Little Group - Kidney Development
The kidney is a complex organ responsible not only for removal of nitrogenous wastes but for the regulation of fluid balance, pH, blood pressure, red blood cell count and bone density. Each kidney contains 300,000 to 1.8 million functional filtration units; the nephrons with the capacity for the kidney to function determined by total nephron number. Nephron formation in the human kidney ends around birth as the nephron stem cell population disappears. How these stem cells are regulated to form nephrons and why they disappear is not known. However, regulating or recreating these cells is essential for kidney regeneration.
Organ regeneration rests on an understanding of how the organ forms normally. The discoveries Professor Little and her group have made in normal nephron development are being harnessed for the development of novel approaches to kidney regeneration. This includes the generation of stem cells for rebuilding of repairing the damaged organ, as well as creating mini-kidneys for use in drug screening and disease modelling.
More information about the Little group at the University of Copenhagen will be added soon.
Understanding the regulation of kidney morphogenesis in order to improve renal development
(2013–2016) NHMRC Project Grant
Kidney mesenchymal stem cells in tubular development, repair and turnover
(2012–2017) NHMRC European Union Collaborative Research Grant
Stem-Cell Based Therapy for Kidney Repair
(2012–2017) European Commission 7th Framework Programme, Stellar Consortium
Directed differentiation of human embryonic stem cells to kidney progenitors
(2012–2015) NHMRC Project Grant
Kidney mesenchymal stem cells in tubular development, repair and turnover
(2012–2015) NHMRC Project Grant
Reprogramming to generate new nephron progenitors
(2012–2015) NHMRC Project Grant
Understanding self-organizing tissues
(2012–2015) ARC Discovery Project
Stem Cells Australia
(2011–2018) ARC Special Research Initiative
How to build a kidney: quantitative modelling of kidney morphogenesis across time and space
(2011–2014) Human Frontier Science Program Organisation Grant
GUDMAP - Database and Website
(2011–2015) National Institutes of Health Grant
Lawlor, K. T., Vanslambrouck, J. M., Higgins, J. W., Chambon, A., Bishard, K., Arndt, D., Er, P. X., Wilson, S. B., Howden, S. E., Tan, K. S., Li, F., Hale, L. J., Shepherd, B., Pentoney, S., Presnell, S. C., Chen, A. E., & Little, M. H. (2021). Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nature Materials, 20(2), 260–271. doi: 10.1038/s41563-020-00853-9.
Howden, S. E., Wilson, S. B., Groenewegen, E., Starks, L., Forbes, T. A., Tan, K. S., Vanslambrouck, J. M., Holloway, E. M., Chen, Y. H., Jain, S., Spence, J. R., and Little, M. H. (2021). Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk. Cell Stem Cell, 28(4), 671–684.e6.
Phipson, B., Er, P. X., Combes, A. N., Forbes, T. A., Howden, S. E., Zappia, L., Yen, H. J., Lawlor, K. T., Hale, L. J., Sun, J., Wolvetang, E., Takasato, M., Oshlack, A., and Little, M. H. (2019). Evaluation of variability in human kidney organoids. Nature Methods, 16(1), 79–87. doi: 10.1038/s41592-018-0253-2.
Forbes, T. A., Howden, S. E., Lawlor, K., Phipson, B., Maksimovic, J., Hale, L., Wilson, S., Quinlan, C., Ho, G., Holman, K., Bennetts, B., Crawford, J., Trnka, P., Oshlack, A., Patel, C., Mallett, A., Simons, C., and Little, M. H. (2018). Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype and Reveal Underlying Pathogenetic Mechanisms. American Journal of Human Genetics, 102(5), 816–831. doi: 10.1016/j.ajhg.2018.03.014.
van den Berg, C. W., Ritsma, L., Avramut, M. C., Wiersma, L. E., van den Berg, B. M., Leuning, D. G., Lievers, E., Koning, M., Vanslambrouck, J. M., Koster, A. J., Howden, S. E., Takasato, M., Little, M. H., & Rabelink, T. J. (2018). Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo. Stem Cell Reports, 10(3), 751–765. doi: 10.1016/j.stemcr.2018.01.041.
Takasato, M., Er, P. X., Chiu, H. S., Maier, B., Baillie, G. J., Ferguson, C., Parton, R. G., Wolvetang, E. J., Roost, M. S., Chuva de Sousa Lopes, S. M., and Little, M. H. (2015). Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature, 526(7574), 564–568. doi: 10.1038/nature15695.
Takasato, M., Er, P. X., Becroft, M., Vanslambrouck, J. M., Stanley, E. G., Elefanty, A. G., and Little, M. H. (2014). Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nature Cell Biology, 16(1), 118–126. doi: 10.1038/ncb2894.
Short, K. M., Combes, A. N., Lefevre, J., Ju, A. L., Georgas, K. M., Lamberton, T., Cairncross, O., Rumballe, B. A., McMahon, A. P., Hamilton, N. A., Smyth, I. M., and Little, M. H. (2014). Global quantification of tissue dynamics in the developing mouse kidney. Developmental Cell, 29(2), 188–202. doi: 10.1016/j.devcel.2014.02.017.
Brunskill, E. W., Aronow, B. J., Georgas, K., Rumballe, B., Valerius, M. T., Aronow, J., Kaimal, V., Jegga, A. G., Yu, J., Grimmond, S., McMahon, A. P., Patterson, L. T., Little, M. H., and Potter, S. S. (2008). Atlas of gene expression in the developing kidney at microanatomic resolution. Developmental Cell, 15(5), 781–791. doi: 10.1016/j.devcel.2008.09.007.
Bickmore, W. A., Oghene, K., Little, M. H., Seawright, A., van Heyningen, V., and Hastie, N. D. (1992). Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science, 257(5067), 235–237. doi: 10.1126/science.1321494.
Research Profile
Professor Melissa Little, BSc (Hons I), PhD, GAICD, FAAHMS, FAAS, is the CEO of the Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Executive Director of reNEW Copenhagen. Internationally recognised for her work on kidney development and her pioneering studies into potential regenerative therapies in the kidney, Professor Little’s approach to generating kidney organoids from human pluripotent stem cells has been adopted across the globe where it is being applied to disease modelling, drug screening and renal replacement therapies. Founded on >30 years of fundamental developmental biology, her stem cell research illustrates the capacity for understanding to be applied to product development.
Currently President of the International Society for Stem Cell Research, Professor Little also leads the renal regeneration laboratory at the Murdoch Childrens Research Institute, Melbourne, and holds an honorary position as Professor in the Department of Pediatrics, University of Melbourne. Professor Little’s work has been recognised by many awards, including the GlaxoSmithKline Award for Research Excellence (2005), an Eisenhower Fellowship (2006), Eureka Prize (2016). Of note, she was awarded the Alfred Newton Richards Award from the International Society for Nephrology (2018) for her kidney organoid research, the Julian Wells Medal (2020) for her contribution to understanding of genetic basis of kidney development and the Homer W. Smith Award (2021) for her outstanding contributions that fundamentally affect the science of nephrology.
Professor Little is a Fellow of the Australian Academy of Science and the Australian Academy of Health and Medical Sciences, and Associate Editor for the Journal of the American Society for Nephrology and is on the editorial board of the Cell Stem Cell, Nature Reviews Nephrology, Development and Kidney International. Melissa has previously held the role of President of the Australasian Society for Stem Cell Research, Program Leader of Stem Cells Australia, and the Chief Scientific Officer of the Australian Stem Cell Centre.
Curriculum Vitae
1990-1992 Royal Society Endeavour Fellow, MRC Human Genetics Unit, Edinburgh, Scotland.
1992-1994 Endeavour Postdoctoral Fellow, University of Queensland (UQ)
1995-1997 Project Leader - NHMRC R. Douglas Wright Fellow, CMCB, UQ
- Sylvia and Charles Viertel Senior Research Fellow, CMCB,UQ
2003-2004 NHMRC Senior Research Fellow, UQ
2005-2006 NHMRC Principal Research Fellow, UQ
2007-2008 Chief Scientific Officer, Australian Stem Cell Centre
2009-2012 NHMRC Principal Research Fellow, Institute for Molecular Bioscience, UQ
2013-2014 NHMRC Senior Principal Research Fellow, Institute for Molecular Bioscience, UQ
2015-2022 NHMRC Senior Principal Research Fellow, Murdoch Children’s Research Institute
2021 Homer Smith Award, American Society for Nephrology
2020 Julian Wells Medal
2019 Alfred Richards Newton Award, International Society for Nephrology
2019 Doctor Honoris Causa, Leiden University
2018 NHMRC Elizabeth Blackburn Fellowship Biomedical
2018 NHMRC Top Research Fellowship
2017 UQ Alumnus of the Year
2017 Fellow, Australian Academy of Science
2016 Fellow, Australian Academy of Health and Medical Sciences
2016 Eureka Prize
Staff List - Little Group
| Name | Title | Job responsibilities | Phone | |
|---|---|---|---|---|
| Search in Name | Search in Title | Search in Job responsibilities | Search in Phone | |
| Flett, Helen | External | |||
| Frænde, Gitte | Administrative Officer | +4535329275 | ||
| Little, Melissa Helen | Professor | +4535325580 | ||
| Løkkegaard, Jeanette | Research Consultant | |||
| Munaretto, Jacopo | Research Assistant | +4535328686 | ||
| Paz Santos, Inês | Research Assistant | +4535329938 | ||
| Werner, Rikke Elise | Administrative Officer | +4535328977 | ||
| Wildfang, Louise Menck | Research Assistant | +4535327651 | ||
| Wilson, Sean Benjamin | Postdoc |