Dr Ian Parish is a fundamental immunologist with internationally recognised expertise in the negative regulation of T cell function. He completed his PhD at the WEHI, during which he studied the cellular and molecular regulation of peripheral T cell tolerance. He then accepted a postdoctoral position at the Yale School of Medicine, where he focused on T cell differentiation during infection, and developed an interest in why T cell responses become blunted during chronic viral infection. After returning to Australia, he established an independent research program at the ANU aimed at deciphering the molecular pathways that limit T cell function.
He joined the Peter MacCallum Cancer Centre in 2018 and has since established a research team to continue and expand on this theme, with the goal of applying this knowledge to guide innovative immunotherapy approaches for the treatment of cancer. Since arriving at Peter Mac, he has secured over $3 million in research funding as a lead investigator through NHMRC, HFSP, The Volkswagen Foundation and industry support. His research has collectively attracted over 3000 citations from publications featured in high impact journals such as JCI, Nature Communications, PNAS, Immunity, Nature Medicine, Blood, JEM, Cell Reports and Cancer Discovery.
This paper identified EGR2 as a novel transcriptional regulator of CD8+ T cell exhaustion in both tumours and chronic infection. Strikingly, EGR2, which is a known master regulator of T cell anergy, controlled completely different genes in exhaustion. This is the first evidence that exhaustion and anergy are differentially “wired”.
This study showed that contrary to existing paradigms, resting, uncultured and quiescent naïve T cells could be edited by CRISPR. Our reported method is valuable as it enables gene editing in mouse models that were not amenable to previous approaches (e.g. T cell tolerance models).
This paper was the first to demonstrate that the negative regulator NDFIP1 restrains CD8+ T cell differentiation. Notably, NDFIP1 was specifically required to enforce one form of T cell tolerance (anergy) but not a different form of tolerance (deletion). This demonstrates that anergy and deletion are molecularly separable processes.
This study identified a novel gene, ETAA1, that controls effector T cell expansion via prevention of replication stress. Surprisingly, ETAA1 was largely dispensable for protection from replication stress in other cell types. This revealed that T cells are uniquely sensitive to replication stress during division.
This paper showed that exhausted T cells are a key source of immunosuppressive IL-10 in chronic viral infection, with IL-10 expression induced by the transcription factor BLIMP-1 downstream of chronic TCR signalling. This in turn identified a novel feedback loop in which exhausted T cells self-regulate by IL-10 production.