Lipid Research Group

About us

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and premature death worldwide. To a large extent, this is a consequence of the ageing population, as well as the increasing prevalence of type 1 and type 2 diabetes in younger generations. High plasma high density lipoprotein (HDL) cholesterol levels are associated with a reduced risk of ASCVD. This benefit may be related to the multiple cardioprotective functions HDLs. We have recently shown that HDLs also have anti-diabetic properties.

The overall goal of the Lipid Research Group is to understand the mechanisms that underlie the development of cardiovascular complications in diabetes and the identification of novel therapeutic approaches for treating these diseases.

Current Projects

  • Understanding the anti-diabetic properties of HDLs
  • Development of mimetic peptides as anti-atherosclerotic and anti-diabetic therapies
  • Identification of novel cardioprotective functions of HDLs
  • Regulation of ASCVD by miRNAs
  • Identification of novel biomarkers as predictors of cardiovascular risk
  • Characterising the impact of impaired cholesterol homeostasis on cellular function in endocrine and immune cells

Research Opportunities

There are opportunities for Honours, PhD and ILP students: contact Prof Kerry-Anne Rye for details of specific projects.

Team

Collaborators

  • Dr Gary Ren, Lawrence Berkeley Laboratory, CA, USA.

HDLstructure and function
Interactions of HDLs and cholesteryl ester transfer protein

  • Dr Alan RemaleyNHLBI, Bethesda, MD, USA

Regulation of HDL function by mimetic peptides

  • A/Prof Veronique Angeli, National University of Singapore

·             ApoA-I and lymphatic biology

  • Dr Kasey Vickers, Vanderbilt University, TN, USA

·             miRNAs in health and disease

  • Dr Roshni Singaraja, A*Star, Singapore

            Role of ABCA8 in cardiometabolic disease

Resources & Tools

Publications (2016-Present)

Cochran, B.J., Ryder, W.J., Parmar, A., Klaeser, K., Reilhac, A., Angelis, G., Meikle, S.R., Barter, P.J., Rye, K.-A.

Determining glucose metabolism kinetics using 18F-FDG micro-PET/CT

J Vis Exp. 2017 123: doi: 10.3791/55184

Van der Vorst, E.P.C., Theodorou, K., Wu, Y., Hoeksema, M.A., Goossens, P., Bursill, C.A., Aliyev, T., Huitema, L.F.A., Tas, S., W., Wolfs, I.M.J., Kuijpers,M.J.E., Gijbels, M.J., Schalkwijk, C.G., Koonen, D.P.Y., Abdollahi-Roodsaz, S., Leitges,M., Lawrence, T., Touqui, L., Plat, J., van Eck, M., Rye, K.-A., de Winher, M.P.J., Biessen, E.A.L., and Donners, M.M.P.C.

High Density Lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-κB/STAT1-IRF1 activation

Cell Metabolism. 2017 25:197-207

Charlton, F., Bobek, G., Stait-Gardner, T., Price, W., Colafella, K.M., Xu, B., Makris, A., Rye, K.-A., Hennessy, A.

The protective effect of apolipoprotein in models of trophoblast invasion and preeclampsia

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017 312:R40-R48

Kokkinos, J., Tang, S., Rye, K.-A. and Ong, K.L.

The role of fibroblast growth factor 21 in atherosclerosis

Atherosclerosis 2017 257:259-265

Pandzic, E., Gelissen, I., Whan, R., Barter, P.J., Sviridov, D., Gaus, K., Rye, K.-A., Cochran, B.J.

The ATP binding cassette transporter, ABCG1, localizes to cortical actin filaments.

Scientific Reports. 2017 7:42025

Ong, K.L., O’Connell, R., Januszewski, A., Jenkins, A.J., Xu, A., Sullivan, D.R., Barter, P.J., Scott, R.S., Taskinen, M.-R., Waldman, B., Colman, P.G., Best, J.D., Simes, J.R., Rye, K.-A.*, Keech, A.C.*      *Equal contribution

Baseline circulating FGF21 levels and increase after fenofibrate treatment predict more rapid glycemic progression in type 2 diabetes: Results from the FIELD Study

Clinical Chemistry. 2017 63:1261-1270

Barter, P.J. and Rye, K.-A.

HDL cholesterol concentration or HDL function: Which matters?

Eur. Heart Journal 2017 38:2487-2489

Rosenson, R., Brewer, H.B., Barter, P., Bjorkgren, J., Chapman, M., Gaudet, D., Kim, D., Neisor, E., Rye, K.-A., Sacks, F.M., Tardif, J.-C., and Hegele, R.

High density lipoproteins and atherosclerotic cardiovascular disease: Genetic insights on complex biology.

Nature Reviews Cardiol. 2017 15:9-19

Da Silva, K.S., Pinto, P.R., Fabre, N.T., Gomes, D.J., Thieme, K., Okuda, L.S., Iborro, R.T., Freitas, V.G., Shimizu, M.H.M., Teodoro, W.R., Marie, S.K.N., Woods, T., Brimble, M.A., Pickford, M.A., Rye, K.-A., Okamoto, M., Catanozi. S., Machado, U.F., Correa-Giannela, M.L., Passarelli, M.

N-acetyl cysteine counteracts adipose tissue macrophage infiltration and insulin resistance elicited by advanced glycated albumin in healthy rats

Frontiers in Physiology. 2017 8:723 (doi: 10.3389/fphys.2017.00723)

Zhang, M., Lei, D., Peng, B., Yang, M., Zhang, L., Charles, M.A., Rye, K.-A., Krauss, R.M., Johns, D.G., Ren, G.

Assessing the mechanisms of cholesteryl ester transfer protein inhibitors.

Biochim. Biophys. Acta 2017 1862:1606-1617

Iborra, R.T., Machado-Lima, A., Okuda, L.S., Pinto, R., Nakandakare, E.R., Machado, U.F., Correa-Giannella, M.L., Pickford, R., Woods, T., Brimble, M.A., Rye, K.-A., Lu, R., Yokoyama, S., Passarelli, M.

AGE-albumin enhances ABCA1 degradation by ubiquitin-proteasome and lysosomal pathways in macrophages.

J. Diabetes Complications. 2018 30:1-10

Melchior, J.T., Walker, R.G., Cooke, A.L., Morris, J., Castleberry, M., Thompson, T.B., Jones, M.K., Song, H.D., Rye, K.-A., Oda, M.N., Sorci-Thomas, M.G., Thomas, M.J., Heinecke, J.W., Mei, X., Atkinson, D., Segrest, J.P., Lund-Katz, S., Phillips, M.C., and Davidson, W.S.

A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state

Nature Struct and Molec Biol. 2017 24: 1093-1099

Wu, B.J., Li, Y., Ong, K.L., Sun, Y., Shrestha, S., Hou, L., Johns, D., Barter, P.J. Rye, K.-A.

Reduction of in-stent stenosis by cholesterol ester transfer protein inhibition.

Arterioscler. Thromb. Vasc. Biol. 2017 37:2333-2341

Chung, R., Wang, Z., Bursill, C.A., Wu, B., Barter, P.J. and Rye, K.-A.

Effect of long term dietary sphingomyelin supplementation on atherosclerosis in mice

PLoS One. 2017 12: e0189523. (doi: 10.1371/journal.pone.0189523)

Hui, T.H., McClelland, R.L., Allison, M.A., Rodriguez, C.J., Krommal, R.A., Heckbert, S.R., Michos, E.D., Barter, P.J., Rye, K.-A., Ong, K.L.

The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

Atherosclerosis 2017 269:86-91

Aleidi, S.M., Yang, A., Sharpe, L.J., Rao, G., Cochran, B.J., Rye, K.-A., Kockx, M., Brown, A.J. and Gellison, I.C.

The E3 ubiquitin ligase, HECTD1, is involved in ABCA1-mediated cholesterol export from macrophages

BBA – Molecular and Cell Biology of Lipids. 2018 1863: 359-368

Choteau, S.A., Cuesta Torres, L., Barraclough, J.Y., Elder, A,, Martinez, G.J., Chen Fan, W.Y., Shrestha, S., Ong, K.L., Barter, P.J., Celermajer, D.S., Rye, K.-A.*, Patel, S.*, Tabet, F*. *Equal contribution

Transcoronary gradients of HDL-associated microRNAs in unstable coronary artery disease

Int J. Cardiol. 2018 253:138-144

Persdegol, L., Darabi, M., Dauteuille, C., Lhomme, M., Chantepie, S., Rye, K.-A., Therond, P., Chapman, M.J., Salvayre, R., Negre-Salvayre, A., Lesnik, P., Monier, S., and Kontush, A.

Small, dense high density lipoproteins display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate

J Lipid Res 2018 59:25-34

Ong, K.L., Morris, M.J., McClelland, R.L., Hughes, T.M., Maniam, J., Fitzpatrick, A.L., Martin, S.S., Luchsinger, J.A., Rapp, S.R., Hayden, K.M., Sandfort, V., Allison, M.A. and Rye, K.-A.

Relationship of lipid and lipid-lowering medications with cognitive function: The Multi-Ethnic Study of Atherosclerosis.

Am J Epidemiol. 2018 187:787-776

Arsenault, B.J., Petrides, F., Tabet, F., Bao, W., Hovingh, G.K., Boekholdt, S.M., Meilhac, O., DeMicco, D., Rye, K.-A., Waters, D.D., Kastelein, J.J.P., Barter, P. and Lambert, G.

Effect of atorvastatin, CETP inhibition and diabetes mellitus on circulating PCSK9 and lipoprotein(a) levels in patients at high cardiovascular risk.

J Clin Lipidol. 2018 12:130-136

Ong, K.L., Waters, D.D., Fayyad, R., Vogt L., Melamed, S., DeMicco, D.A., Rye, K.-A., Barter, P.J.

Relationship of HDL cholesterol with renal function in patients treated with atorvastatin.

J Am Heart Assoc. 2018 Jan 22;7(2). pii: e007387. doi: 10.1161/JAHA.117.007387

Barter, P.J. and Rye, K.-A.

Cholesteryl ester transfer protein inhibitors as agents to reduce coronary heart disease risk.

Cardiol. Clin. 2018 36:299-310

Shrestha, S., Wu, B.J., Guiney, L., Barter, P.J., Rye, K.-A.

Cholesteryl ester transfer protein and its inhibitors.

J Lipid Res. 2018 59:772-783

Anuwatmatee, S., Allison, M.A., Shlipak, M.G., McClelland. R.L., Kramer, H., Tang, S., Hou, L., Rye, K.-A., Ong, K.L.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: Multi-Ethnic Study of Atherosclerosis

Nephrology Dialysis Transplantation. In press. Date of acceptance: April 9, 2018

Wewege, M., Thom, J., Rye, K.-A., Parmenter, B.

Aerobic, Resistance or Combined Training: A SystemaNc Review and Meta-Analysis of Exercise to Reduce Cardiovascular Risk in Adults with Metabolic Syndrome

Atherosclerosis. 2018 274:162-171

Robinson, J.G., Williams, K.J., Gidding, S., Boren, J., Tabas, I., Fisher, E.A., Packard, C., Pencina, M., Fayad, Z.A., Mani, V., Rye, K.-A., Nordestgaard, B.G., Tybaerg-Hansen, A., Douglas, P.A., Nicholls, S., Pagidipati, N., Sniderman, A.

Eradicating the burden of atherosclerotic cardiovascular disease by lowering apolipoprotein B lipoprotein earlier in life.

J Am Heart Assoc 2018 7:e009778. DOI: 10.1161/JAHA.118.009778

Jones, B., Buenaventura, T., Kanda, N., Chabosseau, P., Owen, B.M., Scott, R., Goldin, R., Angkathunyakul, N., Corrêa, I.R., Bosco, D., Johnson, P.R., Piemonti, L., Marchetti, P., Shapiro, A.M.J., Cochran, B.J., Hanyaloglu, A., Inoue, A., Tan, T., G.A., Tomas, A. and Bloom, S.R.
Functional and therapeutic consequences of GLP-1 receptor trafficking in type 2 diabetes.
Nature Communications 2018 9:1602.

Barter, P.J., Cochran, B.J. and Rye, K.-A.

CETP inhibition, statins and diabetes.

Atherosclerosis. 2018 278:143-146

Ong, K.L., McClelland, R.L., Allison, M.A., Kokkinos, J., Wu, B.J., Barter, P.J. and Rye, K.-A.

Association of elevated circulating fibroblast growth factor 21 levels with prevalent and incident metabolic syndrome: The Multi-Ethnic Study of Atherosclerosis

Atherosclerosis. 2019 281:200-206

Yuan, D., Wu, B.J., Henry, A., Rye, K.-A., and Ong, K.L.

Role of fibroblast growth factor 21 in gestational diabetes mellitus

Clinical Endocrinology. 2018 90:47-55

Kim, W., He, Y., Phan, K., Ahmed, R., Rye, K.-A., Piguet, O., Hodges, J., Halliday, G.

Altered high density lipoprotein composition in behavioural variant frontotemporal dementia

Frontiers in Neuroscience. 2018 12:847. doi.org/10.3389/fnins.2018.00847

Ong. K.L., Hui, N., Januszewski, A.S., Kaakoush, N.O., Xu, A., Fayyad, R., DeMicco, D.A., Jenkins, A.J., Keech, A.C., Waters, D.D., Barter, P.J., Rye, K.-A.

High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets (TNT) study.

Metabolism. 2019 93:93-99

Tang, S., Tabet, F., Cochran, B.J., Cuesta Torres, L., Wu, B.J., Barter, P.J., Rye, K.-A.

Apolipoprotein A-I enhances insulin-dependent and insulin-independent glucose uptake by skeletal muscle.

Scientific Reports. 9:1350

Anuwatmatee, S., Tang, S, Wu, B.J., Rye, K.-A., and Ong, K.L.

Fibroblast growth factor 21 in kidney disease.

Clinica Chinica Acta 2019 489:196-202

Cochran, B.J., Trajanovska, S., Sunn, N., Rye, K.A. and Ryder, W.J.
Development of 3D printing filaments for bespoke X-Ray phantoms.
IEEE Xplore 2019 In press. Date of Acceptance: Janurary 14, 2019

Hackett, M., Hollings, A., Majimbi, M., Brook, E., Cochran, B., Giles, C., Lam, V., Nesbit, M., Rye, K.-A., Mamo, J., Takechi, R.

The homeostasis of clopper, lipids and energy metabolism are altered in the hippocampal formation of non-insulin dependent diabetic mice.

ACS Chemical Neuroscience 2019 In press. Date of Acceptance: March 8, 2019

Kopecky, C., Pandzic, E., Parmar, A., Szajer, J., Lee, V., Dupuy, A., Artherur, A., Fok, S., Whan, R., Ryder, W.J., Rye, K.-A., and Cochran, B.J.

Translocator protein localises to CD11b+ macrophages in atherosclerosis

Atherosclerosis 2019 284:153-159

Tabet, F., Lee, S., Zhu, W., Levin, M.G., Toth, C.L., Cuesta Torres, L., Vinh, A., Kim, H.A., Chu, H.X., Evans, M.A., Kuzmich, M.E., Drummong, G.R., Remaley, A.T., Rye, K.-A., Sobey, C., Vickers, K.C.

MicroRNA-367-3p regulation of GPCRC5A is suppressed in ischemic stroke.

Journal of Cerebral Flow and Metabolism 2019 In press. Date of Acceptance: March 21, 2019

Kopecky, C., Lytvyn, Y., Domenig, O., Antlanger, M., Kovarik, J.J., Kaltenecker, C.C., Poglitsch, M., Perkins, B.A., Rye, K.-A., Cherney, D.Z.I., Saemann, M.D.

Molecular regulation of the renin-angiotensin system by sodium-glucose transporter 2 inhibition in type 1 diabetes mellitus.

Diabetologia 2019 In press. Date of Acceptance: March 21, 2019

Hou, L., Tang, S., Wu, BJ., Ong, K.L., Westerterp, M., Barter, P.J., Cochran, B.J., Tabet, F. and Rye, K.-A.

Apolipoprotein A-I improves pancreatic beta cell function independent of the ATP binding cholesterol transporters ABCA1 and ABCG1

FASEB J. 2019. In press. Date of Acceptance: March 27, 2019

Wu, B.J., Sun, Y.. Ong, K.-L., Tang, S., Barter, P.J. and Rye, K.-A.

Apolipoprotein A-I protects against pregnancy-induced insulin resistance in rats.

Arterioscler. Thromb. Vasc. Biol. In press. Date of Acceptance: April 16, 2019

Cuesta Torres, L.F., Zhu, W., Ohrling, G., Larsson, R., Patel, M., Weise, C.B., Rye, K.-A., Vickers, K.C., and Tabet, F.

High density lipoproteins induce miR-223-3p biogenesis and export form myeloid cells—role of scavenger receptor B1-mediated transfer.

Atherosclerosis. In press. Date of Acceptance: May 1, 2019

Ong, K.L., Campbell, S., Wu, B.J., McLelland, R.L., Kokkinos, J., Szlko, M., Polak, J.F., Allison, M.A., Rye, K.-A.

Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis.

Atherosclerosis. In press. Date of Acceptance: June 7, 2019

Grants & Funding

Students

  • Bikash Manandhar
  • Veronica Truong
  • Thomas King
  • Bradley Tucker
  • Jack Ang
  • Marlon Randeniya
  • Shivam Patel