. doi: 10.3389/fimmu.2022.918856.听

(2023). Complement: The Road Less Traveled. J Immunol. 2023 Jan 15;210(2):119-125. doi: 10.4049/jimmunol.2200540.

(2022). Factor H related proteins modulate complement activation on kidney cells. Kidney Int. 2022 Dec;102(6):1331-1344. doi: 10.1016/j.kint.2022.07.035. Epub 2022 Sep 3.PMID: 36063874.

(2022). Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation.Front Immunol.听2022;13:845953.听doi: 10.3389/fimmu.2022.845953.听eCollection 2022.听PubMed PMID: 35392081; PubMed Central PMCID: PMC8980529.听

(2022). The role of properdin and Factor H in disease.听Adv Immunol.听2022;153:1-90.听doi: 10.1016/bs.ai.2021.12.001.听Epub 2022 Feb 4.听Review.听PubMed PMID: 35469595.听

(2022). THE COMPLEMENT SYSTEM. Reference Module in Biomedical Sciences. Encyclopedia of Infection and Immunity. https://doi.org/10.1016/B978-0-12-818731-9.00056-2. Elsevier. 2022; 1:144-169.听

(2021). Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System? Front Immunol. 2021 Dec 16;12:789145. doi: 10.3389/fimmu.2021.789145.听*Corresponding author. 听

(2021). Hijacking Factor H for Complement Immune Evasion. Frontiers in Immunology. 12:602277. doi: 10.3389/fimmu.2021.602277. 2021. *Corresponding author.

 (2021). Mechanisms driving neutrophil-induced T-cell immunoparalysis in ovarian cancer. Cancer Immunol Res. doi: 10.1158/2326-6066.CIR-20-0922. 2021. **(2020).听Properdin is a key player in lysis of red blood cells and complement activation on endothelial cells in hemolytic anemias caused by complement dysregulation.听*Corresponding author. Frontiers in Immunology, 11:1460. doi: 10.3389/fimmu.2020.01460.

(2020). Characterization of binding properties of individual functional sites of human complement Factor H. *Corresponding author. Frontiers in Immunology. 11:1728. doi: 10.3389/fimmu.2020.01728.

. (2020). The interactions of parasite calreticulin with initial complement components: Consequences in immunity and virulence". *Corresponding author. Frontiers in Immunology. 11:1561. doi: 10.1016/j.pt.2020.01.007.

(2020). Increased alternative complement pathway function is associated with reduced mortality during critical illness. American Journal of Respiratory and Critical Care Medicine. 202(2):230-240. doi: 10.1164/rccm.201910-2083OC.

(2020). The role of properdin in killing of non-pathogenic Leptospira biflexa. Frontiers in Immunology. 11:572562. doi: 10.3389/fimmu.2020.572562. 2020.

(2020). Trypanosoma cruzi Calreticulin: Immune Evasion, Infectivity, and Tumorigenesis. Trends Parasitol.; 36(4):368-381. doi: 10.1016/j.pt.2020.01.007.

(2018) Properdin. Book chapter 27 in: The Complement Facts Book. 2nd edition. Editors: Scott Barnum and Theresa Schein. Elsevier Ltd. Paperback ISBN: 9780128104200.

(2018). Properdin: A multifaceted molecule involved in inflammation and diseases. *Corresponding Author. Mol Immunol. 102:58-72. doi: 10.1016/j.molimm.2018.05.018.

(2017). Factor H C-terminal domains are critical for regulation of platelent/granulocyte aggregate formation. *Corresponding Author. Frontiers in Immunology. 8:1586. doi: 10.3389/fimmu.2017.01586.

(2016). Rapamycin increases length and mechanosensory function of primary cilia in renal epithelial and vascular endothelial cells. International education and research journal. 2016; 2(12):91-97. NIHMSID: NIHMS838962.

. (2016). Properdin: a tightly regulated critical inflammatory modulator. *Corresponding author. Immunol Rev. 2016 Nov;274(1):172-190. doi: 10.1111/imr.12466.
.听Properdin-Mediated C5a Production Enhances Stable Binding of Platelets to Granulocytes in Human Whole Blood. *Corresponding author. Journal of Immunology.听196(11):4671-4680.听 doi: 10.4049/jimmunol.1600040.

听SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.听听Scientific Reports.听13;6:19300.听 doi: 10.1038/srep19300.

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.听 doi: 10.1073/pnas.1401011111.

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.听 doi: 10.1371/journal.pntd.0002988.

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.听 doi: 10.1016/j.molimm.2014.06.028.

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 鈥淩ecommended鈥� selection.听 doi: 10.4049/jimmunol.1300610.

. Essential role of surface-bound complement factor H in controlling immune complex-induced arthritis. Journal of Immunology. 190(7):3560-9.听 doi: 10.4049/jimmunol.1203271.

. Cyclosporine induces endothelial cells to release complement-activating microparticles. J Am Soc Nephrol. 24(11):1849-62.听 doi: 10.1681/ASN.2012111064.

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.

The Critical Role of Complement Alternative Pathway Regulator Factor H in Allergen-Induced Airway Hyperresponsiveness and Inflammation. Journal of Immunology. 188(2):661-67.听 doi: 10.4049/jimmunol.1101813.

Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury. Kidney International. 80(2):165-73.听 doi: 10.1038/ki.2011.115.

.听 (2011).听 Complement activation on chlamydia pneumoniae is accelerated by direct binding of native properdin to its surface.听 Infection and Immunity.听 79(2):724-731.听 doi: 10.1128/IAI.00980-10.

. (2011).听 Extracellular Trypanosoma cruzi calreticulin in the host-parasite interplay.听 Trends in Parasitology.听 27(3):115-22.听 doi: 10.1016/j.pt.2010.12.007.

. (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.听 doi: 10.1016/j.imbio.2010.04.001.

(2010). Complement control protein factor H: the good, the bad, and the inadequate. *Corresponding author. Molecular Immunology. 47(13):2187-97.听 doi: 10.1016/j.molimm.2010.05.007.

. (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.听听 doi: 10.4049/jimmunol.0903598.

. (2010).听 The complement inhibitors Crry and factor H are critical for preventing autologous complement activation on renal tubular epithelial cells.听Journal of Immunology.听 185(5):3086-94.听 doi: 10.4049/jimmunol.1000111.

(2010).听 A targeted inhibitor of the complement alternative pathway reduces RPE injury and angiogenesis in models of age-related macular degeneration.听 Advances in Experimental Medicine and Biology.听 703:137-49.听 doi: 10.1007/978-1-4419-5635-4_10.

. (2010). Analysis of the complement functions of human properdin requires separation of native polymeric forms from non-physiological aggregates. *Corresponding author. Immunobiology. 215(11):932-940. doi:10.1016/j.imbio.2010.02.002.

. (2010). Molecular mechanisms involved in the inactivation of the first component of human complement by Trypanosoma cruzi calreticulin听Mol. Immunol. 47:1516-1521.听 doi: 10.1016/j.molimm.2010.01.019.

. (2009) Oxidative Stress Renders Retinal Epithelial Cells Susceptible to Complement Mediated Injury. J. Biol. Chem. 284:16939-16947.听 doi: 10.1074/jbc.M808166200.

. (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.听182:7009-7018.听 doi: 10.4049/jimmunol.0804031.

. (2009) Polyanion-induced self association of complement factor H: Possible mechanism of host protection from an innate immune system. J. Immunol. 182:1061-1068.听
doi: 10.4049/jimmunol.182.2.1061.

(2008) Discrimination between host and pathogens by the complement system. *Both authors contributed equally. Vaccine. 26(Supplement 8):I15-21.听 doi: 10.1016/j.vaccine.2008.11.023.

. (2008)听 Structure of the N-terminal region of complement factor H and the conformational implications of disease-linked sequence variations. Journal of 听Biological Chemistry.听 283:9475-9487.听 doi: 10.1074/jbc.M709587200.

. (2007) Factor H-mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. *Corresponding author. Blood. 110:2190-2192.听 doi: 10.1182/blood-2007-04-083170.

. (2007) Structure shows glycosaminoglycan- and protein-recognition site in factor H is perturbed by age-related macular degeneration-linked SNP.听Journal of 听Biological Chemistry. 282:18960-18968.听 doi: 10.1074/jbc.M609636200.

. (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.听 doi: 10.4049/jimmunol.177.9.6308.

. (2005) F(ab鈥�)2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first听 component of human complement. Biological Research. 38(2-3):187-195.听 doi: 10.4067/s0716-97602005000200008.

. (2005) Does Trypanosoma cruzi calreticulin modulate the complement system and angiogenesis? Trends in Parasitology. 21: 169-174.听 doi: 10.1016/j.pt.2005.02.005.

. (2005) An in vivo role for Trypanosoma cruzi calreticulin in antiangiogenesis. Molecular Biochemical Parasitology. 140:133-140.听 doi: 10.1016/j.molbiopara.2004.12.014.

V. Ferreira and A. Ferreira. (2005) 鈥淪istema del Complemento鈥� (The Complement System). Book chapter in: Inmunolog铆a B谩sica y Cl铆nica (Basic and Clinical Immunology). Mediterraneo Editorial. Pgs. 130-150.

. (2004) The classical activation pathway of the human complement system is specifically inhibited by calreticulin from Trypanosoma cruzi.听 Journal of听Immunology. 172: 3042-3050.听 doi: 10.4049/jimmunol.172.5.3042

. (2004) Role of calreticulin from parasites in its interaction with vertebrate hosts. Molecular Immunology. 40: 1279-1291.听 doi: 10.1016/j.molimm.2003.11.018.

. (2003)听 An anti-human recombinant tumor necrosis factor alpha (TNF飩�) monoclonal antibody recognizes an epitope in feline TNF飩�.听 Vet. Res. 34:177-184.听 doi: 10.1051/vetres:2002064.

听 (2001)听Daily production of human tumor necrosis factor in lipopolysaccharide (LPS)-stimulated ex vivo blood culture assays.听European Cytokine Network.听 12:105-110.听 PMID: 11282553.

. (1999) Pre-clinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice. Vaccine. 18: 89-99.听 doi: 10.1016/s0264-410x(99)00184-x.

.听 (1996)听 Immunomodulation of LPS ability to induce local Shwartzman reaction. Scandinavian Journal of Immunology. 44: 551-555.听 doi: 10.1046/j.1365-3083.1996.d01-345.x.

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