About us
The Cardiovascular and Metabolic Disease Research Group is co-led by Prof. Kerry-Anne Rye and A/Prof. Shane Thomas. The research group consists of 4 post-doctoral scientists, 3 PhD students and 4 honours students. The group has two main research themes:
Heart disease
We are developing new anti-inflammatory therapies that prevent the development of atherosclerotic lesions, which can rupture and stop blood from getting to the heart, causing a heart attack. We are also asking whether these anti-inflammatory therapies can heal the tissue damage that is caused by a heart attack.
In particular, we are complexing a new class of nanoparticles with clinically viable peptides and small molecule drugs that inhibit inflammation and oxidative stress in the heart and blood vessels. We envisage that these new nanotherapeutics will reduce the risk of having a heart attack and stop tissue damage of a heart attack does occur. The research uses biochemical and molecular biology techniques as well as novel pre-clinical models of cardiovascular disease and crosses the disciplines of pharmacology and vascular biology.
We are also studying the molecular mechanisms by which vascular endothelial cells transform into pro-inflammatory mesenchymal-like cells via the process of endothelial-to-mesenchymal (EndMT). EndMT promotes the development of rupture-prone atherosclerotic lesions and we have identified new molecular signaling events driving this process that will inform the discovery of new treatments for inhibiting EndMT in cardiovascular disease. This project involves biochemistry, as well as cell and molecular biology.
Type 1 diabetes
Type 1 diabetes is an autoimmune disease in which insulin-producing cells in the pancreas are destroyed by activated T-cells and glucose can no longer be removed from blood. There is no cure for this disease, with the only treatment being regulation of blood glucose levels by multiple insulin injections every day. However, these injections can reduce blood glucose levels to an extent that is potentially lethal. Moreover, they treat the symptoms, not the underlying cause of the disease.
We have identified a peptide with the capacity to regenerate new insulin-producing cells in the pancreas and stop T-cell expansion, thus decreasing, and possibly removing, the dependence of patients with type 1 diabetes on insulin injections. Further development of this project towards clinical translation involves multiple skill sets including molecular biology, pharmacology. We are also developing strategies for oral peptide delivery, and using gold-standard pre-clinical models of type 1 diabetes.
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.
- Identification of novel biomarkers as predictors of cardiovascular risk.
- Treating diabetes-accelerated atherosclerosis with immune nanoparticles.
Research opportunities
There are opportunities for Honours, PhD and ILP students: contact Prof Kerry-Anne Rye for details of specific projects.
Team
Co-Lead Cardiovascular and Metabolic Disease Research Group
Kerry-Anne Rye
T: +61 2 9385 1219
E: k.rye@unsw.edu.au
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Co-Lead Cardiovascular and Metabolic Disease Research Group
Shane Thomas
E: shane.thomas@unsw.edu.au
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Research Assistant
Bikash Manandhar
E: b.manandhar@unsw.edu.au
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Collaborators
- Dr Gary Ren, Lawrence Berkeley Laboratory, CA, USA.
HDLstructure and function
Interactions of HDLs and cholesteryl ester transfer protein - Dr Alan Remaley, NHLBI, Bethesda, MD, USA
Regulation of HDL function by mimetic peptides - A/Prof Veronique Angeli, National University of Singapore
ApoA-I and lymphatic biology - Dr Roshni Singaraja, A*Star, Singapore
Role of ABCA8 in cardiometabolic disease - Nick King, University of Sydney
- Laurence Macia, University of Sydney
- Pall Thordarson, UNSW
- Mark Hulett, La Trobe University
Resources & tools
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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, 2019Hackett, 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
Postdoctoral students
- Elias Glaros
- Jacqueline Ku
- Carmen Zhang
- Ben Wu
Students
- Thomas King
- Samson Ogumodede
- Vaishnavi Ratnasabesar
- Deanne Do Rosario
- Claudia Fanuli
- Fatima El Najaar