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Mackay Lab research

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About Professor Charles Mackay

Charles Mackay did his PhD at Melbourne University, and worked at the Basel Institute for Immunology, LeukoSite Inc. and Millennium Therapeutics in Boston USA, and Garvan Institute in Sydney, before moving to Monash University in mid 2009. Charles Mackay is accomplished in the fields of inflammation, GPCR biology, cell migration and cytokine biology.

Charles is the leading advocate of a new hypothesis to explain many ‘western lifestyle' diseases - that diet, gut microbes and their metabolites are responsible. He is commercialising a new ‘nutraceutical’ approach for the treatment of many human diseases. Charles has produced many monoclonal antibodies over the course of his career, including to the HIV co-receptors CCR5 and CCR3. His other skills include gene transcript profiling, and numerous models of inflammation- asthma, arthritis, type 1 diabetes, colitis, and others.

Charles demonstrated that dietary fibre and its breakdown fermented products, the short chain fatty acids (SCFAs) influence gut homeostasis, the composition of the gut microbiota, immune tolerance, and inflammatory responses. His research focuses on cellular and molecular pathways, such as the metabolite-sensing GPCRs, and epigenetic pathways including HDAC inhibition.

He believes there is considerable potential to manipulate immune responses using 'medicinal foods', as well as novel gut microbial species. He is developing new diets that release very high amounts of beneficial SCFAs in the gastrointestinal tract.

“This is an exciting area for us. People perhaps haven't totally appreciated how connected these major systems are. They influence one another. The microbes that colonise our intestinal tract are a part of this mix. Understanding how diet and the metabolism of dietary substances affect gut microbes and how they affect our immune system is a brand new direction in medical research.”

He says immunologists in the past did not give much credence to prebiotics (beneficial foodstuffs) and probiotics (beneficial microbes) as affecting immune function and inflammatory diseases. These concepts were regarded as being on the fringe of acceptable science. 'That's partly because scientists like to see the molecular mechanisms before they will fully accept new ideas. If you have a phenomenon or an observation and can couple that with a molecule or gene, then you can see the entire picture.'

Charles was ranked a Highly Cited (HiCi) Researcher by Clarivate Analytics in both 2017 and 2018, and was also highly cited from 2005 to 2010 under what was then the ISI citation. A list of the world’s most impactful scientific researchers, the ranking is formed from an estimated two million-plus papers. HiCi researchers are among an exclusive list of scientists globally whose papers are in the top 1% of most cited works in their field.


Our research

Current projects

  1. GPR65, a receptor that explains asthma, IBD and allergy
  2. Medicinal food diet to manipulate the microbiome and treat western lifestyle diseases
  3. The ‘Nutrition-microbiome-physiology axis’ and mechanisms- epigenetics and GPCRs

Visit Professor Mackay's Monash research profile to see a full listing of current projects.

Research activities

Metabolite-sensing GPCRs

The interaction between the body's immune and metabolic systems is another major area of research that Charles is leading at Clayton. Charles is a leader in the field of metabolite-sensing GPCRs, receptors that play dual roles in immune responses and metabolism. Charles published on the relevance of the main receptor characterised to date, GPR43 (Maslowski et al Nature 2009). His main interest currently is GPR65, which he believes is fundamental for barrier homeostasis (gut, skin and lung).

Charles believes that the incidence of diabetes, cardiovascular disease, allergies and asthma, and auto-immune diseases in Western countries relate to a changing diet. Reduced fibre and fish, increased processed foods and resulting obesity has altered the mix of microbes and the things they produce. All this changes our immune system, gut homeostasis and the regulation of inflammatory responses.

Leukocyte trafficking through the body

Charles has received international recognition for major breakthroughs in understanding the role of white blood cells and how they move around the body (see review, Von Andrian and Mackay, NEJM 2000). This work has also led to new understanding on how Human Immunodeficiency Virus (HIV) infects cells. His more recent research into leukocyte traffic to inflamed tissues has resulted in the development of a new antibody treatment (anti-C5aR), now in human clinical trials. Charles is an expert on chemokines and their receptors and is exploring the biological roles of receptors such as CXCR7, CCR6 and CXCR3.

Figure 1: Diet determines gut microbiota composition, and bacterial metabolites underlie numerous “western lifestyle” diseases


Collaborations

We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).


Student research projects

The Mackay Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.