Mr Frank Vari

Research Officer

The University of Queensland Diamantina Institute
Faculty of Medicine
f.vari1@uq.edu.au
+61 7 344 37060

Overview

A varied career following his interests and surviving, as best as is possible, the vagaries of funding. Completing B.Sc (hons) Hons at the University of Adelaide in Prof Ieva Kotlarski's laboratory, working on mechanisms to overcome tolerance to allogeneic tumours. After leaving Adelaide he headed to Brisbane, which has been my base ever since. Joining the Australian Equine Blood Typing Research Laboratory headed by Dr Kevin Bell, in 1987, working as a research assistant unitl 1989. That year doing PhD studies on the Equine MHC at the Australian Blood Typing Research Laboratories at UQ. In 1995 he moved to the Transplantation biology unit, headed by Ann Kelso, at the QIMR, in Prof Naoshi Kamada's laboratory studying mechansims of liver mediated immunosuppression in a spontaneously tolerising model of orthotopic rat liver transplantation. When funding ran out and that laboratory disbanded I took a tenure track faculty position at the University of Utah in Salt Lake City, USA, in Dr Tom Fuller's lab. Here I worked on studies of cross reactive epitope groups shared by class I MHC molecules and presented by class II MHC antigens in allograft rejection. During this time I received some training in managing a tissue typing laboratory, which was just awful. In 1999, on returning to Brisbane, he finally entered the world of clinical immunotherapy, which was always his burning interest, with Andrew Nichol at QIMR/UQ based in the Clinical Sciences building RBH, working on Dendritic cell based approaches to immunotherapy of chronic myeloid leukaemia, Renal Cell Carcinoma and melanoma. In 2001, after less than spectacular success, I joined the biotech start-up company Alchemia Pty Ltd as a biochemist testing carbohydrate based drugs and designing novel vaccines. This included a due diligence component, which was a different and challenging way of looking at the world of science. In early 2003, after Alchemia re-assessed their priorities for wet lab requirements. I joined the MMRI in 2003, as a team leader responsible for a project on Clinical DC immunotherapy of Myeloma and Prostate Cancer with Prof Derek Hart, a world authority on dendritic cells at the Mater Medical Research Institute. The focus of these studies was strictly translational with a focus of getting the products of cell separation into patients. There was a major focus on GMP quality production of cell therapy products. For three years I was an active member, and for a year the chair of the scientific sub-committee of the Mater HREC. In 2009, I moved to a position with Prof Maher Gandhi, at the Queensland Institute of Medical Research, then, in 2013 moving to the School of Medicine at the University of Queensland based at the Translational Research Institute. In 2014 the group moved to the UQ's Diamantina Institute to continue its work and become the Leukaemia Foundation Blood Cancer Laboratory. During my time with Prof Gandhi's group I have worked on a clinical study of T-cell immunotherapy in EBV+ve non-Hodgkin’s lymphoma. In the laboratory based studies, using clinical material, studies of the immune microenvironment in diffuse large B-cell lymphoma especially the role of circulating monocytes and enhancing mechanisms of killing of blood cancers by natural Killer cells by utilising the unfolded protein response pathway.

Research Interests

  • CD163 identifies a highly immunosuppressive subset of moMDSC in poor-risk diffuse large B-cell lymphoma
    In diffuse large B-cell lymphoma (DLBCL), raised monocyte and low lymphocyte blood counts are associated with inferior outcome. This is believed to be mediated by suppression of effector (NK and T) lymphocytes by CD14+HLA-DRlo monocytoid-myeloid derived suppressor cells (moMDSC), but has not been prospectively validated. Intra-tumoral CD163 expression (a M2 tumor associated macrophage marker) also appears prognostically adverse. The relationship between CD163 and moMDSC, and their influence on antiCD20 monoclonal antibody NK-cell antibody-dependent cellular-cytotoxicity (ADCC) in DLBCL is unknown.
  • Natural Killer cell effector function
    Although Natural killer (NK) cells are key innate immune effectors, the underlying molecular mechanisms controlling their function are poorly understood. NK cells also release cytokines that are important in stimulating and regulating an effector immune response, of which interferon gamma (IFNγ) is the best characterized. In addition to its direct effects on inhibiting viral replication, IFNγ has important effects on macrophages and T-cells, inducing their enhanced function. Modulating NK cell function, through drugs which influence the unfolded protein response, may improve their anti-cancer activity and lead to novel approaches for eradicated NK-susceptible tumours.

Publications

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Supervision

  • Doctor Philosophy

  • Master Philosophy

  • (2009) Doctor Philosophy

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Publications

Journal Article

Conference Publication

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Associate Advisor

  • Master Philosophy — Associate Advisor

    Other advisors:

Completed Supervision