Dr Fernando Fonseca Guimaraes

Senior Research Fellow

The University of Queensland Diamantina Institute
Faculty of Medicine

Overview

I completed my doctoral degree as part of the International PhD Program at Institute Pasteur (Paris, France) in 2012. During my PhD, I laid strong foundations for my academic career and became a key researcher in the field of NK cell response to systemic inflammatory response syndrome and sepsis in animal models and intensive care unit (ICU) patients. In 2013, I joined QIMR as a postdoctoral fellow, and in 2016 I moved to the Immunotherapy Laboratory at WEHI to extend my knowledge in the areas of cancer immunoediting and immunotherapy under Prof. Nick Huntington mentorship. I started to gain independence by attracting peer-reviewed funding: an NHMRC ECF Peter Doherty Fellowship, an NHMRC New Investigator Project Grant, a National Breast Cancer Foundation Fellowship, three Cure Cancer Australia (CCA) PdCCRS Project Grants, and a Weekend to End Women's Cancer Grant as sole chief investigator. From my postdoctoral training, I have an extensive track record of publications in top tier journals including Blood, Cell Death Dis, JEM, PNAS, Nat Comms and Nat Immunol (total 58 papers since 2009 including 19 as first author, 8 as corresponding author, 8 invited reviews), and was awarded the 2019 Researcher of the Year by CCA. My work in the identification of new regulators of optimal in vivo NK cell function has earned me peer recognition as an emerging leader in this field. My current projects at the University of Queensland Diamantina Institute aim to identify and translate the role of NK cells and develop novel immunotherapy approaches for different diseases.

Research Interests

  • Natural Killer (NK) cell biology
    Study of innate NK cell lymphocytes from cellular development to function
  • Experimental and translational immunology
    Development of novel immunotherapeutic approaches to treat diseases

Qualifications

  • Doctor of Philosophy, Institute Pasteur & University Paris

Publications

  • Best, Sarah A., Hess, Jonas B., Souza-Fonseca-Guimaraes, Fernando, Cursons, Joseph, Kersbergen, Ariena, Dong, Xueyi, Rautela, Jai, Hyslop, Stephanie R., Ritchie, Matthew E., Davis, Melissa J., Leong, Tracy L., Irving, Louis, Steinfort, Daniel, Huntington, Nicholas D. and Sutherland, Kate D. (2020). Harnessing natural killer immunity in metastatic SCLC. Journal of Thoracic Oncology doi: 10.1016/j.jtho.2020.05.008

  • Louis, Cynthia, Souza-Fonseca-Guimaraes, Fernando, Yang, Yuyan, D'Silva, Damian, Kratina, Tobias, Dagley, Laura, Hediyeh-Zadeh, Soroor, Rautela, Jai, Masters, Seth Lucian, Davis, Melissa J., Babon, Jeffrey J., Ciric, Bogoljub, Vivier, Eric, Alexander, Warren S., Huntington, Nicholas D. and Wicks, Ian P. (2020). Erratum: Erutam: NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS (Journal of Experimental Medicine (2020) 217:5 DOI: 10.1084/jem.20191421). Journal of Experimental Medicine, 217 (5) e2019142103192020c doi: 10.1084/jem.2019142103192020c

  • Chew, Hui Yi, De Lima, Priscila O., Gonzalez Cruz, Jazmina L., Banushi, Blerida, Echejoh, Godwins, Hu, Lingbo, Joseph, Shannon R., Lum, Benedict, Rae, James, O'Donnell, Jake S., Merida de Long, Lilia, Okano, Satomi, King, Brigid, Barry, Rachael, Moi, Davide, Mazzieri, Roberta, Thomas, Ranjeny, Souza-Fonseca-Guimaraes, Fernando, Foote, Matthew, McCluskey, Adam, Robinson, Phillip J., Frazer, Ian H., Saunders, Nicholas A., Parton, Robert G., Dolcetti, Riccardo, Cuff, Katharine, Martin, Jennifer H., Panizza, Benedict, Walpole, Euan ... Simpson, Fiona (2020). Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies. Cell, 180 (5), 895-914.e27. doi: 10.1016/j.cell.2020.02.019

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Supervision

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Available Projects

  • Background: Despite advances in treatment and earlier detection, cancer is still a main cause of cancer death worldwide. Natural killer (NK) cells are circulating innate lymphocytes that naturally protect against tumor spread (metastasis), and recently showed by our group as dysfunctional in the tumour microenvironment (TME) established by cancers at distant organs for future metastatic spread. Yet, despite knowing that NK cells do control cancer metastasis, our knowledge of how cancer cells evade NK cell control is still very poor. This project aims to examine several immune suppressive pathways that cancers likely manipulate to avoid NK cells and spread. These include factors the transforming growth factor (TGF)-β superfamily that are elevated in the tumor environment. These molecules have great potential to suppress the normally high killing and anti-metastatic activity mediated by NK cells, but to date we still need to elucidate how relatively important each pathway might be.

    Proposed research program: The intrinsic NK cell function under suppressive factors stimulation will be assessed with NK cells purified from mouse spleen (wild type) by cell sorter, and in vitro challenge with activating cytokines and suppressive factors. Aim-1: Which suppressive factor is a major inhibitor of NK cell killing activity? This aim will be screened by killing activity of NK cells versus target tumour cells in co-culture systems. Aim-2: Which suppressive factor is a major inhibitor of NK cell cytokine secretion? This aim will assess NK cell cytokine production by intracellular cytokine (e.g. IFN-gamma) staining (flow cytometry) and secreted IFN-gamma, among others, from culture supernatants (ELISA); Aim-3: What is the cellular signalling status under suppressive conditions? The identification of altered cellular signalling will be screened by intracellular staining of phosphorylated signalling molecules (phosphor(p)-AKT, p-ERK1/2, p-p38, p-phospholipase C-gamma2, p-phosphotyrosine, p-SMAD2,3, p-STAT4, p-STAT5 and p-ZAP70 (PhosphoFlow).

    These experimental tools will determine which is the most important suppressive pathway in inhibiting NK cell functions. Information we obtain from this work will allow us to design rationale approaches to increase NK cell function in personalised immunotherapy approaches.

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Publications

Journal Article

  • Best, Sarah A., Hess, Jonas B., Souza-Fonseca-Guimaraes, Fernando, Cursons, Joseph, Kersbergen, Ariena, Dong, Xueyi, Rautela, Jai, Hyslop, Stephanie R., Ritchie, Matthew E., Davis, Melissa J., Leong, Tracy L., Irving, Louis, Steinfort, Daniel, Huntington, Nicholas D. and Sutherland, Kate D. (2020). Harnessing natural killer immunity in metastatic SCLC. Journal of Thoracic Oncology doi: 10.1016/j.jtho.2020.05.008

  • Louis, Cynthia, Souza-Fonseca-Guimaraes, Fernando, Yang, Yuyan, D'Silva, Damian, Kratina, Tobias, Dagley, Laura, Hediyeh-Zadeh, Soroor, Rautela, Jai, Masters, Seth Lucian, Davis, Melissa J., Babon, Jeffrey J., Ciric, Bogoljub, Vivier, Eric, Alexander, Warren S., Huntington, Nicholas D. and Wicks, Ian P. (2020). Erratum: Erutam: NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS (Journal of Experimental Medicine (2020) 217:5 DOI: 10.1084/jem.20191421). Journal of Experimental Medicine, 217 (5) e2019142103192020c doi: 10.1084/jem.2019142103192020c

  • Chew, Hui Yi, De Lima, Priscila O., Gonzalez Cruz, Jazmina L., Banushi, Blerida, Echejoh, Godwins, Hu, Lingbo, Joseph, Shannon R., Lum, Benedict, Rae, James, O'Donnell, Jake S., Merida de Long, Lilia, Okano, Satomi, King, Brigid, Barry, Rachael, Moi, Davide, Mazzieri, Roberta, Thomas, Ranjeny, Souza-Fonseca-Guimaraes, Fernando, Foote, Matthew, McCluskey, Adam, Robinson, Phillip J., Frazer, Ian H., Saunders, Nicholas A., Parton, Robert G., Dolcetti, Riccardo, Cuff, Katharine, Martin, Jennifer H., Panizza, Benedict, Walpole, Euan ... Simpson, Fiona (2020). Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies. Cell, 180 (5), 895-914.e27. doi: 10.1016/j.cell.2020.02.019

  • Louis, Cynthia, Souza-Fonseca-Guimaraes, Fernando, Yang, Yuyan, D’Silva, Damian, Kratina, Tobias, Dagley, Laura, Hediyeh-Zadeh, Soroor, Rautela, Jai, Masters, Seth Lucian, Davis, Melissa J., Babon, Jeffrey J., Ciric, Bogoljub, Vivier, Eric, Alexander, Warren S., Huntington, Nicholas D. and Wicks, Ian P. (2020). NK cell–derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS. Journal of Experimental Medicine, 217 (5) e20191421 doi: 10.1084/jem.20191421

  • Delconte, Rebecca B., Guittard, Geoffrey, Goh, Wilford, Hediyeh-Zadeh, Soroor, Hennessy, Robert J., Rautela, Jai, Davis, Melissa J., Souza-Fonseca-Guimaraes, Fernando, Nunes, Jacques A. and Huntington, Nicholas D. (2020). NK cell priming from endogenous homeostatic signals is modulated by CIS. Frontiers in Immunology, 11 75, 75. doi: 10.3389/fimmu.2020.00075

  • Rossi, Gustavo Rodrigues, Trindade, Edvaldo S. and Souza-Fonseca-Guimaraes, Fernando (2020). Tumor microenvironment-associated extracellular matrix components regulate NK cell function. Frontiers in Immunology, 11 73, 73. doi: 10.3389/fimmu.2020.00073

  • Rautela, Jai, Dagley, Laura F., Kratina, Tobias, Anthony, Angaleena, Goh, Wilford, Surgenor, Elliot, Delconte, Rebecca B., Webb, Andrew I., Elwood, Ngaire, Groom, Joanna R., Souza-Fonseca-Guimaraes, Fernando, Corcoran, Lynn and Huntington, Nicholas D. (2019). Generation of novel Id2 and E2-2, E2A and HEB antibodies reveals novel Id2 binding partners and species-specific expression of E-proteins in NK cells. Molecular Immunology, 115, 56-63. doi: 10.1016/j.molimm.2018.08.017

  • Rautela, Jai, Dagley, Laura F., de Oliveira, Carolina C., Schuster, Iona S., Hediyeh-Zadeh, Soroor, Delconte, Rebecca B., Cursons, Joseph, Hennessy, Robert, Hutchinson, Dana S., Harrison, Craig, Kita, Badia, Vivier, Eric, Webb, Andrew I., Degli-Esposti, Mariapia A., Davis, Melissa J., Huntington, Nicholas D. and Souza-Fonseca-Guimaraes, Fernando (2019). Therapeutic blockade of activin-A improves NK cell function and antitumor immunity. Science Signaling, 12 (596) aat7527, eaat7527. doi: 10.1126/scisignal.aat7527

  • Cursons, Joseph, Souza-Fonseca-Guimaraes, Fernando, Foroutan, Momeneh, Anderson, Ashley, Hollande, Frédéric, Hediyeh-Zadeh, Soroor, Behren, Andreas, Huntington, Nicholas D. and Davis, Melissa J. (2019). A gene signature predicting natural killer cell infiltration and improved survival in melanoma patients. Cancer Immunology Research, 7 (7), 1162-1174. doi: 10.1158/2326-6066.cir-18-0500

  • Healy, Lachlan P., Rossi, Gustavo R., Rautela, Jai, Slade, Charlotte A., Huntington, Nicholas D., Winship, Ingrid M. and Souza-Fonseca-Guimaraes, Fernando (2019). Loss-of-Function in SMAD4 Might Not Be Critical for Human Natural Killer Cell Responsiveness to TGF-β. Frontiers in Immunology, 10 (MAY) 904 doi: 10.3389/fimmu.2019.00904

  • Lelliott, Emily J., Cullinane, Carleen, Martin, Claire A., Walker, Rachael, Ramsbottom, Kelly M., Souza-Fonseca-Guimaraes, Fernando, Abuhammad, Shatha, Michie, Jessica, Kirby, Laura, Young, Richard J., Slater, Alison, Lau, Peter, Meeth, Katrina, Oliaro, Jane, Haynes, Nicole, McArthur, Grant A. and Sheppard, Karen E. (2019). A novel immunogenic mouse model of melanoma for the preclinical assessment of combination targeted and immune-based therapy. Scientific Reports, 9 (1) 1225 doi: 10.1038/s41598-018-37883-y

  • Souza-Fonseca-Guimaraes, Fernando, Cursons, Joseph and Huntington, Nicholas D. (2019). The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy. Trends in Immunology, 40 (2), 142-158. doi: 10.1016/j.it.2018.12.003

  • Briassoulis, George, Briassoulis, Panagiotis, Miliaraki, Marianna, Ilia, Stavroula, Parlato, Marianna, Philippart, François, Rouquette, Alexandra, Moucadel, Virginie, Cavaillon, Jean-Marc, Misset, Benoît, Combined Approach for The eArly diagnosis of INfection in sepsis (CAPTAIN) study group and Guimaraes, Fernando (2019). Biomarker cruises in sepsis: who is the CAPTAIN? Discussion on “Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study”. Intensive Care Medicine, 45 (1), 132-133. doi: 10.1007/s00134-018-5451-y

  • Sheikh, Amania A., Cooper, Lucy, Feng, Meiqi, Souza-Fonseca-Guimaraes, Fernando, Lafouresse, Fanny, Duckworth, Brigette C., Huntington, Nicholas D., Moon, James J., Pellegrini, Marc, Nutt, Stephen L., Belz, Gabrielle T., Good-Jacobson, Kim L. and Groom, Joanna R. (2019). Context-dependent role for T-bet in T follicular helper differentiation and germinal center function following viral infection. Cell Reports, 28 (7), 1758-1772.e4. doi: 10.1016/j.celrep.2019.07.034

  • Tye, Hazel, Yu, Chien-Hsiung, Simms, Lisa A., de Zoete, Marcel R., Kim, Man Lyang, Zakrzewski, Martha, Penington, Jocelyn S., Harapas, Cassandra R., Souza-Fonseca-Guimaraes, Fernando, Wockner, Leesa F., Preaudet, Adele, Mielke, Lisa A., Wilcox, Stephen A., Ogura, Yasunori, Corr, Sinead C., Kanojia, Komal, Kouremenos, Konstantinos A., De Souza, David P., McConville, Malcolm J., Flavell, Richard A., Gerlic, Motti, Kile, Benjamin T., Papenfuss, Anthony T., Putoczki, Tracy L., Radford-Smith, Graham L. and Masters, Seth L. (2018). NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease. Nature Communications, 9 (1) 3728, 3728. doi: 10.1038/s41467-018-06125-0

  • Jiao, Yuhao, Davis, Joanne E., Rautela, Jai, Carrington, Emma M., Ludford-Menting, Mandy J., Goh, Wilford, Delconte, Rebecca B., Souza-Fonseca-Guimaraes, Fernando, Koldej, Rachel, Gray, Daniel, Huang, David, Kile, Ben T., Lew, Andrew M., Ritchie, David S. and Huntington, Nicholas D. (2018). Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes. Cell Death & Differentiation, 26 (8), 1516-1530. doi: 10.1038/s41418-018-0228-y

  • Sun, Li, Rautela, Jai, Delconte, Rebecca B., Souza-Fonseca-Guimaraes, Fernando, Carrington, Emma M., Schenk, Robyn L., Herold, Marco J., Huntington, Nicholas D., Lew, Andrew M., Xu, Yuekang and Zhan, Yifan (2018). GM-CSF quantity has a selective effect on granulocytic vs. monocytic myeloid development and function. Frontiers in Immunology, 9 doi: 10.3389/fimmu.2018.01922

  • Parlato, Marianna, Philippart, François, Rouquette, Alexandra, Moucadel, Virginie, Puchois, Virginie, Blein, Sophie, Bedos, Jean-Pierre, Diehl, Jean-Luc, Hamzaoui, Olfa, Annane, Djillali, Journois, Didier, Ben Boutieb, Myriam, Estève, Laurent, Fitting, Catherine, Treluyer, Jean-Marc, Pachot, Alexandre, Adib-Conquy, Minou, Cavaillon, Jean-Marc, Misset, Benoît, Jacqmin, Sébastien, Lagrange, Alix, de Pinot de Villechenon, Gabrielle, Aissaoui, Nadia, Guerot, Emmanuel, Venot, Marion, Prat, Dominique, Sztrymf, Benjamin, Maxime, Virginie, Polito, Andrea ... Souza-Fonseca-Guimaraes, Fernando (2018). Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study. Intensive Care Medicine, 44 (7), 1061-1070. doi: 10.1007/s00134-018-5228-3

  • Rautela, Jai, Souza-Fonseca-Guimaraes, Fernando, Hediyeh-Zadeh, Soroor, Delconte, Rebecca B., Davis, Melissa J. and Huntington, Nicholas D. (2018). Molecular insight into targeting the NK cell immune response to cancer. Immunology and Cell Biology, 96 (5), 477-484. doi: 10.1111/imcb.12045

  • Young, Arabella, Ngiow, Shin Foong, Gao, Yulong, Patch, Ann-Marie, Barkauskas, Deborah S., Messaoudene, Meriem, Lin, Gene, Coudert, Jerome D., Stannard, Kimberley A., Zitvogel, Laurence, Degli-Esposti, Mariapia A., Vivier, Eric, Waddell, Nicola, Linden, Joel, Huntington, Nicholas D., Souza-Fonseca-Guimaraes, Fernando and Smyth, Mark J. (2018). A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Cancer Research, 78 (4), 1003-1016. doi: 10.1158/0008-5472.CAN-17-2826

  • Ng, Susanna S., Souza-Fonseca-Guimaraes, Fernando, Rivera, Fabian de Labastida, Amante, Fiona H., Kumar, Rajiv, Gao, Yulong, Sheel, Meru, Beattie, Lynette, de Oca, Marcela Montes, Guillerey, Camille, Edwards, Chelsea L., Faleiro, Rebecca J., Frame, Teija, Bunn, Patrick T., Vivier, Eric, Godfrey, Dale I., Pellicci, Daniel G., Lopez, J. Alejandro, Andrews, Katherine T., Huntington, Nicholas D., Smyth, Mark J., McCarthy, James and Engwerda, Christian R. (2018). Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection. Clinical and Translational Immunology, 7 (1) e1003, e1003. doi: 10.1002/cti2.1003

  • Souza-Fonseca-Guimaraes, Fernando and Huntington, Nicholas D. (2018). A new checkpoint for Natural Killer cell activation. Immunology and Cell Biology, 96 (1), 5-7. doi: 10.1111/imcb.1027

  • Gao, Yulong, Souza-Fonseca-Guimaraes, Fernando, Bald, Tobias, Ng, Susanna S., Young, Arabella, Ngiow, Shin Foong, Rautela, Jai, Straube, Jasmin, Waddell, Nic, Blake, Stephen J., Yan, Juming, Bartholin, Laurent, Lee, Jason S., Vivier, Eric, Takeda, Kazuyoshi, Messaoudene, Meriem, Zitvogel-, Laurence, Teng, Michele W. L., Belz, Gabrielle T., Engwerda, Christian R., Huntington, Nicholas D., Nakamura, Kyohei, Hoelzel, Michael and Smyth, Mark J. (2017). Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nature Immunology, 18 (9), 1004-1015. doi: 10.1038/ni.3800

  • Putz, Eva M., Mayfosh, Alyce J., Kos, Kevin, Barkauskas, Deborah S., Nakamura, Kyohei, Town, Liam, Goodall, Katharine J., Yee, Dean Y., Poon, Ivan K. H., Baschuk, Nikola, Souza-Fonseca-Guimaraes, Fernando, Hulett, Mark D. and Smyth, Mark J. (2017). NK cell heparanase controls tumor invasion and immune surveillance. Journal of Clinical Investigation, 127 (7), 2777-2788. doi: 10.1172/JCI92958

  • Souza-Fonseca-Guimaraes, Paulo, Guimaraes, Fernando, de Souza-Araujo, Caroline Natânia, Leite, Lidiane Maria Boldrini, Senegaglia, Alexandra Cristina, Nishiyama, Anita and Souza-Fonseca-Guimaraes, Fernando (2017). Natural killer cell assessment in peripheral circulation and bronchoalveolar lavage fluid of patients with severe sepsis: a case control study. International Journal of Molecular Sciences, 18 (3) 616, 616. doi: 10.3390/ijms18030616

  • Lönnberg, Tapio, Svensson, Valentine, James, Kylie R., Fernandez-Ruiz, Daniel, Sebina, Ismail, Montandon, Ruddy, Soon, Megan S. F., Fogg, Lily G., Nair, Arya Sheela, Liligeto, Urijah N., Stubbington, Michael J. T., Ly, Lam-Ha, Bagger, Frederik Otzen, Zwiessele, Max, Lawrence, Neil D., Souza-Fonseca-Guimaraes, Fernando, Bunn, Patrick T., Engwerda, Christian R., Heath, William R., Billker, Oliver, Stegle, Oliver, Haque, Ashraful and Teichmann, Sarah A. (2017). Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves TH1/TFHfate bifurcation in malaria. Science Immunology, 2 (9) eaal2192, eaal2192. doi: 10.1126/sciimmunol.aal2192

  • Viant, Charlotte, Guia, Sophie, Hennessy, Robert J., Rautela, Jai, Pham, Kim, Bernat, Claire, Goh, Wilford, Jiao, Yuhao, Delconte, Rebecca, Roger, Michael, Simon, Vanina, Souza-Fonseca-Guimaraes, Fernando, Grabow, Stephanie, Belz, Gabrielle T., Kile, Benjamin T., Strasser, Andreas, Gray, Daniel, Hodgkin, Phillip D., Beutler, Bruce, Vivier, Eric, Ugolini, Sophie and Huntington, Nicholas D. (2017). Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival. Journal of Experimental Medicine, 214 (2), 491-510. doi: 10.1084/jem.20160869

  • Bunting, Mark D., Varelias, Antiopi, Souza-Fonseca-Guimaraes, Fernando, Schuster, Iona S., Lineburg, Katie E., Kuns, Rachel D., Fleming, Peter, Locke, Kelly R., Huntington, Nicholas D., Blazar, Bruce R., Lane, Steven W., Tey, Siok-Keen, MacDonald, Kelli P. A., Smyth, Mark J., Degli-Esposti, Mariapia A. and Hill, Geoffrey R. (2017). GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood, 129 (5), 630-642. doi: 10.1182/blood-2016-08-734020

  • Sebina, Ismail, James, Kylie R., Soon, Megan S. F., Fogg, Lily G., Best, Shannon E., Labastida Rivera, Fabian de, Montes de Oca, Marcela, Amante, Fiona H., Thomas, Bryce S., Beattie, Lynette, Souza-Fonseca-Guimaraes, Fernando, Smyth, Mark J., Hertzog, Paul J., Hill, Geoffrey R., Hutloff, Andreas, Engwerda, Christian R. and Haque, Ashraful (2016). IFNAR1-signalling obstructs ICOS-mediated humoral immunity during non-lethal blood-stage Plasmodium infection. PLoS Pathogens, 12 (11) e1005999, e1005999. doi: 10.1371/journal.ppat.1005999

  • Le Texier, Laetitia, Lineburg, Katie E., Cao, Benjamin, McDonald-Hyman, Cameron, Leveque-El Mouttie, Lucie, Nicholls, Jemma, Melino, Michelle, Nalkurthi, Blessy C., Alexander, Kylie A., Teal, Bianca, Blake, Stephen J., Souza-Fonseca-Guimaraes, Fernando, Engwerda, Christian R., Kuns, Rachel D., Lane, Steven W., Teng, Michele, Teh, Charis, Gray, Daniel, Clouston, Andrew D., Nilsson, Susan K., Blazar, Bruce R., Hill, Geoffrey R. and MacDonald, Kelli P. A. (2016) Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease. JCI Insight, 1 15: . doi:10.1172/jci.insight.86850

  • Souza-Fonseca-Guimaraes, Fernando, Blake, Stephen J., Makkouk, Amani, Chester, Cariad, Kohrt, Holbrook E. and Smyth, Mark J. (2016). Anti-CD137 enhances anti-CD20 therapy of systemic B-cell lymphoma with altered immune homeostasis but negligible toxicity. OncoImmunology, 5 (7) e1192740, e1192740. doi: 10.1080/2162402X.2016.1192740

  • Souza-Fonseca-Guimaraes, F., Krasnova, Y., Putoczki, T., Miles, K., MacDonald, K. P., Town, L., Shi, W., Gobe, G. C., McDade, L., Mielke, L. A., Tye, H., Masters, S. L., Belz, G. T., Huntington, N. D., Radford-Smith, G. and Smyth, M. J. (2016). Granzyme M has a critical role in providing innate immune protection in ulcerative colitis. Cell Death and Disease, 7 (7) e2302, e2302-e2302. doi: 10.1038/cddis.2016.215

  • Souza-Fonseca-Guimaraes, Fernando (2016). NK cell-based immunotherapies: awakening the innate anti-cancer response. Discovery Medicine, 21 (115), 197-203.

  • Viel, Sebastien, Marcais, Antoine, Guimaraes, Fernando Souza-Fonseca, Loftus, Roisin, Rabilloud, Jessica, Grau, Morgan, Degouve, Sophie, Djebali, Sophia, Sanlaville, Amelien, Charrier, Emily, Bienvenu, Jacques, Marie, Julien C., Caux, Christophe, Marvel, Jacqueline, Town, Liam, Huntington, Nicholas D., Bartholin, Laurent, Finlay, David, Smyth, Mark J. and Walzer, Thierry (2016). TGF-beta inhibits the activation and functions of NK cells by repressing the mTOR pathway. Science Signaling, 9 (415) ra19, ra19-ra19. doi: 10.1126/scisignal.aad1884

  • Trojan, P. J.J., Bohatch-Junior, M. S., Otuki, M. F., Souza-Fonseca-Guimarães, F., Svidnicki, P. V., Nogaroto, V., Fernandes, D., Krum, E. A. and Favero, G. M. (2016). Pravastatina induz parada no ciclo celular e diminuição na produção de VEGF e bFGF em linhagem de mieloma multiplo. Brazilian Journal of Biology, 76 (1), 59-65. doi: 10.1590/1519-6984.11914

  • Krasnova, Yelena, Putz, Eva Maria, Smyth, Mark J. and Souza-Fonseca-Guimaraes, Fernando (2015). Bench to bedside: NK cells and control of metastasis. Clinical Immunology, 177, 50-59. doi: 10.1016/j.clim.2015.10.001

  • Souza-Fonseca-Guimaraes, Fernando, Young, Arabella, Mittal, Deepak, Martinet, Ludovic, Bruedigam, Claudia, Takeda, Kazuyoshi, Andoniou, Christopher E., Degli-Esposti, Mariapia A., Hill, Geoffrey R. and Smyth, Mark J. (2015). NK cells require IL-28R for optimal in vivo activity. Proceedings of the National Academy of Sciences of the United States of America, 112 (18), E2376-E2384. doi: 10.1073/pnas.1424241112

  • Martinet, Ludovic, FerrariDeAndrade, Lucas, Guillerey, Camille, Lee, Jason S, Liu, Jing, Souza-Fonseca-Guimaraes, Fernando, Hutchinson, Dana S, Kolesnik, Tatiana B, Nicholson, Sandra E, Huntington, Nicholas D and Smyth, Mark J (2015). DNAM-1 Expression Marks an Alternative Program of NK Cell Maturation. Cell Reports, 11 (1), 85-97. doi: 10.1016/j.celrep.2015.03.006

  • Paget, C., Chow, M. T., Gherardin, N. A., Beavis, P. A., Uldrich, A. P., Duret, H., Hassane, M., Souza-Fonseca-Guimaraes, F., Mogilenko, D. A., Staumont-Salle, D., Escalante, N. K., Hill, G. R., Neeson, P., Ritchie, D. S., Dombrowicz, D., Mallevaey, T., Trottein, F., Belz, G. T., Godfrey, D. I. and Smyth, M. J. (2015). CD3 bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+T cells. Immunology and Cell Biology, 93 (2), 198-212. doi: 10.1038/icb.2014.94

  • Souza-Fonseca-Guimaraes, Fernando, Young, Arabella and Smyth, Mark J. (2015). IFN type III: In vivo NK cell response. Oncotarget, 6 (24), 19960-19961. doi: 10.18632/oncotarget.4758

  • Sathe, Priyanka, Delconte, Rebecca B., Souza-Fonseca-Guimaraes, Fernando, Seillet, Cyril, Chopin, Michael, Vandenberg, Cassandra J., Rankin, Lucille C., Mielke, Lisa A., Vikstrom, Ingela, Kolesnik, Tatiana B., Nicholson, Sandra E., Vivier, Eric, Smyth, Mark J., Nutt, Stephen L., Glaser, Stefan P., Strasser, Andreas, Belz, Gabrielle T., Carotta, Sebastian and Huntington, Nicholas D. (2014). Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nature Communications, 5 (1) 4539, 1-10. doi: 10.1038/ncomms5539

  • Parlato, Marianna, Souza-Fonseca-Guimaraes, Fernando, Philippart, François, Misset, Benoît, Adib-Conquy, Minou and Cavaillon, Jean-Marc (2014). CD24-triggered caspase-dependent apoptosis via mitochondrial membrane depolarization and reactive oxygen species production of human neutrophils is impaired in sepsis. Journal of Immunology, 192 (5), 2449-2459. doi: 10.4049/jimmunol.1301055

  • Adib-Conquy, Minou, Scott-Algara, Daniel, Cavaillon, Jean-Marc and Souza-Fonseca-Guimaraes, Fernando (2014). TLR-mediated activation of NK cells and their role in bacterial/viral immune responses in mammals. Immunology and Cell Biology, 92 (3), 256-262. doi: 10.1038/icb.2013.99

  • Chan, Christopher J., Martinet, Ludovic, Gilfillan, Susan, Souza-Fonseca-Guimaraes, Fernando, Chow, Melvyn T., Town, Liam, Ritchie, David S., Colonna, Marco, Andrews, Daniel M. and Smyth, Mark J. (2014). The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nature Immunology, 15 (5), 431-438. doi: 10.1038/ni.2850

  • Souza-Fonseca-Guimaraes, Fernando, Cavaillon, Jean-Marc and Adib-Conquy, Minou (2013). Bench-to-bedside review: natural killer cells in sepsis - guilty or not guilty?. Critical Care, 17 (4) 235 doi: 10.1186/cc12700

  • Souza-Fonseca-Guimaraes, Fernando and Smyth, Mark J. (2013). In the spotlight: myeloid TGF-beta responsiveness promotes metastases. Cancer Discovery, 3 (8), 846-848. doi: 10.1158/2159-8290.CD-13-0271

  • Souza-Fonseca-Guimaraes, Fernando, Parlato, Marianna, De Oliveira, Rosane B., Golenbock, Douglas, Fitzgerald, Katherine, Shalova, Irina N., Biswas, Subhra K., Cavaillon, Jean-Marc and Adib-Conquy, Minou (2013). Interferon-γ and granulocyte/monocyte colony-stimulating factor production by natural killer cells involves different signaling pathways and the adaptor stimulator of interferon genes (STING). Journal of Biological Chemistry, 288 (15), 10715-10721. doi: 10.1074/jbc.M112.435602

  • Souza-Fonseca-Guimaraes, Fernando, Parlato, Marianna, Philippart, François, Misset, Benoît, Cavaillon, Jean-Marc, Adib-Conquy, Minou, Jacqmin, Sébastien, Journois, Didier, Lagrange, Alix, de Villechenon, Gabrielle Pinot, Aissaoui, Nadia, Diehl, Jean-Luc, Guerot, Emmanuel, Venot, Marion, Hamzaoui, Olfa, Prat, Dominique, Sztrymf, Benjamin, Maxime, Djillali Annane Virginie, Polito, Andrea, Bournaud, Elsa, Bruel, Cédric, Fournier, Julien, Garrouste-Orgeas, Maïté, Gregoire, Charles, Lau, Nicolas, Max, Adeline, Bouhemad, Belaïd, Ethuin, Frédéric, Bedos, Jean-Pierre ... Moucadel, Virginie (2012). Toll-like receptors expression and interferon-γ production by NK cells in human sepsis. Critical Care, 16 (5) R206 doi: 10.1186/cc11838

  • Nowatzki, Jenifer, Sene, Reginaldo Vieira, Paludo, Katia Sabrina, Rizzo, Luiz Eduardo, Souza-Fonseca-Guimarães, Fernando, Veiga, Silvio Sanches, Nader, Helena Bonciani, Franco, Célia Regina C. and Trindade, Edvaldo S. (2012). Brown spider (Loxosceles intermedia) venom triggers endothelial cells death by anoikis. Toxicon, 60 (3), 396-405. doi: 10.1016/j.toxicon.2012.04.333

  • Souza-Fonseca-Guimaraes, Fernando, Parlato, Marianna, Fitting, Catherine, Cavaillon, Jean-Marc and Adib-Conquy, Minou (2012). NK cell tolerance to TLR agonists mediated by regulatory T cells after polymicrobial sepsis. Journal of Immunology, 188 (12), 5850-5858. doi: 10.4049/jimmunol.1103616

  • Kuczera, Diogo, Paro de Oliveira, Heloísa Helena, Fonseca Guimarães, Fernando de Souza, de Lima, Carina, Alves, Luciana, Machado, Andressa Franzói, Coelho, Isabela, Yamaguchi, Adriana, Donatti, Lucélia, Naliwaiko, Katya, Fernandes, Luiz Claudio and Nunes, Everson Araújo (2012). Bax/Bcl-2 protein expression ratio and leukocyte function are related to reduction of Walker-256 tumor growth after β-hydroxy-β-methylbutyrate (HMB) administration in Wistar rats. Nutrition and Cancer, 64 (2), 286-293. doi: 10.1080/01635581.2012.647229

  • Rauh, Laryssa K., Horinouchi, Cíntia D.S., Loddi, Alliete M.V., Pietrovski, Evelise F., Neris, Rosalina, Souza-Fonseca-Guimarães, Fernando, Buchi, Dorly F., Biavatti, Maique W., Otuki, Michel F. and Cabrini, Daniela A. (2011). Effectiveness of Vernonia scorpioides ethanolic extract against skin inflammatory processes. Journal of Ethnopharmacology, 138 (2), 390-397. doi: 10.1016/j.jep.2011.09.012

  • Souza-Fonseca-Guimaraes, Fernando, Adib-Conquy, Minou and Cavaillon, Jean-Marc (2011). Natural killer (NK) cells in antibacterial innate immunity: angels or devils?. Molecular Medicine, 18 (1), 270-285. doi: 10.2119/molmed.2011.00201

  • de Oliveira, Carolina C., Abud, Ana P. R., de Oliveira, Simone M., de SF Guimarães, Fernando, de Andrade, Lucas F., Di Bernardi, Raffaello P., de O Coletto, Ediely L., Kuczera, Diogo, Da Lozzo, Eneida J., Gonçalves, Jenifer P., da S Trindade, Edvaldo and de F Buchi, Dorly (2011). Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers. BMC Complementary and Alternative Medicine, 11 (1) 101 doi: 10.1186/1472-6882-11-101

  • Pietrovski, Evelise Fernandes, Paludo, Kátia Sabrina, Mendes, Daniel Augusto Gasparin Bueno, de Souza Fonseca Guimarães, Fernando, Veiga, Silvio Sanchez, de Freitas Buchi, Dorly, Fonseca, Raphael Gomes, Zampronio, Aleksander Roberto, Bader, Michael, Pesquero, João Bosco, Ferreira, Juliano, Otuki, Michel Fleith and Cabrini, Daniela Almeida (2011). B1 and B2 kinin receptor participation in hyperproliferative and inflammatory skin processes in mice. Journal of Dermatological Science, 64 (1), 23-30. doi: 10.1016/j.jdermsci.2011.06.016

  • Guimarães, Fernando S.F., Andrade, Lucas F., Martins, Sharon T., Abud, Ana P.R., Sene, Reginaldo V., Wanderer, Carla, Tiscornia, Inés, Bollati-Fogolín, Mariela, Buchi, Dorly F. and Trindade, Edvaldo S. (2010). In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model. BMC Cancer, 10 113 doi: 10.1186/1471-2407-10-113

  • Guimaraes, Fernando De S. F., De Oliveira, Simone M., De Oliveira, Carolina C., Donatti, Lucelia and Buchi, Dorly De Freitas (2009). A shorter fixation protocol for transmission electron microscopy: An alternative to spend less time. Ultrastructural Pathology, 33 (4), 169-174. doi: 10.3109/01913120902889153

  • Noleto, Rafael Bueno, de Fonseca Souza Guimarães, Fernando, Paludo, Katia Sabrina, Vicari, Marcelo Ricardo, Artoni, Roberto Ferreira and Cestari, Marta Margarete (2009). Genome size evaluation in tetraodontiform fishes from the neotropical region. Marine Biotechnology, 11 (6), 680-685. doi: 10.1007/s10126-009-9215-0

  • Ramsdorf, Wanessa A., Guimarães, Fernando de S.F., Ferraro, Marcos V.M., Gabardo, Juarez, Trindade, Edvaldo da Silva and Cestari, Marta Margarete (2009). Establishment of experimental conditions for preserving samples of fish blood for analysis with both comet assay and flow cytometry. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 673 (1), 78-81. doi: 10.1016/j.mrgentox.2008.11.010

Conference Publication

  • Austin, Rebecca, Bywater, Megan, Straube, Jasmin, Cooper, Leanne T., Headlam, Madeleine, Dave, Keyur, Braun, Matthias, Bald, Tobias, Guimaraes, Fernando, Jacquelin, Sebastien, Witkowski, Matthew, Aifantis, Iannis, Hill, Geoffrey R., Smyth, Mark J. and Lane, Steven W. (2018). Oncogenic-Drivers Dictate Immune Responses to Control Disease Progression in Acute Myeloid Leukaemia. 60th Annual Meeting of the American-Society-of-Hematology (ASH), San Diego, CA, United States, 1-4 December 2018. Washington, DC, United States: American Society of Hematology. doi: 10.1182/blood-2018-99-112009

  • Young, A., Souza-Fonseca-Guimaraes, F., Ngiow, S. F., Gao, Y., Linden, J., Huntington, N. D. and Smyth, M. J. (2016). Adenosine impairs the proliferative capacity of terminally mature NK cells. International Congress of Immunology (ICI), Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley - VCH. doi: 10.1002/eji.201670200

  • Kumar, V., Woodruff, T., Ting, M., Boyd, A., Coulthard, M., Souza-Fonseca-Guimaraes, F. and Smyth, M. (2016). EphA2KO mice survive longer in a mouse model of sepsis. International Congress of Immunology (ICI), Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley - VCH. doi: 10.1002/eji.201670200

  • Putz, E. M., Souza-Fonseca-Guimaraes, F., Barkauskas, D. S., Town, L., Hulett, M. D. and Smyth, M. J. (2016). The role of heparanase in NK cell migration and NK cell-mediated tumour surveillance. International Congress of Immunology (ICI), Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley - VCH. doi: 10.1002/eji.201670200

  • Souza-Fonseca-Guimaraes, Fernando, Martinet, Ludovic, Hill, Geoffrey R., Teng, Michele W. L. and Smyth, Mark (2014). Checkpoints and interferons in tumor control. 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society (ICIS), Melbourne, Australia, 26-29 October 2014. doi: 10.1016/j.cyto.2014.07.244

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Background: Despite advances in treatment and earlier detection, cancer is still a main cause of cancer death worldwide. Natural killer (NK) cells are circulating innate lymphocytes that naturally protect against tumor spread (metastasis), and recently showed by our group as dysfunctional in the tumour microenvironment (TME) established by cancers at distant organs for future metastatic spread. Yet, despite knowing that NK cells do control cancer metastasis, our knowledge of how cancer cells evade NK cell control is still very poor. This project aims to examine several immune suppressive pathways that cancers likely manipulate to avoid NK cells and spread. These include factors the transforming growth factor (TGF)-β superfamily that are elevated in the tumor environment. These molecules have great potential to suppress the normally high killing and anti-metastatic activity mediated by NK cells, but to date we still need to elucidate how relatively important each pathway might be.

    Proposed research program: The intrinsic NK cell function under suppressive factors stimulation will be assessed with NK cells purified from mouse spleen (wild type) by cell sorter, and in vitro challenge with activating cytokines and suppressive factors. Aim-1: Which suppressive factor is a major inhibitor of NK cell killing activity? This aim will be screened by killing activity of NK cells versus target tumour cells in co-culture systems. Aim-2: Which suppressive factor is a major inhibitor of NK cell cytokine secretion? This aim will assess NK cell cytokine production by intracellular cytokine (e.g. IFN-gamma) staining (flow cytometry) and secreted IFN-gamma, among others, from culture supernatants (ELISA); Aim-3: What is the cellular signalling status under suppressive conditions? The identification of altered cellular signalling will be screened by intracellular staining of phosphorylated signalling molecules (phosphor(p)-AKT, p-ERK1/2, p-p38, p-phospholipase C-gamma2, p-phosphotyrosine, p-SMAD2,3, p-STAT4, p-STAT5 and p-ZAP70 (PhosphoFlow).

    These experimental tools will determine which is the most important suppressive pathway in inhibiting NK cell functions. Information we obtain from this work will allow us to design rationale approaches to increase NK cell function in personalised immunotherapy approaches.