Metabolic Research Unit

1. “Novel mechanisms of metabolic derangements during testosterone withdrawal and role of exercise in preventing adverse health outcomes in prostate cancer” (ACTRN12616001311448). The purpose of this multicentre clinical trial is to prevent androgen deprivation-induced side effects in prostate cancer patients by progressive resistance training introduced at the start of androgen deprivation therapy. This project will provide knowledge on the extent, causes and timing of adverse metabolic effects of androgen deprivation, enabling earlier monitoring and prevention of metabolic complications in prostate cancer patients. The aim is also to discover the impact of bone- and muscle-derived factors in regulating metabolism that may affect prostate cancer outcomes.
   Investigators: Teresa Lam, Mark McLean, Amy Hayden, Anne Poljak, Birinder Cheema, Howard Gurney, Glenn Stone, Navneeta Reddy, Haleh Shahidipour, Vita Birzniece.
2. “Investigating the effects of metformin on growth factors involved in prostate cancer progression in prostate cancer patients” (ACTRN12615000778583). The purpose of this study is to determine the effect of metformin on certain growth factors that drive progression of prostate cancer. Metformin is a commonly used medication for the treatment of type 2 diabetes. We have early evidence that the use of metformin may slow down the growth of prostate cancer cells. However, the exact mechanism remains unknown. In this study participants will be randomly allocated to start with either metformin or placebo treatment in order to assess how metformin affects levels and activity of growth factors involved in prostate cancer progression. Metformin therefore may prove to be beneficial: 1) to prevent diabetes development in prostate cancer patients who receive androgen deprivation, and 2) to inhibit prostate cancer growth and spread.
   Investigators: Teresa Lam, Mark McLean, Amy Hayden, Howard Gurney, Navneeta Reddy, Jan Frystyk, Vita Birzniece.
3. “Muscle hormone (decorin) secretion in healthy people, and in patients with growth hormone (GH) deficiency and GH excess during exercise.” This clinical trial aims to determine the relationship between GH and decorin secretion in patients with GHD and acromegaly and healthy controls during acute exercise. We previously published that GH administration increases circulating decorin. Now we will establish whether GH and decorin are released simultaneously before, during and post exercise and how GH regulates decorin secretion. As decorin regulates connective tissue formation and skeletal muscle accretion, the expected reduction in decorin in patients with GHD will associate with reduced muscle mass and strength.
   Investigators: Navneeta Reddy, Mark McLean, Haleh Shahidipour, Vita Birzniece.
4. “Could changes in lipid species predict gestational diabetes and big babies?” The project aims to investigate: 1) the difference in lipid species between gestational diabetes and healthy pregnancie and 2) whether certain lipid species in mother can predict macrosomia. This analysis involves assessment of 305 circulating lipid species by lipidomics and subsequent sophisticated statistical data modelling to design a prediction profile. We anticipate that changes in certain circulating lipids could be used as a marker for diabetes development in pregnancy and to predict the growth of the baby.
   Investigators: Melinda Lam, Melina Bagala, Constance Yap, Peter Meikle, Natalie Mellett, Glenn Stone, Wah Cheung, Sue Lynn Lau, Mark McLean, Vita Birzniece.
5. “Relationship between Metabolic disease, Inflammation, Microbiome & Obesity (MIMO).” New program of lifestyle and surgical therapy for management of obesity and obesity-related diseases at Blacktown Hospital, WSU has been established. The overall aim of this research program is to investigate what factors determine weight gain and how diet or gastric surgery improve metabolism, and physical and mental health.
   Investigators: Golo Ahlenstiel, Vita Birzniece, Mark McLean, Michael Edye, Ramy Bishay, Michael Devadas, Kathryn Williams, Jonathan Marks, Scott Read, Glen Maberly, Phillip Newton, Vicki Flood, Sarah Messer, Timothy Tan.
6. “Mechanisms and novel markers of the anti-neoplastic effect of metformin in prostate cancer.” In this vitro project we aim to establish whether: 1) metformin inhibits prostate cancer growth and invasion through reducing IGF bioavailability and modification of IGFBPs; 2) metformin modifies protein and gene expression, DNA methylation and secretion of IGFs and IGFBPs in prostate cancer cells; 3) metformin affects cancer biology through modulating miRNAs directly, or through affecting IGFBPs that modulate miRNAs, thereby inhibiting prostate cancer cell growth, proliferation and invasion.
   Investigators: Haleh Shahidipour, Mark McLean, Neha Bahl, Vita Birzniece.

    

Prof Margot Umpleby and Dr Martin Whyte (University of Surrey, UK); Prof Hugh Barrett (UWA, WA); Dr Anne Poljak (UNSW Sydney); Prof Richard Lindley (Blacktown Hospital); Dr Wah Cheung, Prof Howard Gurney, Dr Amy Hayden and Dr Bo Gao (Westmead and Blacktown Hospitals, NSW); Dr Ruth Pidsley (Garvan Institute of Medical Research, NSW); Prof Glenn Stone and Dr Birinder Cheema (WSU, NSW); Prof Ken Ho (University of Queensland, Qld); Prof Robert Baxter (University of Sydney); Prof Jan Frystyk (Aarhus University, Denmark); Prof Stephen Lord (NeuRa, UNSW Sydney); Prof David Handelsman (ANZAC Research Institute); Dr Greg Smith (UNSW Sydney); Prof Bu Yeap (UWA, WA); Ms Natalie Mellett and Prof Peter Meikle (Baker Heart & Diabetes Institute, VIC).