Institute of Cellular Medicine

Staff Profile

Professor Andrew Mellor

Prof of Translational Immunology

Background

I earned my PhD in the field of protein biosynthesis from Kings College, London while working on DNA tumor viruses at the Imperial Cancer Research Fund (1973-1976). During my postdoctoral training with Richard Flavell (1979-1984) at the National Institute for Medical Research (London) and Biogen Inc. (Boston) I cloned and sequenced mouse MHC class I genes,uncovered the genetic basis for MHC polymorphism and developed methods to transfect and express MHC genes into cells. In my first academic position (NIMR, 1984-1995) I continued to focus on MHC molecular genetics and developed new interests in studying peripheral tolerance mechanisms using MHC transgenic mice.

In 1995 I moved to the Medical College of Georgia (Augusta GA). In 1998, we reported the seminal discovery that fetal survival during pregnancy depends on regulation of maternal T cell immunity by the enzyme indoleamine 2,3 dioxygenase (IDO). This finding established a new paradigm in understanding how T cell regulation occurs at sites of inflammation by identifying tryptophan catabolism as a critical metabolic process regulating T cell immunity. My laboratory has worked on IDO ever since with major focus on identifying inflammatory pathways that stimulate IDO expression in dendritic cells and elucidating biochemical pathways that suppress T cell responses and activate regulatory T cells.

Another major goal is to develop new strategies and reagents to manipulate IDO activity for clinical benefit in a range of diseases that afflict many people, including cancer, chronic infections, autoimmune syndromes and transplant rejection. While IDO protects healthy tissues from immune attack, it also protects cancerous and infected tissues from attack, requiring IDO inducers and IDO inhibitors to manipulate inflammatory disease processes for clinical benefit. Based on our research, a proprietary IDO inhibitor (IndoximodTM) is under scrutiny in Phase II trials as a potential immune checkpoint blockade inhibitor in cancer patients. In addition, we have developed novel IDO-inducing reagents that prevent and alleviate autoimmune syndromes in mouse models of autoimmune diabetes, multiple sclerosis and rheumatoid arthritis.

In 2015 I moved to the Institute of Cellular Medicine at Newcastle University.  Current research goals are to evaluate the role of nucleic acid sensing pathways in regulating autoimmunity and promoting tumourigenesis, developing novel immunotherapies by manipulating IDO, and elucidating how IDO enhances pain, a common co-morbidity associated with many chronic inflammatory syndromes of clinical importance

Research

Tissue inflammation occurs during infections, cancer, autoimmune, allergic, cardiovascular and neurodegenerative syndromes, pregnancy, transplant rejection and following tissue wounding, burns and exposure to ionizing and ultra-violet radiation.

Inflammation is a complex physiologic phenomenon that can only be studied in whole organisms. Inflammation may initiate or inhibit immune responses contingent on many genetic, environmental and contextual factors.

Our research focuses on the role of the enzyme indoleamine 2,3 dioxygenase (IDO) in inflammatory disease and immunotherapies to treat them. We discovered that IDO protects foetal tissues during pregnancy. IDO also suppresses immunity that destroys healthy tissues but may cause morbidities associated with some chronic diseases such as pain and behavioural disorders.

IDO is induced by interferons type I (IFNalpha/beta) and II (IFNgamma). IDO catabolizes the amino acid tryptophan (Trp) to suppress T cell responses and protect tissues from immune-mediated damage. However some pathogens and tumours hijack the IDO pathway, allowing them to persist and cause chronic infections and cancer in immune competent individuals.

Our research objectives are to understand how altered Trp metabolism potentiates or regulates disease progression before clinical presentation and to apply this knowledge for clinical benefit by manipulating the IDO pathway using novel immunotherapies.


Publications