1985 BHB University Of Auckland (NZ)
1988 MBChB University Of Auckland (NZ)
1996 FRCPA Royal College of Pathologists of Australasia
1996-1999 Research Associate, Harvard University, Dana-Farber Cancer Institute, Boston (USA)
1997 FRACP Royal Australasian College of Physicians
2001 MD University Of Auckland (NZ)
1999-2018 NHMRC Fellow, Brisbane (AUS)
Dr. Hill’s work spans basic discovery research and clinical practice in the areas of donor (allogeneic) hematopoietic stem cell transplantation (HCT) and cancer immunotherapy. An author on more than 175 scientific papers, his studies have addressed the major limitations of bone marrow transplantation, namely graft-versus-host disease (GVHD), opportunistic infection, relapse and graft rejection. His studies of cytomegalovirus (CMV) produced the first models of CMV reactivation after allogeneic HCT that allow preclinical testing of strategies to improve anti-viral immunity. Early on, he helped demonstrate the relationship between doses of pre-transplant ‘conditioning’ therapy and GVHD, which led to the use of ‘reduced intensity’ conditioning in nearly half of all HCT performed today. His immunology laboratory especially focuses on the interactions between various ‘cytokine’ molecules, which convey signals between cells, and the multiple types of immune cells that play critical roles in HCT outcomes. They were among the first to show the immunomodulatory effects of stem cells mobilization with the growth-stimulating factor, G-CSF, and more than 80% of HCT now uses G-CSF mobilized stem cells.
On the other hand, based on findings that GVHD can be exacerbated following treatment with this cytokine, G-CSF is now avoided early after HCT. Dr. Hill and colleagues showed that the cytokine, TNF, could induce GVHD; now, anti-TNF antibodies (Enbrel) are routinely used in patients undergoing HCT. More recently, Dr. Hill and colleagues demonstrated a critical role for the IL-6 growth factor in inducing acute GVHD and the ability of an anti-IL-6R antibody to prevent disease in both preclinical and clinical studies. A multi-center Australian phase III study has now completed and extended to explore effects of mucosal cytokines on the gastrointestinal microbiome and GVHD.
Other ongoing studies focus on cytokines that might enhance the anti-tumor efficacy of HCT, focusing on interferons. These factors act upon various cell types that impact HCT outcomes and are now the focus of newer ‘immunotherapies.’ Beyond the immune ‘cytotoxic’ T cells that can attack and kill cancers, Dr. Hill studies the ‘antigen presenting’ cells that instruct donor T cells to generate immune responses to both GVHD target tissues and tumor cells in an effort to separate these detrimental and beneficial responses. His group also studies ‘regulatory’ T cells that can be used to reduce GVHD after HCT and may be modulated to improve efficacy and/or reduce toxicity after cell-based immunotherapies. Finally, Dr. Hill’s group is in the late stages of therapeutic development of strategies that inhibit an immune cell-derived factor (perforin) in order to eliminate graft rejection.
Dr. Hill is a hematologist and an expert in hematopoietic stem cell transplantation and cancer immunotherapy with a particular interest in graft-versus-host disease. He is the Director of Hematopoietic Stem Cell Transplantation at the Seattle Cancer Care Alliance.