Research

Research at the Ramaciotti Centre

Dr Ruby Lin is a research fellow based at the Ramaciotti Centre. Ruby has successfully used functional genomics to investigate molecular mechanisms of metabolism and its related disorders using microarrays and related technologies in human and rodent models. In molecular genetic studies she discovered a glucocorticoid receptor variant that confers increased risk of obesity and coronary artery disease in Anglo-Celtic Australian subjects and demonstrated the role of variation in this and other genes in essential hypertension, type 2 diabetes and coronary artery disease. She developed the first quantitative real-time RT-PCR method for TNF receptor 1 and 2 in rat models of hypertension while qRT-PCR was in its infancy in Australia. She then discovered an association of leptin with insulin resistance in non-diabetic adolescents. Her interest and focus on functional genomics resulted in developing the first diagnostic approach for sepsis by use of gene expression profiling in a clinical setting. This was a major breakthrough in the field of critical care medicine in terms of development of diagnostic strategy. It moreover addressed fundamental biology at a molecular level, capitalizing on the advent of high-throughput technologies. She has applied systems biology approach to address metabolism-related disorders in rodent and human cell culture models as well as mouse models of cardiovascular diseases. Together with her collaborators, she has identified microRNAs that can be used as possible therapeutics in myocardial infarction and is an inventor on a current US patent. Since 2003 she has been an invited reviewer for specialist journals such as Diabetes, Obesity and Metabolism, Clinical Biochemistry, Genetics in Medicine, Physiological Genomics and Biotechniques.

Active research projects

  1. Cardiac hypertrophy (Baker IDI Inst, Dr J McMullen) 2005- We are investigating the protective role of PI3K in PI3K transgene mouse models of myocardial infarction as well as atrial fibrillation. My expertise is experimental design and transcriptomics in mRNA and microRNA experiments and data analysis. 7 conference presentations. 1 successful NHMRC project grant (2010-12). 1 US patent. Publications in ATVB, JBC and Am J Pathology.
  2. Visualisation of mRNA and microRNA interactions using a systems biology approach (UNSW, Prof Marc Wilkins, Dr David Fung; Griffith Uni, Mr Ashley Waardenberg; Baker IDI, Dr J McMullen) 2009- Using mouse cardiac transcriptomics data, we are establishing visualisation of regulatory networks as well as modelling cardiac insult using a 3D Virtual Muscle model. Publication in JBC.
  3. Paternal effect on the offspring of Sprague Dawley rats fed on high fat diet (UNSW, Prof Margaret Morris, Dr SF Ng) 2009- Interdisciplinary research on the generational effect of high fat diet on islet and fat metabolism. Publication in Nature. 2 Conference presentations. 1 pending patent.

Publications (selected)

Waardenberg AJ, Bernardo BC, Ng DCH, Shepherd PR, Cemerlang N, Sbroggio M, Wells CA, Dalrymple BP, Brancaccio M, Lin RCY*, McMullen JR*. Phosphoinositide 3-kinase (p110α) directly regulates key components of the Z-disc and cardiac structure. Journal of Biological Chemistry 2011 jbc.M111.271684. First Published on July 11 2011. *Equal senior author

Fei W, Shui G, Zhang Y, Krahmer N, Ferguson C, Kapterian TS, Lin RCY, Dawes IW, Brown AJ, Li P, Huang X, Parton RG, Wenk MR, Walther TC and Yang H. A role for phosphatidic acid in the formation of "supersized" lipid droplets. PLoS Genetics on June 20th, 2011. DOI: 10.1371/journal.pgen.100220

Chung HC, Lin RCY, Logan GJ, Alexander IE, Sachdev P, Sidhu KS. Human induced pluripotent stem cells derived under feeder-free conditions display unique cell cycle and DNA replication gene profiles. Stem Cells & Development 2011, April 20th [Epub ahead of print]

Chiu J, Tactacan CM, Tan S, Lin RCY, Wouters MA, Dawes IW. Cell cycle sensing of oxidative stress in Saccharomyces cerevisiae by oxidation of a specific cysteine residue in the transcriptional factor Swi6p. Journal of Biological Chemistry 2011 286:5204-14. Epub 2010 Dec 8.

Ng SF, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature. 2010 467;963-6

Lin RCY, Weeks KL, Gao X-M, Williams RBH, Bernardo BC, Kiriazis H, Matthews VB, Woodcock EA, Bouwman R, Molica JP, Speirs HJ, Dawes IW, Daly RJ, Shioi T, Izomo S, Febbraio MA, Du S-J, McMullen JR. PI3K(p110) protects against myocardial infarction-induced heart failure: Identification of PI3K-regulated miRNAs and mRNAs. Arterioscelerosis, Thrombosis, and Vascular Biology. 2010 30:724-32

Pretorius L, Du X-J, Woodcock EA, Kiriazis H, Lin RCY, Marasco S, Medcalf RL, Ming Z, Head GA, Tan JW, Cemerlang N, Sadoshima J, Shioi T, Izumo S, Lukoshkova E, Dart AM, Jennings GL, McMullen JR. Reduced phosphoinositide 3-kinase(p110a) activation increases the susceptibility to atrial fibrillation. The American Journal of Pathology. 2009 175:998-1008

Tang BMP, McLean AS, Dawes IW, Huang SJ, Lin RCY. Gene-expression profiling of peripheral blood mononuclear cells in sepsis. Critical Care Medicine. 2009 37:882-8 Editorial: Crit Care Med. 2009 37(3):1137-1138

Tang BMP, McLean AS, Dawes IW, Huang SJ, Cowley M, Lin RCY. The gene-expression profiling of Gram-positive and Gram-negative sepsis in critically ill patients. Crit Care Med, 2008 36:1125-1128 *senior author. Editorial: Crit Care Med. 2008 Apr;36(4):1369-70.

Tang BMP, McLean AS, Dawes IW, Huang SJ, Lin RCY. The use of gene-expression profiling improves diagnosis of sepsis. American Journal of Respiratory and Critical Care Medicine 2007;176:676-684. *senior author. Editorial: Moldawer LL. Opening the window on genome-wide expression analyses in sepsis. Am J Respir Crit Care Med 2007:176:631-635.

Lin RCY, Wang WYS, Morris BJ. Association and linkage analyses of glucocorticoid receptor gene markers in essential hypertension. Hypertension 1999;34:1186-1192

Lin RCY, Wang WYS, Morris BJ. High penetrance, overweight, and glucocorticoid receptor variant: case-control study. British Medical Journal 1999;319:1337-1338

Professional Experience

Professional Activities

Invited Chair and Talks