An arsenal of proteins used by many cell types to communicate with and control other cells could hold the answers to treating a multitude of diseases, especially cancer.

The University of Queensland Diamantina Institute’s Dr Andrew Brooks leads a research group based at TRI, focusing on understanding these messenger proteins, known as cytokines, and targeting their receptor sites to treat diseases. The discoveries made by his laboratory could improve patient outcomes for many diseases, including potential new therapeutics for diseases such as leukaemia, melanoma and growth disorder, as well as improving recovery from liver surgery.

• Dr Brooks' research is about the processes that regulate cells and when that goes wrong how it can lead to disease
• He has identified a potential new treatment for liver surgery patients after they discovered that the hormone plays a key role in reducing inflammation and increasing survival rates following liver surgery
• The laboratory at TRI is developing potential therapeutic molecules to target mutant cytokine receptors linked to cancers such as leukaemia and lung cancer

According to Dr Brooks, his team never starts out looking at a specific disease, but rather at understanding fundamental cellular mechanisms.

“We are trying to understand how cytokine receptors transmit signals into cells to drive their growth and metabolism along with how you can activate or inhibit these receptors,” said Dr Brooks.

“We also look at what happens when there are mutations in cytokine receptors and their signalling partners, and how this impacts different diseases,” he said.

“In essence, my research is about the processes that regulate cells and when that goes wrong how it can lead to disease. When the cytokine signalling process goes wrong, there are usually big outcomes.

 “The way I explain our work to people is that I am more like a mechanic. Mechanics want to see how things work; If you understand how to fix an engine in one can, then you can much more easily fix an engine in any model of car. It’s a bit like that with cytokines. A lot of functions and mechanisms are very similar across different cytokines, which makes it easy to transfer discoveries to different diseases, particularly in cancers and the regulation of cell growth.”

Cytokines were discovered in the 1940s, but it took another 50 years before they emerged as an important frontier in medicine for their potential as diagnostic, prognostic and therapeutic agents in human disease.

With more than 100 known cytokines playing roles in nearly every biological process in the body, Dr Brooks focuses on a number of the Class 1 cytokine receptor family including, growth hormone, thrombopoietin, interleukin-6 (IL-6), interleukin-7 (IL-7) and prolactin.

Importantly, through his studies of Growth Hormone, Dr Brooks and his team have identified a potential new treatment for liver surgery patients after they discovered that the hormone plays a key role in reducing inflammation and increasing survival rates following liver surgery.   

“We found that growth hormone induced production of a protein called HLA-G, which suppressed the inflammatory response after surgery. By administering the HLA-G protein to mice deficient in the growth hormone receptor, we were able to reduce inflammation and enable liver regeneration and survival,” Dr Brooks said.

“We expect our study may lead to significant clinical outcomes.”

Their work also raises the possibility of treating liver and other organ transplant patients with the HLA-G protein or growth hormone to help suppress inflammation following surgery and reduce organ rejection rates.

Dr Brooks is also developing potential therapeutic molecules to target mutant cytokine receptors linked to cancers such as leukaemia and lung cancer.

“These molecules are especially exciting because they appear to be very specific and therefore we would expect low side effects as the major effect would only be to cancerous cells with the damaged receptor,” he said.

“We have two molecules we are working on that are definitely promising, but they are still in the early laboratory development phase.

“It takes a lot of research and funding to find and translate these molecules into something that’s going to end up in the clinic and be a very specific targeted approach that targets only one particular disease and has very minimal side effects.”

What are cytokines?

Cytokines are a broad group of small signalling proteins produced by a range of cell types, including immune cells. These proteins act through cell surface receptors and are especially important in regulating many functions such as growth, red blood cell production, and stimulating our immune and inflammation responses. The also play an important role in embryonic development. Malfunctions in cytokine signalling have been linked to a range of diseases, cancers and autoimmune diseases, schizophrenia, Alzheimer’s disease and depression.

About Professor Brooks

Dr Andrew Brooks is the Group Leader of the Cytokine Receptor Signalling Group at The University of Queensland Diamantina Institute within the Translational Research Institute.

Dr Brooks completed his PhD at James Cook University researching Dengue Virus. He undertook a Postdoctoral Fellowship at St Jude Children's Research Hospital in Memphis, USA where he researched the role of Epstein-Barr Virus in B-cell lymphomagenesis. Following this, he joined the Institute for Molecular Bioscience at The University of Queensland.

His research has led to publications in journals including Science, Hepatology, Nature Cell Biology, Blood, PNAS, and Oncogene. He has been the recipient of more than $4.3 million in research grant funding and has several national and international collaborations. He is an Editorial Board member for the Journal Cancers and Review Editor for Molecular and Structural Endocrinology for the Journal Frontiers in Endocrinology. He has been a committee member of Australian Early-Mid Career Researchers Forum (AEMCRF) launched by the Australian Academy of Science.

Recent journal publications on this body of research

Ishikawa M., Brooks A.J., Fernández‐Rojo M.A., et al, "Growth hormone stops excessive inflammation after partial hepatectomy allowing liver regeneration and survival via induction of H2‐Bl/HLA‐G", Hepatology, 27 April 2020. https://doi.org/10.1002/hep.31297

Bridgford J.L., Lee S.M., Lee C., et al, “Novel drivers and modifiers of MPL-dependent oncogenic transformation identified by deep mutational scanning”, Blood, 2020; 135 4: 287-292.doi:10.1182/blood.2019002561

Chhabra Y., Nelson C.N., Plescher M., et al, “Loss of growth hormone-mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity”, FASEB, 2019; fj201802328R. doi:10.1096/fj.201802328R

Campos L.W, Zenatti P.P., Pissinato L.G., et al, “Oncogenic basic amino acid insertions at the extracellular juxtamembrane region of IL7Rα cause receptor hypersensitivity”, Blood, 2019;133 11: . doi:10.1182/blood-2018-09-872945

Dehkhoda F., Lee C.M.M., Medina J., Brooks A.J., “The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects”, Frontiers in Endocrinology, 2018;9 35: 35. doi:10.3389/fendo.2018.00035

Chhabra Y., Wong H.Y., Nikolajsen, L.F., et al, “A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation”, Oncogene, 2018; 37 4: 489-501. doi:10.1038/onc.2017.352