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
Co-Lead Cardiovascular and Metabolic Disease Research Group

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
Co-Lead Cardiovascular and Metabolic Disease Research Group

E: shane.thomas@unsw.edu.au

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Research Assistant

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

  • 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

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