Metabolomics Group

• 
  Head of Laboratory
  Professor Peter Meikle

  peter.meikle@baker.edu.au

  +61 3 8532 1770

Research Overview

Dysregulation of lipid metabolism underpins multiple diseases including obesity, type 2 diabetes, cardiovascular disease and age related dementia. While lipid metabolic pathways are well characterised, their dysregulation resulting from environmental and genetic influences are less well understood, particularly in a setting of chronic disease. The Metabolomics laboratory has utilised state-of-the-art tandem mass spectrometry to developed the only high-throughput lipidomic platform in Australia and has performed some of the largest clinical and population lipidomic studies yet reported. These have enabled the characterisation of metabolic pathways and identified lipidomic biomarker profiles that are able to better predict disease risk and therapeutic efficacy. Modulation of the same pathways now holds potential as an interventional strategy to prevent, attenuate or treat the major chronic diseases.

The overarching goal of the Metabolomics laboratory is to develop strategies to elucidate and combat the metabolic underpinnings of cardiometabolic disease.

We are applying our state of the art lipidomic capabilities to characterise the relationship between lipid metabolism and cardiometabolic disease. Clinical translation of the outcomes from these studies will deliver new diagnostic/risk assessment/monitoring tests and therapeutic interventions for chronic disease.

Staff

Dr Satvika Burugupalli
Dr Corey Giles
Dr Kevin Huynh
Dr Sudip Paul
Dr Alex Smith
Dr Tingting Wang
Ms Michelle Cinel
Ms Thy Duong
Ms Natalie Mellet
Ms Anh Nguyen

Collaborators

Zora Biosciences Oy / Mayo Clinic
Texas, Biomedical Research Institute, USA
Duke University
National University of Singapore
Umea University

Funding

NHMRC
NIH
Cancer Council Australia
LEW Carty Charitable Fund

Research Outcomes

Publications 2015-20

1. Ursino GM, Fu Y, Cottle DL, Mukhamedova N, Jones LK, Low H, et al. ABCA12 regulates insulin secretion from beta-cells. EMBO Rep. 2020;21(3):e48692.
2. Triebl A, Burla B, Selvalatchmanan J, Oh J, Tan SH, Chan MY, et al. Shared reference materials harmonize lipidomics across MS-based detection platforms and laboratories. Journal of lipid research. 2020;61(1):105–15.
3. Tan SM, Ziemann M, Thallas-Bonke V, Snelson M, Kumar V, Laskowski A, et al. Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility. Diabetes. 2020;69(1):83–98.
4. Mukhamedova N, Huynh K, Low H, Meikle P, and Sviridov D. Isolation of Lipid Rafts from Cultured Mammalian Cells and Their Lipidomics Analysis. Bio-Protocol. 2020;10(13).
5. Low H, Mukhamedova N, Capettini L, Xia Y, Carmichael I, Cody SH, et al. Cholesterol Efflux-Independent Modification of Lipid Rafts by AIBP (Apolipoprotein A-I Binding Protein). Arteriosclerosis, thrombosis, and vascular biology. 2020:ATVBAHA120315037.
6. Lim WLF, Huynh K, Chatterjee P, Martins I, Jayawardana KS, Giles C, et al. Relationships Between Plasma Lipids Species, Gender, Risk Factors, and Alzheimer's Disease. J Alzheimers Dis. 2020;76(1):303–15.
7. Krycer JR, Quek LE, Francis D, Zadoorian A, Weiss FC, Cooke KC, et al. Insulin signalling requires glucose to promote lipid anabolism in adipocytes. The Journal of biological chemistry. 2020.
8. Hilvo M, Meikle PJ, Pedersen ER, Tell GS, Dhar I, Brenner H, et al. Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. Eur Heart J. 2020;41(3):371–80.
9. Genders AJ, Connor T, Morrison S, Bond ST, Drew BG, Meikle PJ, et al. Reducing hepatic PKD activity lowers circulating VLDL cholesterol. J Endocrinol. 2020;246(3):265–76.
10. Ekholm J, Ohukainen P, Kangas AJ, Kettunen J, Wang Q, Karsikas M, et al. EpiMetal: an open-source graphical web browser tool for easy statistical analyses in epidemiology and metabolomics. Int J Epidemiol. 2020.
11. Chu KY, Mellet N, Thai LM, Meikle PJ, and Biden TJ. Short-term inhibition of autophagy benefits pancreatic beta-cells by augmenting ether lipids and peroxisomal function, and by countering depletion of n-3 polyunsaturated fatty acids after fat-feeding. Mol Metab. 2020;40:101023.
12. Chu AHY, Tint MT, Chang HF, Wong G, Yuan WL, Tull D, et al. High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort. International journal of obesity. 2020.
13. Chapman MJ, Orsoni A, Tan R, Mellett NA, Nguyen A, Robillard P, et al. LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL. Journal of lipid research. 2020;61(6):911–32.
14. Cadby G, Melton PE, McCarthy NS, Giles C, Mellett NA, Huynh K, et al. Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study. Journal of lipid research. 2020;61(4):537–45.
15. Beyene HB, Hamley S, Giles C, Huynh K, Smith A, Cinel M, et al. Mapping the Associations of the Plasma Lipidome With Insulin Resistance and Response to an Oral Glucose Tolerance Test. J Clin Endocrinol Metab. 2020;105(3).
16. Arnold M, Nho K, Kueider-Paisley A, Massaro T, Huynh K, Brauner B, et al. Sex and APOE epsilon4 genotype modify the Alzheimer's disease serum metabolome. Nature communications. 2020;11(1):1148.
17. Amorim NML, Kee A, Coster ACF, Lucas C, Bould S, Daniel S, et al. Irradiation impairs mitochondrial function and skeletal muscle oxidative capacity: significance for metabolic complications in cancer survivors. Metabolism: clinical and experimental. 2020;103:154025.
18. Wallert M, Ziegler M, Wang X, Maluenda A, Xu X, Yap ML, et al. alpha-Tocopherol preserves cardiac function by reducing oxidative stress and inflammation in ischemia/reperfusion injury. Redox Biol. 2019;26:101292.
19. Sung HH, Sinclair AJ, Huynh K, Smith AT, Mellett NA, Meikle PJ, et al. Differential plasma postprandial lipidomic responses to krill oil and fish oil supplementations in women: A randomized crossover study. Nutrition. 2019;65:191–201.
20. Selvadurai MV, Brazilek RJ, Moon MJ, Rinckel JY, Eckly A, Gachet C, et al. The PI 3-kinase PI3KC2alpha regulates mouse platelet membrane structure and function independently of membrane lipid composition. FEBS letters. 2019;593(1):88–96.
21. Sari CI, Eikelis N, Head GA, Schlaich M, Meikle P, Lambert G, et al. Android Fat Deposition and Its Association With Cardiovascular Risk Factors in Overweight Young Males. Frontiers in physiology. 2019;10:1162.
22. Pradas I, Jove M, Huynh K, Puig J, Ingles M, Borras C, et al. Exceptional human longevity is associated with a specific plasma phenotype of ether lipids. Redox Biol. 2019;21:101127.
23. Paul S, Lancaster GI, and Meikle PJ. Plasmalogens: A potential therapeutic target for neurodegenerative and cardiometabolic disease. Prog Lipid Res. 2019;74:186–95.
24. Parker BL, Calkin AC, Seldin MM, Keating MF, Tarling EJ, Yang P, et al. An integrative systems genetic analysis of mammalian lipid metabolism. Nature. 2019;567(7747):187–93.
25. Mukhamedova N, Hoang A, Dragoljevic D, Dubrovsky L, Pushkarsky T, Low H, et al. Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells. PLoS Pathog. 2019;15(7):e1007907.
26. Mousa A, Naderpoor N, Mellett N, Wilson K, Plebanski M, Meikle PJ, et al. Lipidomic profiling reveals early-stage metabolic dysfunction in overweight or obese humans. Biochem Biophys Acta Mol Cell Biol Lipids. 2019;1864(3):335–43.
27. Meikle PJ, Formosa MF, Mellett NA, Jayawardana KS, Giles C, Bertovic DA, et al. HDL Phospholipids, but Not Cholesterol Distinguish Acute Coronary Syndrome From Stable Coronary Artery Disease. J Am Heart Assoc. 2019;8(11):e011792.
28. Loh K, Tam S, Murray-Segal L, Huynh K, Meikle PJ, Scott JW, et al. Inhibition of Adenosine Monophosphate-Activated Protein Kinase-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Signalling Leads to Hypercholesterolemia and Promotes Hepatic Steatosis and Insulin Resistance. Hepatol Commun. 2019;3(1):84–98.
29. Jayawardana KS, Mundra PA, Giles C, Barlow CK, Nestel PJ, Barnes EH, et al. Changes in plasma lipids predict pravastatin efficacy in secondary prevention. JCI Insight. 2019;4(13).
30. Huynh K, Barlow CK, Jayawardana KS, Weir JM, Mellett NA, Cinel M, et al. High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors. Cell Chem Biol. 2019;26(1):71–84 e4.
31. Haynes VR, Keenan SN, Bayliss J, Lloyd EM, Meikle PJ, Grounds MD, et al. Dysferlin deficiency alters lipid metabolism and remodels the skeletal muscle lipidome in mice. Journal of lipid research. 2019;60(8):1350–64.
32. Findeisen M, Allen TL, Henstridge DC, Kammoun H, Brandon AE, Baggio LL, et al. Treatment of type 2 diabetes with the designer cytokine IC7Fc. Nature. 2019;574(7776):63–8.
33. Diehl P, Nienaber F, Zaldivia MTK, Stamm J, Siegel PM, Mellett NA, et al. Lysophosphatidylcholine is a Major Component of Platelet Microvesicles Promoting Platelet Activation and Reporting Atherosclerotic Plaque Instability. Thromb Haemost. 2019;119(8):1295–310.
34. Chu KY, O'Reilly L, Mellet N, Meikle PJ, Bartley C, and Biden TJ. Oleate disrupts cAMP signalling, contributing to potent stimulation of pancreatic beta-cell autophagy. The Journal of biological chemistry. 2019;294(4):1218–29.
35. Cantley J, Davenport A, Vetterli L, Nemes NJ, Whitworth PT, Boslem E, et al. Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass. Diabetologia. 2019;62(1):99–111.
36. Brandon AE, Liao BM, Diakanastasis B, Parker BL, Raddatz K, McManus SA, et al. Protein Kinase C Epsilon Deletion in Adipose Tissue, but Not in Liver, Improves Glucose Tolerance. Cell Metab. 2019;29(1):183–91 e7.

Research Publications

1. Hilvo M, Meikle PJ, Pedersen ER, Tell GS, Dhar I, Brenner H, et al. Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. Eur Heart J. 2020;41(3):371–80.
2. Cadby G, Melton PE, McCarthy NS, Giles C, Mellett NA, Huynh K, et al. Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study. Journal of lipid research. 2020;61(4):537–45.
3. Beyene HB, Hamley S, Giles C, Huynh K, Smith A, Cinel M, et al. Mapping the Associations of the Plasma Lipidome With Insulin Resistance and Response to an Oral Glucose Tolerance Test. J Clin Endocrinol Metab. 2020;105(3).
4. Paul S, Lancaster GI, and Meikle PJ. Plasmalogens: A potential therapeutic target for neurodegenerative and cardiometabolic disease. Prog Lipid Res. 2019;74:186–95.
5. Parker BL, Calkin AC, Seldin MM, Keating MF, Tarling EJ, Yang P, et al. An integrative systems genetic analysis of mammalian lipid metabolism. Nature. 2019;567(7747):187–93.
6. Jayawardana KS, Mundra PA, Giles C, Barlow CK, Nestel PJ, Barnes EH, et al. Changes in plasma lipids predict pravastatin efficacy in secondary prevention. JCI Insight. 2019;4(13).
7. Huynh K, Barlow CK, Jayawardana KS, Weir JM, Mellett NA, Cinel M, et al. High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors. Cell Chem Biol. 2019;26(1):71–84 e4.
8. Findeisen M, Allen TL, Henstridge DC, Kammoun H, Brandon AE, Baggio LL, et al. Treatment of type 2 diabetes with the designer cytokine IC7Fc. Nature. 2019;574(7776):63–8.
9. Mundra PA, Barlow CK, Nestel PJ, Barnes EH, Kirby A, Thompson P, et al. Large-scale plasma lipidomic profiling identifies lipids that predict cardiovascular events in secondary prevention. JCI Insight. 2018;3(17).
10. Lin HM, Mahon KL, Weir JM, Mundra PA, Spielman C, Briscoe K, et al. A distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer. Int J Cancer. 2017;141(10):2112–20.
11. Alshehry ZH, Mundra PA, Barlow CK, Mellett NA, Wong G, McConville MJ, et al. Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus. Circulation. 2016;134(21):1637–50.