Trimming the Fat: Targeting novel genetic factors and molecules that drive obesity

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1. SUMMARY

Obesity is a growing global pandemic, and a major risk factor for a number of life-threatening diseases such as diabetes, cardiovascular disease and cancer. Obesity is characterised by a persistent low-grade inflammation in fat tissue and disrupted metabolism. For the first time, my research has provided evidence of a genetic link between fat tissue inflammation and obesity in some people. RIPK1 is a central gene with critical roles in inflammation and cell death. I have identified novel genetic variants within this gene that correlate with increased risk of obesity in humans. Importantly, I showed that therapeutic silencing of RIPK1 in mice using small novel inhibitory RNA molecules reduces obesity and diabetes. The research team I lead is currently identifying novel target candidates for diagnostic applications and therapies to treat obesity, whilst promoting Queensland’s profile and expertise in obesity and other cardiometabolic disease research.

2. BENEFIT

Obesity rates are soaring at alarming rates world-wide, with at least ~66% of Queenslanders being overweight or obese. Rural Queensland is particularly affected, where 83% of people in Mackay and 75% in both Clermont and Richmond are overweight or obese. Obesity on its own is not life-threatening, however, it is arguably the greatest risk factor for many fatal diseases such as cardiovascular diseases, cancer and diabetes. Despite decades of large-scale public health interventions, such as diet and lifestyle changes, exercise regimes and drugs that curb appetite, the rates of obesity have continued to grow dramatically in Australia and world-wide. Troublingly, however there’s a huge misconception in the public that ‘you are what you eat’, and ‘if you exercise, you’ll lose weight’. But, as some of us know from personal experience, and now my and others' research show, there’s much more to the obesity equation. Diet and lifestyle factors are very important, but they are not the sole cause of obesity. 

My research has identified in a small subset of people, for the first time, genes and genetic factors that directly regulate fat tissue inflammation, which in turn drives obesity. This discovery shows that genetic factors directly control fat tissue inflammation and, importantly, it is only ‘the tip of the iceberg’. This research is paving the way towards diagnosing people carrying genetic factors that give them an increased risk of becoming obese. This may enable preventive measures and/or treatment of fat tissue inflammation and obesity in these people. The team that I lead is now focusing on finding more genetic factors and molecules that regulate fat tissue inflammation that drive obesity and cardiovascular diseases. It’s likely that specific genetic factors affect subsets of the population and having this knowledge will empower us to devise diagnosis and therapies.

Despite the growing obesity problem, research on these complex molecular mechanisms that drive obesity is limited in most Australian states, and in particular in Queensland. Given the high rates of obesity and associated co-morbidities in this state, especially in some rural populations, it is vital to invest time and resources to map the specific inflammatory pathways that drive obesity. By using novel, cutting-edge technologies to identify specific genetic factors and molecules that regulate inflammation, my research provides insights and molecular snapshots of disease mechanisms. By sourcing blood and tissue samples from lean and obese Queenslanders, I will increase our chances of identifying other factors that can be directly translated to specific subsets of the Queensland population in long-term.

Queensland is home to distinguished research-based universities, institutes and hospitals, and is an emerging health and medical research hub within Australia, especially in the areas of immunology and cancer therapies. One of my long-term goals and challenges is to place Queensland on the ‘map of obesity and cardiovascular research’, both in Australia and worldwide. I envision that my research team led by me will identify several novel inflammatory genetic factors that drive obesity in the coming years, which can then be targeted for diagnostic applications or therapies.

3. ENGAGEMENT

I am an ardent advocate for medical research and for women in science. I am passionate about sharing my research through various platforms (social media, public outreach, scientific communities). Explaining medical research discoveries across ‘all walks of life’ is very exciting and rewarding. Early in my career, I focused predominantly on community outreach (e.g. ‘Scientists in School Program’, ‘Gene Research for a Week’ program, Australian Society for Medical Research Medical Research Week).

More recently, I have strived to contribute in many ways through a ‘lead by example’ approach, where I can be an inspiration and motivation for other young female scientists, especially to those with a similar background to myself. I lifted my profile within the scientific community by showcasing my research findings at national and international conferences, securing numerous travel and other awards that recognise my scientific contribution and leadership (e.g. American Heart Association ATVB Early Career Investigator Award finalist, American Society for Investigative Pathology Young Scientist Leadership Award). Strategically increasing my professional profile presented the opportunity to champion other female researchers, highlight the importance of female inclusion to my peers and provide a leadership example to follow. While this approach has made me ‘well-known’ in my field of research and provided interaction with leaders in the field, most importantly it has also allowed me to advocate young female scientists. In turn, I’ve been invited to be an American Society for Investigative Pathology Ambassador to promote young women and research in pathology and an Ambassador for Australian Society for Immunology twitter campaign for ‘Women and Girls in Science’. I found it an incredible honour to represent fellow Australian women through these societies, as it provides excellent recognition for women in STEM in Queensland.

Another important facet of my contributions to young scientists is mentoring. I’m now in a position to mentor and support young female researchers to actively pursue their dreams in STEM. I take great pride and satisfaction in providing networking opportunities and mentoring for other young scientists. As a result of my advocacy for mentorship, I have been invited to participant in various career panels at national (e.g. Australian Atherosclerosis Society Meeting) and international conferences (e.g. American Heart Association Scientific Sessions). I also instigated a Young Scientist Career Symposium sponsored by Canadian Institutes for Health Research at the International Atherosclerosis Society Meeting in 2018 and was invited back as a Chair of the organising committee in 2019. Now, on UN International Day of Women and Girls in Science (Feb 11th 2020), I’m officially launching my twitter platform ‘#positive_mentor’ as a way to share my experiences and mentorship advice with women in STEM.

Lastly, as an IMB Fellow at UQ, I contribute my time and research discoveries in support of the Institute’s strategic engagement efforts in 2020 to highlight critical health issues experienced in Australia and the economic impact of ageing and inflammation. I am also supporting the Institute’s Women in STEM campaign and engagement to help address the gender imbalance apparent in mid- and senior-career level researchers. 

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I'm a Team Leader/IMB Fellow at the Institute for Molecular Bioscience, The University of Queensland. My research interests are in inflammation, immune cells (e.g. macrophages), obesity and atheros...

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