Associate Professor Georgina Clark

Group Leader, Dendritic Cell Research, ANZAC Research InstituteSenior Research Fellow
The University of Sydney School of Medicine

Telephone +61 2 9767 9822
Fax +61 2 9767 9101

Website Dendritic Cell Research

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Biographical details

I lead the Dendritic Cell Research Group based at the ANZAC Research Institute at the Concord Repatriation General Hospital campus. I am a molecular immunologist with a special interest in the development of therapeutic monoclonal antibodies to human myeloid and dendritic cell surface molecules.

I began my research career completing both an honours degree (1983) and PhD (1988) at the Research Centre for Cancer and Transplantation Associate at the University of Melbourne with Professor Ian McKenzie, Dr Nick Deacon and Dr Claudia Mickelson. My early studies focused on cloning cell surface molecules to mouse leucocytes in which I isolated and characterised the cDNAs for mouse CD44 in my honours year and mouse CD4 during my PhD at a time when molecular biology was in its infancy.

Following my PhD, I undertook postdoctoral studies in the Nuffield Department of Surgery at Oxford University with Professor Maggie Dallman (1989). The studies were focused on understanding tolerance induction to improve outcomes for kidney transplant patients. The laboratory was able to use preclinical rat kidney and heart transplant models. I took on the task of cloning the rat CD28 molecule and developing monoclonal antibodies to it with the aim that they would be able to be used therapeutically to regulate tolerance.

After Oxford, I moved to New Zealand to become a research fellow at the Canterbury Health Laboratories in Christchurch and later the University of Otago’s Christchurch Medical School (1993). I worked alongside Professor Derek Hart developing monoclonal antibodies to human dendritic cells. I undertook studies that lead to the identification of the CD300 family of molecules with the characterization of the inhibitory receptor CD300a although at the time it was called CMRF-35H.

In 1998, I returned to Australia to join Derek in establishing the Mater Medical Research Institute as a Research Fellow. As the first senior scientist employed at the MMRI, I learned the difficulties of what it takes to build an internationally renowned institute from the ground up. We established the Dendritic Cell Biology work which continued a translational focus developing therapeutic monoclonal antibodies for DC vaccination and targeting graft versus host disease as a complication of bone marrow transplantation. I lead the Immunoregulatory Team continuing my studies on the CD300 family, working with HUGO to ensure consistent nomenclature between cell surface protein and gene.

I became a contributor to the Human Leucocyte Differentiation Workshops which are an international collaboration aimed at validating monoclonal antibodies to cell surface molecules. In the HLDA7 workshop (2000), we lead the first Dendritic Cell focused studies which lead to the first description of human blood dendritic cell subsets defined by cell surface phenotypes.

Research interests

Leucocyte Membrane Molecules

I am interested in the molecules on the plasma membranes of human leucocytes, particularly the dendritic cells and other cells of the myeloid lineage. The cell surface landscape provides clues into how each cell interacts with its environment. Regulation of immune cell surface phenotypes is crucial to directing cell interactions. Our group has a long history in describing and developing unique monoclonal antibodies to the molecules on the surface of human dendritic cells. We have characterised a number of human cell surface molecules including the CD300 family or immune regulatory molecules, DC activation molecules such as CD83 and the C-type lectin molecules CD205 and CD302.

Our knowledge of the DC cell surface has provided us with opportunities to harness the power of monoclonal antibodies to investigate the function of specific molecules – including the checkpoint inhibitors, and to use them to develop strategies for cancer immunotherapy.

Papers:Clark et al Trends in Immunology 2009, Ju et al Blood 2008, Lo et al JI 2016, Ju et al JI 2016

Human Dendritic Cell Subsets

Dendritic cells orchestrate the immune response; they stimulate responses to danger signals fighting infections and dampen response to self antigen. When things go awry, DC fail to dampen a response contributing to chronic inflammation and autoimmunity to failing to recognise a neoantigen or tumor antigen resulting in cancers. Immunotherapy approaches using blood DC to vaccinate against cancers has long been thought to have great potential but the many clinical trials in a range of cancers have met limited success. DC are a rare cell population and whilst human peripheral blood provides the most easily accessible human DC, using monocytes to derive a DC like cell “in vitro” has been the preferred source of DC in most clinical trials. Our group has concentrated on understanding the blood DC populations, their sparsity and how best to enrich for them to be able to use the “gold standard” blood DC in clinical trial. We have combined our expertise of the DC cell surface landscape to help identify different functional subpopulations of DC from human blood to ensure that we know which DC population should be targeted for a therapeutic outcome.

Link MacDonald Paper, the surface antigen paper 2018

Strategies to use monoclonal antibodies to DC surface molecules as therapeutics

1. DC Immunotherapy

We have developed a platform for the purification of blood DC from apheresis sample provided by patients that will allow us to trial DC immunotherapy for prostate cancer and glioma. A vaccine will be prepared from blood DC enriched from the patient’s apheresis sample and loaded with tumor antigen in the form of mRNA in a process that will take less than 24 hours. Enough vaccine will be prepared for between 5-10 doses. We are currently working to determine the best antigens to load into the DC. Tumor environments are often immunosuppressive. Combining DC vaccines with checkpoint inhibitors are predicted to enhance the efficacy of DC vaccines and we are determining the best combination.

Papers: Fromm paper, Hsu paper

2. Targeting DC

Whilst purifying DC is one approach to tumour immunotherapy, directly targeting antigen to a DC in vivo would have many advantages. A number of our mAbs target molecules that are expressed primarily by DC, are able to be internalised and are thus potential DC targeting mAbs. We have made chimeric versions of these mAbs to test their efficacy as antigen loading therapeutics.

3. Antibody drug conjugates

Acute Myeloid Leukemia (AML) is an aggressive leukemia with poor overall survival. We have identified a number of mAbs that target molecules expressed on leukemic blast cells from a high percentage of AML patients. We are developing these mAbs into antibody drug conjugates able to deliver toxins specifically to the leukemic cells and investigating strategies to safely use these conjugates without compromising the haematopoietic system of the patient.

Current research students

Project title Research student
Towards a therapeutic vaccine for glioblastoma multiforme. Ben KONG

Associations

Australian Society of Immunology

Sydney Catalyst

Human Leucocyte Differentiation Anitgens

Selected grants

2017

  • Therapeutic Antibody Translation into Patients; Clark G, Ho P, Larsen S, Horvath L; Cancer Institute NSW/Translational Program Grant.

2016

  • Development of a New Specific Immunosuppressive Monoclonal Antibody to Advance Transplantation; Hogarth P, Clark G, Gray P, Fazekas de St Groth B, Larsen S, Gottlieb D, Alexander S, Hennessy A, Hart D; National Health and Medical Research Council (NHMRC)/Development Grants.

2013

  • Automacs Pro Seperator; Hart D, Handelsman D, Le Couteur D, Nicholson G, Kritharides L, Zhou H, Clark G, Kennerson M, Allan C, Walters K, Cogger V, Simanainen U, Zheng Y, Seibel M; DVC Research/Equipment Grant.
  • IVIS Lumina II in vivo Imaging System; Seibel M, Handelsman D, Le Couteur D, Hart D, Nicholson G, Freedman B, Kritharides L, Jessup W, Zhou H, Clark G, Kennerson M, Allan C, Walters K, Cogger V, McMahon A, Simanainen U, Kockx M, Speranza T, Zheng Y; DVC Research/Equipment Grant.

2011

  • MOLECULAR IMAGER CHEMIDoc XRS SYSTEM & MINI P ROTEAN GEL/TRANSBLOT Cell SYSTEM (BIO-RAD. AUSTRALIA; Allan C, Handelsman D, Zhou H, Seibel M, Kennerson M, Nicholson G, Blair I, Le Couteur D, McMahon A, Hart D, Clark G, Simanainen U; National Health and Medical Research Council (NHMRC)/Equipment Grants.

Selected publications

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Journals

  • Hsu, J., Bryant, C., Papadimitrious, M., Kong, B., Gasiorowski, R., Orellana, D., McGuire, H., Fazekas de St Groth, B., Joshua, D., Ho, P., Iland, H., Gibson, J., Clark, G., Fromm, P., Hart, D., et al (2018). A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission. OncoImmunology, 7(4), e1419114-1-e1419114-11. [More Information]
  • Li, Z., Ju, X., Lee, K., Clarke, C., Hsu, J., Abadir, E., Bryant, C., Pears, S., Sunderland, N., Heffernan, S., Lo, T., Fromm, P., Silveira, P., Cooper, W., Brown, C., Clark, G., Hart, D., et al (2018). CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma. Haematologica, 103(4), 655-665. [More Information]
  • Bryant, C., Fromm, P., Kupresanin, F., Clark, G., Lee, K., Clarke, C., Silveira, P., Suen, H., Brown, R., Newman, E., Ho, P., Bradstock, K., Joshua, D., Hart, D., et al (2016). A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset. Immunology and Cell Biology, 94(5), 447-457. [More Information]
  • Fromm, P., Kupresanin, F., Brooks, A., Dunbar, P., Haniffa, M., Hart, D., Clark, G. (2016). A multi-laboratory comparison of blood dendritic cell populations. Clinical & Translational Immunology, 5(4), 1-9. [More Information]
  • Lo, T., Silveira, P., Fromm, P., Verma, N., Vu, P., Kupresanin, F., Adam, R., Kato, M., Cogger, V., Clark, G., Hart, D. (2016). Characterization of the expression and function of the C-type lectin receptor CD302 in mice and humans reveals a role in dendritic cell migration. Journal of Immunology, 197(3), 885-898. [More Information]
  • Fromm, P., Papadimitrious, M., Hsu, J., Van Kooten Losio, N., Verma, N., Lo, T., Silveira, P., Bryant, C., Turtle, C., Prue, R., Horvath, L., Bradstock, K., Joshua, D., Clark, G., Hart, D., et al (2016). CMRF-56+ blood dendritic cells loaded with mRNA induce effective antigen-specific cytotoxic T-lymphocyte responses. OncoImmunology, 5(6), 1-12. [More Information]
  • Seldon, T., Pryor, R., Palkova, A., Jones, M., Verma, N., Findova, M., Braet, K., Sheng, Y., Fan, Y., Zhou, E., Fromm, P., Silveira, P., Elgundi, Z., Ju, X., Clark, G., Bradstock, K., Hart, D., et al (2016). Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. Leukemia, 30(3), 692-700. [More Information]
  • Clark, G., Kupresanin, F., Fromm, P., Ju, X., Muusers, L., Silveira, P., Elgundi, Z., Gasiorowski, R., Papadimitrious, M., Bryant, C., Lee, K., Harman, A., Hart, D., et al (2016). New insights into the phenotype of human dendritic cell populations. Clinical & Translational Immunology, 5(1), 1-12. [More Information]
  • Clark, G., Stockinger, H., Balderas, R., van Zelm, M., Zola, H., Hart, D., Engel, P. (2016). Nomenclature of CD molecules from the Tenth Human Leucocyte Differentiation Antigen Workshop. Clinical & Translational Immunology, 5(1), 1-3. [More Information]
  • Ju, X., Silveira, P., Hsu, W., Elgundi, Z., Alingcastre, R., Verma, N., Fromm, P., Hsu, J., Bryant, C., Li, Z., Lo, T., Lee, K., Fazekas de St Groth, B., Larsen, S., Gibson, J., Bradstock, K., Clark, G., Hart, D., et al (2016). The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population. Journal of Immunology, 197(12), 4613-4625. [More Information]
  • Engel, P., Boumsell, L., Balderas, R., Bensussan, A., Gattei, V., Horejsi, V., Jin, B., Malavasi, F., Mortari, F., Schwartz-Albiez, R., Clark, G. (2015). CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology. Journal of Immunology, 195(10), 4555-4563. [More Information]
  • Gasiorowski, R., Clark, G., Bradstock, K., Hart, D. (2014). Antibody therapy for acute myeloid leukaemia. British Journal of Haematology, 164(4), 481-495. [More Information]
  • Gasiorowski, R., Ju, X., Hart, D., Clark, G. (2013). CD300 molecule regulation of human dendritic cell functions. Immunology Letters, 149(1-2), 93-100. [More Information]
  • Ding, Y., Ju, X., Azlan, M., Hart, D., Clark, G. (2011). Screening of the HLDA9 panel on peripheral blood dendritic cell populations. Immunology Letters, 134(2), 161-166. [More Information]
  • Jongbloed, S., Kassianos, A., McDonald, K., Clark, G., Ju, X., Angel, C., Chen, C., Dunbar, P., Wadley, R., jeet, V., Hart, D., et al (2010). Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. The Journal of Experimental Medicine, 207(6), 1247-1260. [More Information]
  • Clark, G., Ju, X., Tate, C., Hart, D. (2009). The CD300 family of molecules are evolutionarily significant regulators of leukocyte functions. Trends in Immunology, 30(5), 209-217. [More Information]
  • Clark, G., Ju, X., Azlan, M., Tate, C., Ding, Y., Hart, D. (2009). The CD300 molecules regulate monocyte and dendritic cell functions. Immunobiology, 214, 730-736. [More Information]
  • Hart, D., Clark, G., Ju, X., Zenke, M. (2008). Cd300a and Cd300c on Plasmacytoid Dendritic Cells Are down-Regulated by Tlr7 and Tlr9 Ligand Induced Type I Interferon. Biology of Blood and Marrow Transplantation, 14(2), 118-118.
  • Ju, X., Zenke, M., Hart, D., Clark, G. (2008). CD300a/c regulate type I interferon and TNF-(alpha) secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands. Blood, 112, 1184-1194. [More Information]
  • Clark, G., Jamriska, L., Rao, M., Hart, D. (2007). Monocytes immunoselected via the novel monocyte specific molecule, CD300e, differentiate into active migratory dendritic cells. Journal of Immunotherapy, 30(3), 303-311. [More Information]
  • Hart, D., Rao, M., Ju, X., Clark, G. (2007). Novel Human CD4+ T Lymphocyte Subpopulations Defined by CD300a/c Molecule Expression. Blood, 110(11), 682a-682a. [More Information]
  • Clark, G., Rao, M., Ju, X., Hart, D. (2007). Novel human CD4+ T lymphocyte subpopulations defined by CD300a/c molecule expression. Journal of Leukocyte Biology, 82(5), 1126-1135. [More Information]
  • Modra, C., Jamriska, L., Rao, M., Clark, G., Hart, D. (2006). MMRI-23: A potential role in AML antibody-mediated therapy. Blood, 108(11), 225b-225b.
  • Modra, C., Radford, K., Gardiner, D., Hart, D., Clark, G. (2005). An inhibitory molecule involved in myeloid and DC differentiation. Tissue Antigens: immune response genetics, 66(5), 494-494.
  • Clark, G., Munster, D., Yusuf, S., Hart, D. (2005). Eighth Leucocyte DiVerentiation Antigen Workshop DC section summary. Cellular Immunology, 236, 21-28. [More Information]
  • Collin, M., Munster, D., Clark, G., Wang, X., Dickinson, A., Hart, D. (2005). In vitro depletion of tissue-derived dendritic cells by CMRF-44 antibody and alemtuzumab: implications for the control of Graft-versus-host disease. Transplantation, 79(6), 722-725. [More Information]
  • Hardy, M., Kassianos, A., Clark, G., Hart, D., Radford, K. (2005). Production of IL-2, IL-12, and IL-10 by human blood myeloid dendritic cells. Tissue Antigens: immune response genetics, 66(5), 437-437.

2018

  • Hsu, J., Bryant, C., Papadimitrious, M., Kong, B., Gasiorowski, R., Orellana, D., McGuire, H., Fazekas de St Groth, B., Joshua, D., Ho, P., Iland, H., Gibson, J., Clark, G., Fromm, P., Hart, D., et al (2018). A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission. OncoImmunology, 7(4), e1419114-1-e1419114-11. [More Information]
  • Li, Z., Ju, X., Lee, K., Clarke, C., Hsu, J., Abadir, E., Bryant, C., Pears, S., Sunderland, N., Heffernan, S., Lo, T., Fromm, P., Silveira, P., Cooper, W., Brown, C., Clark, G., Hart, D., et al (2018). CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma. Haematologica, 103(4), 655-665. [More Information]

2016

  • Bryant, C., Fromm, P., Kupresanin, F., Clark, G., Lee, K., Clarke, C., Silveira, P., Suen, H., Brown, R., Newman, E., Ho, P., Bradstock, K., Joshua, D., Hart, D., et al (2016). A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset. Immunology and Cell Biology, 94(5), 447-457. [More Information]
  • Fromm, P., Kupresanin, F., Brooks, A., Dunbar, P., Haniffa, M., Hart, D., Clark, G. (2016). A multi-laboratory comparison of blood dendritic cell populations. Clinical & Translational Immunology, 5(4), 1-9. [More Information]
  • Lo, T., Silveira, P., Fromm, P., Verma, N., Vu, P., Kupresanin, F., Adam, R., Kato, M., Cogger, V., Clark, G., Hart, D. (2016). Characterization of the expression and function of the C-type lectin receptor CD302 in mice and humans reveals a role in dendritic cell migration. Journal of Immunology, 197(3), 885-898. [More Information]
  • Fromm, P., Papadimitrious, M., Hsu, J., Van Kooten Losio, N., Verma, N., Lo, T., Silveira, P., Bryant, C., Turtle, C., Prue, R., Horvath, L., Bradstock, K., Joshua, D., Clark, G., Hart, D., et al (2016). CMRF-56+ blood dendritic cells loaded with mRNA induce effective antigen-specific cytotoxic T-lymphocyte responses. OncoImmunology, 5(6), 1-12. [More Information]
  • Seldon, T., Pryor, R., Palkova, A., Jones, M., Verma, N., Findova, M., Braet, K., Sheng, Y., Fan, Y., Zhou, E., Fromm, P., Silveira, P., Elgundi, Z., Ju, X., Clark, G., Bradstock, K., Hart, D., et al (2016). Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. Leukemia, 30(3), 692-700. [More Information]
  • Clark, G., Kupresanin, F., Fromm, P., Ju, X., Muusers, L., Silveira, P., Elgundi, Z., Gasiorowski, R., Papadimitrious, M., Bryant, C., Lee, K., Harman, A., Hart, D., et al (2016). New insights into the phenotype of human dendritic cell populations. Clinical & Translational Immunology, 5(1), 1-12. [More Information]
  • Clark, G., Stockinger, H., Balderas, R., van Zelm, M., Zola, H., Hart, D., Engel, P. (2016). Nomenclature of CD molecules from the Tenth Human Leucocyte Differentiation Antigen Workshop. Clinical & Translational Immunology, 5(1), 1-3. [More Information]
  • Ju, X., Silveira, P., Hsu, W., Elgundi, Z., Alingcastre, R., Verma, N., Fromm, P., Hsu, J., Bryant, C., Li, Z., Lo, T., Lee, K., Fazekas de St Groth, B., Larsen, S., Gibson, J., Bradstock, K., Clark, G., Hart, D., et al (2016). The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population. Journal of Immunology, 197(12), 4613-4625. [More Information]

2015

  • Engel, P., Boumsell, L., Balderas, R., Bensussan, A., Gattei, V., Horejsi, V., Jin, B., Malavasi, F., Mortari, F., Schwartz-Albiez, R., Clark, G. (2015). CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology. Journal of Immunology, 195(10), 4555-4563. [More Information]

2014

  • Gasiorowski, R., Clark, G., Bradstock, K., Hart, D. (2014). Antibody therapy for acute myeloid leukaemia. British Journal of Haematology, 164(4), 481-495. [More Information]

2013

  • Gasiorowski, R., Ju, X., Hart, D., Clark, G. (2013). CD300 molecule regulation of human dendritic cell functions. Immunology Letters, 149(1-2), 93-100. [More Information]

2011

  • Ding, Y., Ju, X., Azlan, M., Hart, D., Clark, G. (2011). Screening of the HLDA9 panel on peripheral blood dendritic cell populations. Immunology Letters, 134(2), 161-166. [More Information]

2010

  • Jongbloed, S., Kassianos, A., McDonald, K., Clark, G., Ju, X., Angel, C., Chen, C., Dunbar, P., Wadley, R., jeet, V., Hart, D., et al (2010). Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. The Journal of Experimental Medicine, 207(6), 1247-1260. [More Information]

2009

  • Clark, G., Ju, X., Tate, C., Hart, D. (2009). The CD300 family of molecules are evolutionarily significant regulators of leukocyte functions. Trends in Immunology, 30(5), 209-217. [More Information]
  • Clark, G., Ju, X., Azlan, M., Tate, C., Ding, Y., Hart, D. (2009). The CD300 molecules regulate monocyte and dendritic cell functions. Immunobiology, 214, 730-736. [More Information]

2008

  • Hart, D., Clark, G., Ju, X., Zenke, M. (2008). Cd300a and Cd300c on Plasmacytoid Dendritic Cells Are down-Regulated by Tlr7 and Tlr9 Ligand Induced Type I Interferon. Biology of Blood and Marrow Transplantation, 14(2), 118-118.
  • Ju, X., Zenke, M., Hart, D., Clark, G. (2008). CD300a/c regulate type I interferon and TNF-(alpha) secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands. Blood, 112, 1184-1194. [More Information]

2007

  • Clark, G., Jamriska, L., Rao, M., Hart, D. (2007). Monocytes immunoselected via the novel monocyte specific molecule, CD300e, differentiate into active migratory dendritic cells. Journal of Immunotherapy, 30(3), 303-311. [More Information]
  • Hart, D., Rao, M., Ju, X., Clark, G. (2007). Novel Human CD4+ T Lymphocyte Subpopulations Defined by CD300a/c Molecule Expression. Blood, 110(11), 682a-682a. [More Information]
  • Clark, G., Rao, M., Ju, X., Hart, D. (2007). Novel human CD4+ T lymphocyte subpopulations defined by CD300a/c molecule expression. Journal of Leukocyte Biology, 82(5), 1126-1135. [More Information]

2006

  • Modra, C., Jamriska, L., Rao, M., Clark, G., Hart, D. (2006). MMRI-23: A potential role in AML antibody-mediated therapy. Blood, 108(11), 225b-225b.

2005

  • Modra, C., Radford, K., Gardiner, D., Hart, D., Clark, G. (2005). An inhibitory molecule involved in myeloid and DC differentiation. Tissue Antigens: immune response genetics, 66(5), 494-494.
  • Clark, G., Munster, D., Yusuf, S., Hart, D. (2005). Eighth Leucocyte DiVerentiation Antigen Workshop DC section summary. Cellular Immunology, 236, 21-28. [More Information]
  • Collin, M., Munster, D., Clark, G., Wang, X., Dickinson, A., Hart, D. (2005). In vitro depletion of tissue-derived dendritic cells by CMRF-44 antibody and alemtuzumab: implications for the control of Graft-versus-host disease. Transplantation, 79(6), 722-725. [More Information]
  • Hardy, M., Kassianos, A., Clark, G., Hart, D., Radford, K. (2005). Production of IL-2, IL-12, and IL-10 by human blood myeloid dendritic cells. Tissue Antigens: immune response genetics, 66(5), 437-437.

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