Dr. Alex Smith is a Research Fellow at UQ's School of Chemical Engineering. His interests are in understanding structure: function relationships between complex carbohydrates (such as heparan sulphate) and proteins, and how these interactions can inform the development of glycotherapeutic agents to treat a wide varienty of injuries and diseases.
Journal Article: Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic
Smith, Raymond A. A., Luo, Xiaoman, Lu, Xiaohua, Tan, Tuan Chun, Le, Bach Q., Zubkova, Olga V., Tyler, Peter C., Nurcombe, Victor and Cool, Simon M. (2023). Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic. Biomaterials Advances, 155 213671, 1-17. doi: 10.1016/j.bioadv.2023.213671
Journal Article: Affinity-selected heparan sulfate collagen device promotes periodontal regeneration in an intrabony defect model in Macaca fascicularis
Luo, Xiaoman, Lau, Chau Sang, Le, Bach Quang, Tan, Tuan Chun, Too, Jian Hui, Smith, Raymond Alexander Alfred, Yu, Na and Cool, Simon M. (2023). Affinity-selected heparan sulfate collagen device promotes periodontal regeneration in an intrabony defect model in Macaca fascicularis. Scientific Reports, 13 (1) 11774, 1-15. doi: 10.1038/s41598-023-38818-y
Journal Article: Bioactive polyethylene by ring opening metathesis polymerization for potential orthopaedic applications
Guo, Jiayi, Park, Eun Ju, Teo, Yew Chin, Abbas, Asyraf, Goh, Denise, Smith, Raymond Alexander Alfred, Nie, Yuntong, Nguyen, Hang T. L., Yeong, Joe Poh Sheng, Cool, Simon, Haruyuki, Makio and Teo, Peili (2023). Bioactive polyethylene by ring opening metathesis polymerization for potential orthopaedic applications. Polymer Chemistry, 14 (15), 1743-1751. doi: 10.1039/d2py01545e
Developing novel glycan-functionalised composite biomaterials for improving bone formation
Heparan sulphate (HS) plays key roles in many biological processes, including wound healing, as it binds and protects critical pro-regenerative factors within a wound site. HS-functionalised biomaterials have shown promise in enhancing the endogenous wound healing response in various models, including bone repair.
This project aims to investigate novel methods for functionalising common biomaterials used in bone repair (such as (poly)caprolactone and hydroxyapatite) with HS using several different grafting strategies. These novel, glycan-functionalised biomaterials will then be characterised extensively using chemical, physical, biophysical, and biological techniques to assess structure, function, and ability to enhance osteogenesis.
Adult stem cells offer great potential as a cell therapy through the secretion of immunomodulatory factors. However, understanding what mechanisms underpin the regulation of these factors and the balance between a pro- and anti-inflammatory secretome remains to be elucidated. Using induced pluripotent stem cell-derived adult stem cells from different genomic backgrounds, this project will use biochemical and molecular techniques to identify changes in the secretion of pro- and anti-inflammatory factors through continuous in vitro culture. The performance of these stem cells will be assessed using in vitro and potentially in vivo models of inflammation and inflammatory disease. Finally, correlation between genomic background and immunomodulatory performance will be established, offering crucial insight into the generation of future cell therapies.
Glycocalyx remodeling with glycopolymer-based proteoglycan mimetics
Huang, Mia L., Smith, Raymond A. A., Trieger, Greg W. and Godula, Kamil (2016). Glycocalyx remodeling with glycopolymer-based proteoglycan mimetics. Macro-glycoligands: methods and protocols. (pp. 207-224) edited by Xue-Long Sun. New York, NY, United States: Humana Press. doi: 10.1007/978-1-4939-3130-9_17
Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic
Smith, Raymond A. A., Luo, Xiaoman, Lu, Xiaohua, Tan, Tuan Chun, Le, Bach Q., Zubkova, Olga V., Tyler, Peter C., Nurcombe, Victor and Cool, Simon M. (2023). Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic. Biomaterials Advances, 155 213671, 1-17. doi: 10.1016/j.bioadv.2023.213671
Luo, Xiaoman, Lau, Chau Sang, Le, Bach Quang, Tan, Tuan Chun, Too, Jian Hui, Smith, Raymond Alexander Alfred, Yu, Na and Cool, Simon M. (2023). Affinity-selected heparan sulfate collagen device promotes periodontal regeneration in an intrabony defect model in Macaca fascicularis. Scientific Reports, 13 (1) 11774, 1-15. doi: 10.1038/s41598-023-38818-y
Guo, Jiayi, Park, Eun Ju, Teo, Yew Chin, Abbas, Asyraf, Goh, Denise, Smith, Raymond Alexander Alfred, Nie, Yuntong, Nguyen, Hang T. L., Yeong, Joe Poh Sheng, Cool, Simon, Haruyuki, Makio and Teo, Peili (2023). Bioactive polyethylene by ring opening metathesis polymerization for potential orthopaedic applications. Polymer Chemistry, 14 (15), 1743-1751. doi: 10.1039/d2py01545e
Bioactive PCL-peptide and PLA-peptide brush copolymers for bone tissue engineering
Teo, Yew Chin, Park, Eun Ju, Guo, Jiayi, Abbas, Asyraf, Smith, Raymond Alexander Alfred, Goh, Denise, Yeong, Joe Poh Sheng, Cool, Simon and Teo, Peili (2022). Bioactive PCL-peptide and PLA-peptide brush copolymers for bone tissue engineering. ACS Applied Bio Materials, 5 (10), 4770-4778. doi: 10.1021/acsabm.2c00455
Srinivasan, Akshaya, Sathiyanathan, Padmapriya, Yin, Lu, Liu, Tong Ming, Lam, Alan, Ravikumar, Maanasa, Smith, Raymond Alexander Alfred, Loh, Han Ping, Zhang, Ying, Ling, Ling, Ng, Say Kong, Yang, Yuan Sheng, Lezhava, Alexander, Hui, James, Oh, Steve and Cool, Simon M. (2022). Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion. Cytotherapy, 24 (5), 456-472. doi: 10.1016/j.jcyt.2021.11.009
Variability in the composition of porcine mucosal heparan sulfates
Sargison, Liam, Smith, Raymond A A, Carnachan, Susan M, Daines, Alison M, Brackovic, Amira, Kidgell, Joel T, Nurcombe, Victor, Cool, Simon M, Sims, Ian M and Hinkley, Simon F R (2022). Variability in the composition of porcine mucosal heparan sulfates. Carbohydrate Polymers, 282 119081, 119081. doi: 10.1016/j.carbpol.2021.119081
Application of a BMP2-binding heparan sulphate to promote periodontal regeneration
Le, B. Q., Too, J. H., Tan, T. C., Smith, R. A. A., Nurcombe, , Cool, S. M. and Yu, N. (2021). Application of a BMP2-binding heparan sulphate to promote periodontal regeneration. European Cells and Materials, 42, 139-153. doi: 10.22203/eCM.v042a10
Heparan sulfate proteoglycans: key mediators of stem cell function
Ravikumar, Maanasa, Smith, Raymond Alexander Alfred, Nurcombe, Victor and Cool, Simon M. (2020). Heparan sulfate proteoglycans: key mediators of stem cell function. Frontiers in Cell and Developmental Biology, 8 581213, 581213. doi: 10.3389/fcell.2020.581213
Chan, Su Jing, Esposito, Elga, Hayakawa, Kazuhide, Mandaville, Emiri, Smith, Raymond A. A., Guo, Shuzhen, Niu, Wanting, Wong, Peter Tsun-Hong, Cool, Simon M., Lo, Eng H. and Nurcombe, Victor (2020). Vascular endothelial growth factor 165-binding heparan sulfate promotes functional recovery from cerebral ischemia. Stroke, 51 (9), 2844-2853. doi: 10.1161/STROKEAHA.119.025304
A synthetic heparan sulphate mimetic for enhancing BMP-2-mediated osteogenesis and bone regeneration
Smith, R.A., Lu, X., Tan, T., Luo, X., Le, B.Q., Zubkova, O.V., Cool, S. and Nurcombe, V. (2020). A synthetic heparan sulphate mimetic for enhancing BMP-2-mediated osteogenesis and bone regeneration. Cytotherapy, 22 (5), S32-S32. doi: 10.1016/j.jcyt.2020.03.017
Enhancing the efficacy of stem cell therapy with glycosaminoglycans
Ling, Ling, Ren, Xiafei, Cao, Xue, Hassan, Afizah Binte Mohd, Mah, Sophia, Sathiyanathan, Padmapriya, Smith, Raymond A. A., Tan, Clarissa L. L., Eio, Michelle, Samsonraj, Rebekah M., Van Wijnen, Andre J., Raghunath, Michael, Nurcombe, Victor, Hui, James H. and Cool, Simon M. (2020). Enhancing the efficacy of stem cell therapy with glycosaminoglycans. Stem Cell Reports, 14 (1), 105-121. doi: 10.1016/j.stemcr.2019.12.003
Nurcombe, Victor, Ling, Ling, Hondermarck, Hubert, Cool, Simon M. and Smith, Raymond A. A. (2019). Bringing heparan sulfate glycomics together with proteomics for the design of novel therapeutics: A historical perspective. Proteomics, 19 (21-22) 1800466, 1800466. doi: 10.1002/pmic.201800466
A heparan sulfate device for the regeneration of osteochondral defects
Lee, Jonathan H., Luo, Xiaoman, Ren, Xiafei, Tan, Tuan Chun, Smith, Raymond A.A., Swaminathan, Kunchithapadam, Sekar, Sakthivel, Bhakoo, Kishore, Nurcombe, Victor, Hui, James H. and Cool, Simon M. (2019). A heparan sulfate device for the regeneration of osteochondral defects. Tissue Engineering - Part A, 25 (5-6), 352-363. doi: 10.1089/ten.tea.2018.0171
Dendrimer heparan sulfate glycomimetics: potent heparanase inhibitors for anticancer therapy
Zubkova, Olga V., Ahmed, Yassir A., Guimond, Scott E., Noble, Sophia-Louise, Miller, John Holmes, Smith, Raymond Alexander Alfred, Nurcombe, Victor, Tyler, Peter C., Weissmann, Marina, Vlodavsky, Israel and Turnbull, Jeremy E. (2018). Dendrimer heparan sulfate glycomimetics: potent heparanase inhibitors for anticancer therapy. ACS Chemical Biology, 13 (12), 3236-3242. doi: 10.1021/acschembio.8b00909
Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate
Poon, Selina, Lu, Xiaohua, Smith, Raymond A. A., Ho, Pei, Bhakoo, Kishore, Nurcombe, Victor and Cool, Simon M. (2018). Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate. Angiogenesis, 21 (4), 777-791. doi: 10.1007/s10456-018-9622-9
Minimum structural requirements for BMP-2-binding of heparin oligosaccharides
Smith, Raymond A.A., Murali, Sadasivam, Rai, Bina, Lu, Xiaohua, Lim, Zophia Xue Hui, Lee, Jaslyn J.L., Nurcombe, Victor and Cool, Simon M. (2018). Minimum structural requirements for BMP-2-binding of heparin oligosaccharides. Biomaterials, 184, 41-55. doi: 10.1016/j.biomaterials.2018.08.056
Retention of the structure and function of heparan sulfate biomaterials after gamma irradiation
Smith, Raymond A.A., Chua, R. J.E., Carnachan, Susan M., Tan, Clarissa L.L., Sims, Ian M., Hinkley, Simon F.R., Nurcombe, Victor and Cool, Simon M. (2018). Retention of the structure and function of heparan sulfate biomaterials after gamma irradiation. Tissue Engineering - Part A, 24 (9-10), 729-739. doi: 10.1089/ten.tea.2017.0263
Huang, Mia L., Michalak, Austen L., Fisher, Christopher J., Christy, Mitchell, Smith, Raymond A. A. and Godula, Kamil (2018). Small molecule antagonist of cell surface glycosaminoglycans restricts mouse embryonic stem cells in a pluripotent state. Stem Cells, 36 (1), 45-54. doi: 10.1002/stem.2714
Ayerst, Bethanie I., Smith, Raymond A.A., Nurcombe, Victor, Day, Anthony J., Merry, Catherine L.R. and Cool, Simon M. (2017). Growth differentiation factor 5-mediated enhancement of chondrocyte phenotype is inhibited by heparin: implications for the use of heparin in the clinic and in tissue engineering applications. Tissue Engineering - Part A, 23 (7-8), 275-292. doi: 10.1089/ten.tea.2016.0364
Determining the extent of heparan sulfate depolymerisation following heparin lyase treatment
Carnachan, Susan M., Bell, Tracey J., Sims, Ian M., Smith, Raymond A.A., Nurcombe, Victor, Cool, Simon M. and Hinkley, Simon F.R. (2016). Determining the extent of heparan sulfate depolymerisation following heparin lyase treatment. Carbohydrate Polymers, 152, 592-597. doi: 10.1016/j.carbpol.2016.07.024
Lee, Jonathan, Wee, Sheena, Gunaratne, Jayantha, Chua, R. J. E., Smith, Raymond A. A., Ling, Ling, Fernig, David G., Swaminathan, Kunchithapadam, Nurcombe, Victor and Cool, Simon M. (2015). Structural determinants of heparin-transforming growth factor-β1 interactions and their effects on signaling. Glycobiology, 25 (12), 1491-1504. doi: 10.1093/glycob/cwv064
Holley, Rebecca J., Smith, Raymond A., van de Westerlo, Els M. A., Pickford, Claire E., Merry, C. L. R. and van Kuppevelt, Toin H. (2015). Use of flow cytometry for characterization and fractionation of cell populations based on their expression of heparan sulfate epitopes. Glycosaminoglycans: Chemistry and Biology, 1229, 239-251. doi: 10.1007/978-1-4939-1714-3_21
Huang, Mia L., Smith, Raymond A. A., Trieger, Greg W. and Godula, Kamil (2014). Glycocalyx remodeling with proteoglycan mimetics promotes neural specification in embryonic stem cells. Journal of the American Chemical Society, 136 (30), 10565-10568. doi: 10.1021/ja505012a
Glycosaminoglycans as regulators of stem cell differentiation
Smith, Raymond A. A., Meade, Kate, Pickford, Claire E., Holley, Rebecca J. and Merry, Catherine L. R. (2011). Glycosaminoglycans as regulators of stem cell differentiation. Biochemical Society Transactions, 39 (1), 383-387. doi: 10.1042/bst0390383
Ling, L., Ren, X., Hassan, A. Binte Mohd, Mah, S., Smith, R. A., Tan, C., van Wijnen, A., Raghunath, M., Nurcombe, V., Hui, J. and Cool, S. (2019). Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells. ISCT 2019, Melbourne, VIC, Australia, 29 May - 1 June 2019. Oxford, United Kingdom: Elsevier. doi: 10.1016/j.jcyt.2019.03.463
Harnessing glycocalyx interactions to modulate differentiation and development
Huang, Mia L., Michalak, Austen L., Tota, Ember M., Smith, Raymond Alexander, Trieger, Greg W. and Godula, Kamil (2018). Harnessing glycocalyx interactions to modulate differentiation and development. Experimental Biology 2018 Meeting, San Diego, CA United States, 21-25 April 2018. Hoboken, NJ United States: John Wiley & Sons. doi: 10.1096/fasebj.2018.32.1_supplement.673.16
Glycocalyx based strategies to modulate embryonic stem cell fates
Huang, Mia, Godula, Kamil, Smith, Raymond, Christy, Mitchell, Fisher, Christopher and Michalak, Austen (2016). Glycocalyx based strategies to modulate embryonic stem cell fates. Washington, DC, United States: American Chemical Society.
Godula, Kamil, Huang, Mia, Smith, Raymond and Trieger, Greg (2014). Glycocalyx remodeling with synthetic proteoglycan mimetics promotes neural specification in embryonic stem cells. Joint Meeting of the Society-for-Glycobiology (SFG) and the Japanese-Society-of-Carbohydrate-Research (JSCR), Honolulu, HI, United States, 16-19 November 2014. Cary, NC, United States: Oxford University Press.
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
Developing novel glycan-functionalised composite biomaterials for improving bone formation
Heparan sulphate (HS) plays key roles in many biological processes, including wound healing, as it binds and protects critical pro-regenerative factors within a wound site. HS-functionalised biomaterials have shown promise in enhancing the endogenous wound healing response in various models, including bone repair.
This project aims to investigate novel methods for functionalising common biomaterials used in bone repair (such as (poly)caprolactone and hydroxyapatite) with HS using several different grafting strategies. These novel, glycan-functionalised biomaterials will then be characterised extensively using chemical, physical, biophysical, and biological techniques to assess structure, function, and ability to enhance osteogenesis.
Adult stem cells offer great potential as a cell therapy through the secretion of immunomodulatory factors. However, understanding what mechanisms underpin the regulation of these factors and the balance between a pro- and anti-inflammatory secretome remains to be elucidated. Using induced pluripotent stem cell-derived adult stem cells from different genomic backgrounds, this project will use biochemical and molecular techniques to identify changes in the secretion of pro- and anti-inflammatory factors through continuous in vitro culture. The performance of these stem cells will be assessed using in vitro and potentially in vivo models of inflammation and inflammatory disease. Finally, correlation between genomic background and immunomodulatory performance will be established, offering crucial insight into the generation of future cell therapies.