Metabolic Research Unit

The research goal of the Metabolic Research Unit is to understand how metabolism is regulated and what role hormones play for maintaining normal fat and muscle mass. Special focus is on establishing hormonal interactions in the regulation of metabolism, and the use of resistance training and diabetes drugs to suppress cancer progression. Located at the Blacktown Clinical School and Research Centre, Blacktown Hospital, the Metabolic Research Unit is equipped to perform a wide range of body composition, energy expenditure, substrate utilization, physical capacity, muscle strength, and balance assessments. State-of-the-art techniques are implemented using stable isotopes to investigate whole body protein metabolism, urea turnover, and liver VLDL production. This laboratory is the only one in Australia who can perform such complex stable isotope studies in humans. The focus is to establish a network of collaborative projects in WSLHD in endocrine, metabolic and cancer research, investigating hormonal control of metabolism and cancer development, integrating endocrinology and oncology at WSLHD.

Specific ongoing projects:

“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, (Opens in a new window) Amy Hayden, Anne Poljak, Birinder Cheema, Howard Gurney, Glenn Stone, Navneeta Reddy, (opens in a new window) Haleh Shahidipour, (opens in a new window) Vita Birzniece. (opens in a new window)

“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, (opens in a new window) Amy Hayden, Howard Gurney, Navneeta Reddy, (opens in a new window) Jan Frystyk, Vita Birzniece. (opens in a new window)

“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, (opens in a new window) Mark McLean, (opens in a new window) Haleh Shahidipour, (opens in a new window) Vita Birzniece. (opens in a new window)

“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, (opens in a new window) Vita Birzniece. (opens in a new window)

“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, (opens in a new window) Vita Birzniece, (opens in a new window) Mark McLean, (opens in a new window) Michael Edye, (opens in a new window) Ramy Bishay, (opens in a new window) Michael Devadas, Kathryn Williams, (opens in a new window) Jonathan Marks, Scott Read, (opens in a new window) Glen Maberly, (opens in a new window) Phillip Newton, (opens in a new window) Vicki Flood, (opens in a new window) Sarah Messer, (opens in a new window) Timothy Tan. (opens in a new window)

“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, (opens in a new window) Mark McLean, (opens in a new window) Neha Bahl, Vita Birzniece. (opens in a new window)


Current collaborators:

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).