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Transcriptional Regulation of Vessels Laboratory

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Francois Laboratory

  • Mat Francois from the Francois Laboratory
    Mat Francois
    Principal Investigator Read more
    Cathy Pichol-Thievend
    PostDoctoral Researcher Read more
    Frank Fontaine
    PostDoctoral Researcher Read more
    Ivy Chiang
    PhD student Read more
    Emmanuelle Frampton
    Research Assistant Read more
    Renae Skoczylas
    Research Assistant Read more
    Alex McCann
    PhD student Read more
    Xiaojun Yu
    PhD student
    Keyi Jiang
    PhD student

Lymphatic vessels are a vital component of the vascular system and are essential for immune surveillance and maintaining fluid balance. In the adult, aberrant formation of lymphatic vessels is associated with a wide range of diseases that include chronic inflammatory disorders, cancer metastasis and lymphoedema. The vasculature is also centrally important in cardiovascular diseases and cancer progression. We aim to better understand how the vasculature forms during development and to translate our findings into a deeper understanding of disease. We study several aspects of vascular development and biology.

The Francois laboratory, is located at the Institute for Molecular Bioscience.  Our research identifies and characterises transcriptional pathways influencing blood and lymphatic vascular development in vertebrates. We are using a combination of developmental model systems and pre-clinical mouse models of cancer or lymphoedema to validate the central role of transcriptional regulators that are reactivated in these diseases. A section of our research program also focuses around transcription factor druggability. This approach will help us to develop a new class of compounds that will enable the pharmacological management of the vascular tree. This strategy has been designed to establish a new basis for drug discovery. We have published our research in journals such as Nature, PNAS, Blood, Elife and Cell Chemical Biology.

The Francois Lab

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Francois lab research

Research in the lab focuses on key molecular switches (transcription factors, TFs) that instruct the morphogenesis and the specification of endothelial cells during embryogenesis. Discoveries in this area are crucial in the long-term since they will enable us to develop new tools to complement classic genetic approaches (gain or loss of function) with pharmacology. This strategy has the potential to unlock the identification and characterization of novel druggable molecular targets.


Cellular and molecular origin of lymphatic endothelial precursors

Based on the initial discovery of the role of SOX18 transcription factor to induce lymphatic endothelial cell specification in venous progenitors cells our effort focus on deciphering the molecular fine-tuning of SOX-F transcription factor activity. We also developed fate mapping strategies to identify potential non-endothelial cell origin of LEC precursors in various organs. This approach is mostly performed using mouse genetics, but also in close collaboration with Hogan and Smith Labs to take full advantage of the zebrafish model system.


Francois lab research

Defining novel molecular targets to manipulate vessel growth

One central interest of the lab is to better our understanding of the molecular mode of action of transcription factors, more particularly SOX-F proteins. We have now developed a new toolkit that enables to gauge in high throughput manner in vitro in homogenous assays and in vivo potential TFs interactions that instruct endothelial cell differentiation. These assays are also being used as basis to perform drug screen and identify new small molecules that can modulate angio- and lymphangiogenesis in mouse and zebrafish.


We partner with industry, such as Pylogica and CSL, to develop novel approaches to manipulate SOX TF activity with the view to unlocking new classes of therapeutics to manage vascular related disorders.

Mat Francois laboratory image

Modeling diseases, harvesting lymphatic growth to block solid tumour metastasis

Lymphatic vessels outgrowth is one of the hallmark for solid cancer prior to the onset of metastasis. The recent identification of the role of SOX18 in this process led us to investigate more in the depth potential regulation of the activity of this TF in the context of tumour-induced neo-lymphangiogenesis. We are also currently testing a novel generation of small molecules inhibitors that can block SOX18 validate this TF as a molecular target and establish a proof of principle that TF are druggable proteins.







Examining an extracellular matrix regulator required for cardiovascular development
2016-2019, NHMRC Project Grant
Collaboration: Dr Kelly Smith, Dr Mathias Francois, AProf Carol Wicking, Dr Enzo Porrello, Dr Ben Hogan


Deciphering the transcriptional program that instructs lymphatic endothelial cell fate
2016-2018, NHMRC Project Grant
Dr Mathias Francois


Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis
2016-2018, NHMRC Project Grant
Collaboration: Dr Ben Hogan, Dr Cas Simons, Dr Kelly Smith, Dr Mathias Francois, Dr Gregory Baillie, Prof Peter Koopman


SOX18-VEGF cross regulation during angiogenesis and blood vascular development
2016-2017, Cancer Council Queensland Project Grant
Collaboration: Dr Mathias Francois, Dr Ben Hogan, Prof Peter Koopman


Targeting the undruggable: epitope mapping using Pylomers peptides to modulate activity of Transcription Factors
2016-2018, ARC Linkage Project with Phylogica


A critical new signalling axis in lymphatic vascular angiogenesis
2015-2017, NHMRC Project Grant
Collaborators: Dr Ben Hogan, Dr Mathias Francois


Role of resident endothelial progenitor cells in melanoma vascularisation and progression
2015-2017, NHMRC Project Grant
Collaborators: AProfessor Kiarash Khosrotehrani, Dr Mathias Francois

Deciphering the cellular functions of caveolae that govern lymphatic vascular development
2014-2016, ARC Discovery Project
Collaborators: Dr Mathias Francois, Associate Professor Marie-Odile Parat


Functional and molecular characterization of a novel regulator of angiogenesis
2013-2016, NHMRC Project Grant
Collaborators: Dr Kelly Smith, Dr Ben Hogan, Dr Mathias Francois





Uncovering the cellular origin of lymphatic endothelial progenitors in cancer model systems
PhD project: Ivy Chiang


Transcriptional regulation of endothelial cell fate
PhD project: Xiaojun Yu


Heterogeneity and clonal expansion of the developing vasculature
PhD project: Keyi Jiang


Cellular origin of the developing lymphatics
Cathy Pichol Thievend


Small molecule inhibitors of the SOX18 transcription factor
Frank Fontaine


Defining genetic and biomechanical regulators of cardiac looping
PhD project. Primary Supervisor: Kelly Smith





Uncovering a novel genetic interaction that governs blood vessel development in health and disease
2013-2015, NHMRC Project Grant
Collaborators: Dr Mathias Francois, Dr Ben Hogan


Uncovering genetic interactions that govern lymphangiogenesis in mouse and fish: a strategy to reveal the basis of lymphatic vascular disorders
2013-2015, Universita degli Studi di Milano, CARIPLO Foundation, Italy
Collaborators: Dr Mathias Francois, Dr Ben Hogan





National Collaborations

Marc Achen and Steven Stacker
The Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA
The cross regulation of SOX18 ad VEGFD during angiogenesis.

Yann Gambin and Emma Sierecki
University of New South Wales, Sydney, AUSTRALIA
Applications of single molecule fluorescence.

Natasha Harvey
Centre for Cancer Biology, SA Pathology, Adelaide, AUSTRALIA
Long-term collaborations in developmental lymphatics.

Ben Hogan
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Long-term collaborations in zebrafish and vascular biology.

Kelly Smith
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Examining an extracellular matrix regulator of cardiovascular development.

Kiarash Khosrotehrani
Diamantina Institute, the University of Queensland, Brisbane, AUSTRALIA
Role of resident endothelial progenitor cells in melanoma vascularisation and progression.

Peter Koopman
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Characterisation of a divergent model of lymphangiogensis in the developing gonads.

Marie-Odile Parat
Pharmacy Australia Centre of Excellence, the University of Queensland, Brisbane, AUSTRALIA
Deciphering the cellular functions of caveolae that govern lymphatic vascular development. Characterisation of caveolin function in prostate cancer-induced lymphangiogenesis.

International Collaborations


Monica Beltrame and Franco Coteli

University of Milan, Milan, ITALY
Characterisation of the heat shock inducible Sox18–Ragged zebrafish phenotype.

Jason Carrol
Cancer Research UK Cambridge Institute, Cambridge, UNITED KINGDOM
CHIP-seq approaches to survey Sox18 binding activity on a genome wide scale during zebrafish vascular development.

Elisabetta Dejana
Sox F and vascular development.

Sarah De Val
Ludwig Institute, Oxford, UK
Characterisation of endothelial specific regulatory elements.


Commercial Collaborations


Investigations into the SOX18 interactome and novel methods of manipulating protein-protein interactions during vascular development.


Melbourne, AUSTRALIA
Under the umbrella of the UQ ARC Centre for BioPharmaceutical Innovations.


Developing intra-cellular antibodies to target SOX18 transcription factor activity.







Francois lab discoveries in the media




17 Feb 2017    How to target a transcription factor

The Francois lab discovery that breast cancer in a mouse model can be delayed by pharmacological targeting of the SOX18 transcription factor, published in eLife, was featured on the journal's online cover and was highlighted on the journal's facebook page. This is one of the rare successful examples of targeting a transcription factor with a small compound. This was achieved by a novel molecular strategy that enables us to disrupt multiple protein protein interactions.

Read the eLife article






13 Nov 2014    Experts available to comment on G20 issues

Dr Mat Francois has been named as one of The University of Queensland experts available to comment on issues being discussed by worldwide leaders at the 2014 G20 summit. Dr Francois is investigating key genetic pathways influencing lymphatic vascular development. In adults, abnormal formation of lymphatic vessels is associated with a wide range of diseases that include chronic inflammatory disorders, such as rheumatoid arthritis, cancer metastasis and lymphoedema. Understanding lymphatic development will aid development of new therapies to manage the lymphatic network. Dr Francois also speaks French.
UQ news article


24 May 2013    Cell therapy to fight skin cancer

Mat Francois received funding from the Cancer Council Queensland as one of eight projects at The University of Queensland to be awarded funding. Dr Francois and his team will study the identification of molecules that will enable the manipulation of lymphatic vessel growth with the view to developing new therapeutic avenues for cancer or lymphedema.
UQ news article


13 Sep 2011    UQ researchers celebrated for excellence in their fields

Mat Francois received a UQ Foundation Research Excellence Award for his research identifying and characterising a novel class of molecules that will enable the manipulation of lymphatic vessel growth with a view to developing new therapeutic avenues for cancer or lymphedema. 
UQ news article

18 Nov 2010     Talented UQ health and medical researchers win NHMRC funding

Mat Francois receives the prestigious national Postdoctoral Fellowship to study, Lymphangiogenesis from development to disease: Analysis of SOX18 function in the control of lymphatic remodelling
UQ news article


19 Oct 2008   Knocking the Sox off cancer and lymphatic disorders

Based on Mat Francois and Peter Koopman's discovery of a gene critical for the development of the lymphatic system. Published in Nature, the finding that a single gene - Sox18 - triggers the development of the lymphatic vessels will have implications for treatment of cancer and lymphatic disorders and other diseases.
UQ news article



9 Nov 2015     NHMRC awards more than $11 million to IMB research

Based on Dr Mat Francois' NHMRC funding award, in collaboration with Dr Kelly Smith, to understand how defective copies of specific genes, that are required for the heart to correctly assemble and function, result in cardiovascular disease (CVD). This research will lead to better diagnosis and treatment for CVD, the leading cause of death in Australia.
IMB news article


19 Oct 2012     IMB researchers awarded $12.8M in funding from NHMRC

Based on NHMRC funding awarded to Dr Mat Francois, part of the $12.8 million awarded to IMB scientists for health and medical research in 2013.
IMB news article


28 Oct 2010     Million-dollar funding for IMB research
Based on Mat Francois and Ben Hogan's $340,000 funding grant to study key genes involved in the development of the lymphatic vessel network. Lymphatic vessels play roles in a number of diseases including lymphoedema and cancer. This project will help researchers better understand these diseases.
IMB news article





Francois lab publications



33. Overman J, Fontaine F, Moustaqil M, Mittal D, Sierecki E, Sacilotto N, Zuegg J, Robertson AA, Holmes K, Salim AA, Mamidyala S, Butler MS, Robinson AS, Lesieur E, Johnston W, Alexandrov K, Black BL, Hogan BM, De Val S, Capon RJ, Carroll JS, Bailey TL, Koopman P, Jauch R, Smyth MJ, Cooper MA, Gambin Y, Francois M. Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. eLife 2017; 6:e21221. CCVB News Article

32. Fontaine F, Overman J, Moustaqil M, Mamidyala S, Salim A, Narasimhan K, Prokoph N, Robertson AA, Lua L, Alexandrov K, Koopman P, Capon RJ, Sierecki E, Gambin Y, Jauch R, Cooper MA, Zuegg J, Francois M. Small-Molecule Inhibitors of the SOX18 Transcription Factor. Cell Chemical Biology 2017 Mar 16;24(3):346-359. Pubmed

31. Moon H, Ruelcke J, Choi E, Sharpe L, Nassar Z, Bielefeldt-Ohmann H, Parat MO, Shah A, Francois M, Inder K, Brown A, Russell P, Parton R and Hill M. Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1. Oncotarget. 2015 Apr 10;6(10):7438-53.

30. Aspelund A, Tammela T, Antila S, Nurmi H, Leppanen V-M, Zrakada G, Stanczuk L, Francois M, Makinen T, Saharinen P, Immonen I, Alitalo K. The Schlemm’s canal is a VEGF-C/VEGF-R3-responsive lymphatic-like vessel. J Clin Invest. 2014 Sep;124(9):3975-86.

29. Moalem S, Brouillard P, Kuypers D, Legius E, Harvey E, Taylor G, Francois M, Vikkula M and Chitayat D. Hypotrichosis-Lymphedema-Telangiectasia-Renal defect associated with a truncating mutation in the SOX18 gene. Clin Genet. 2015 Apr;87(4):378-82.

28. Coxam B, Sabine A, Bower NI, Smith KA, Pichol-Thievend C, Skoczylas R, Astin JW, Frampton E, Jaquet M, Crosier PS, Parton RG, Harvey NL, Petrova TV, Schulte-Merker S, Francois M, Hogan BM. Pkd1 regulates lymphatic vascular morphogenesis during development. Cell Reports. 2014. 2014 May 8; 7(3):623-33.

27. Bowles J, Secker G, Nguyen C, Kazenwadel J, Truong V, Frampton E, Curtis C, Skozcylas R, Davidson TL, Miura N, Hong YK, Koopman P, Harvey N, Francois M. (2014) Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo. Dev Biol. 2014 Feb 1;386(1):25-33.

26. Duong T, Koltowska K, Pichol-Thievend C, Le Guen L, Fontaine F, Smith KA, Truong V, Skoczylas R, Stacker SA, Achen MG, Koopman P, Hogan BM*, Francois M* VEGFD regulates blood vascular development by modulating SOX18 activity.  Blood. 2014 Feb; 123(7):1102-12. (*Equal last author) Journal Cover Art

25. Kartopawiro J, Bower NI, Karnezis T, Kazenwadel J, Betterman KL, Lesieur E, Koltowska K, Astin J, Crosier P, Vermeren S, Achen MG, Stacker SA, Smith KA, Harvey NL, Francois M, Hogan BM. Arap3 is dysregulated in a mouse model of hypotrichosis- lymphedema-telangiectasia and regulates lymphatic vascular development. Human Molecular Genetics 2014 Mar 1; 23(5):1286-97.

24. Nassar Z.D., Moon H, Duong T, Neo T, Hill M.M, Francois M, Parton RG, Parat M.O. PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis. Oncotarget 2013 Oct; 4 (10): 1844-55.

23. Cermenati S, Moleri S, Neyt C, Bresciani E, Carra S, Grassini DR, Omini A, Goi M, Cotelli F, François M, Hogan BM, Beltrame M.  Sox18 Genetically Interacts With VegfC to Regulate Lymphangiogenesis in Zebrafish. Arterioscler Thromb Vasc Biol. 2013 Jun; 33(6):1238-47.

22. Oomen S, Francois M, Porntaveetus T, Ghafoor S, Young N, Kawasaki K, Kawasaki M, Okamasu Y, McGrath J, Koopman P, Sharpe P and Ohazama A. Cytoplasmic plaque formation in hemi-desmosome is dependent on SOX18 function. Plos One 2012; 7(9):e43857.

21. Svingen T, Francois M, Wilhelm D and Koopman P. Three-dimensional imaging of Prox1-EGFP transgenic mouse gonads reveals divergent modes of lymphangiogenesis in the testis and ovary. Plos One 2012; 7(12):252620.

20. Duong T, Proulx S, Luciani P, Leroux JC, Detmar M, Koopman P and  Francois M. Genetic ablation of SOX18 function suppresses neo-lymphangiogenesis and tumour metastasis in a mouse model of melanoma. Cancer Research 2012 June15;72(12):3105-14.

19. Newman B, Lose F, Kedda MA, Francois M, Ferguson K, Janda M, Yates P,  Spurdle A.B, Hayes S. C. Possible genetic predisposition to lymphedema after breast cancer. Lymphatic Research Biology 2012 Mar;10(1):2-13.

18. Francois M & Ramchandran R. Studies on Axenfeld-Rieger syndrome patients and mice reveal Foxc1’s role in corneal neovascularisation Invited commentary, PNAS 2012 Feb 7;109(6):1818-9.

17. Francois M, Short K, G Secker, Schwarz Q, Smyth I, Hong Y, Harvey N, Koopman P. Segmental territories along the cardinal veins generate lymph sacs via ballooning mechanism during embryonic lymphangiogenesis in mice. Dev Biol 2012 Apr 15;364(2):89-98.

16. Samant G, Schupp M, François M, Moleri, M, Kothinti R, Zoon Chun C, Sinha I, Sellars S, Leigh N, Pramanik K, Horswill M, Remadevi I, Li K, Wilkinson G, Tabatabai N, Beltrame M, Koopman P, and Ramchandran R. Sox factors transcriptionally regulate robo4 expression in developing vasculature in vivo. J Biol Chem 2011 Sep 2;286(35):30740-7.

15. Francois M, Koopman P, Beltrame M. F-group Sox key modulators in the development of the cardio-vascular system. Invited review for The Int J Biochem Cell Biol 2010 Mar; 42 (3):445-8.

14. Hosking B, Francois M*, Wilhelm D, Orsenigo F, Caprini A, Svingen T, Tutt D, Davidson T, Browne C, Dejana E, Koopman P. Sox7 and Sox17 are strain specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice. Development 2009 July 1; 136(14):2385-91. *co-first author

13. Downes M, Francois M, Fergusson C, Parton RG, Koopman P. Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation. Hum Mol Genet 2009 Aug 1; 18 (15):2839-50.

12. Francois, M. SOX18 orchestrates development of the lymphatic vessels. Med Sci (Paris) 2009; 25:127-9.

11. François M, Caprini A, Hosking B, Orsenigo F, Wilhelm D, Browne C, Paavonen K, Karnezis K, Shayan R, Downes M, Davidson T, Tutt D, Cheah K, Lau M, Stacker SA, Muscat G, Achen M, Dejana E and Koopman P. SOX18 initiates lymphatic development in mice by direct activation of Prox1 expression. Nature 2008; 456:643-7.

10. Richette P, François M, Vicaut E, Fitting C, Bardin T, Corvol M, Savouret JF, Rannou F.  A high interleukin 1 receptor antagonist/IL-1beta ratio occurs naturally in knee osteoarthritis. J Rheumatol 2008 Aug; 35(8): 1650-4.

9. Benallaoua M, Francois M, Batteux F, Shyy J, Fitting C, Tsagris L, Boczkowski J, Savouret J-F, Corvol MT, Poiraudeau S, and Rannou F. Pharmacological Induction of Heme Oxygenase-1 Decreases the Acute Phase of Inflammatory Arthritis. Arthritis Rheum 2007; 56:2585-94.

8. Benallaoua, M, Richette, P, François, M, Tsagris, L, Revel, M, Corvol, M, Poiraudeau, S, Savouret, JF and Rannou, F. Modulation of proteoglycan production by cyclic tensile stretch in intervertebral disc cells through a post-translational mechanism. Biorheol 2006; 43:303–310.

7. François, M, Richette, P, Tsagris, L, Fitting, C, Lemay, C, Benallaoua, M, Tahiri, K and Corvol MT. Activation of the peroxisome proliferator-activated receptor alpha pathway potentiates interleukin-1 receptor antagonist production in cytokine-treated chondrocytes. Arthritis Rheum 2006; 54:1233–1245.

6. Moulin, D, Bianchi, A, Boyault, S, Morin, S, Koufany, M, François, M, Netter, P, Jouzeau J-Y and Terlain, B. Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1 beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism. Arthritis Rheum 2005; 52:759–769.

5. Boyault, S, Bianchi, A, Moulin, D, Morin, S, François, M, Netter, P, Terlain B and Bordji, K. Anti inflammatory effect of 15-deoxy-D12,14-prostaglandine j2 is peroxisome proliferator-activated receptor gamma independent in interleukine-1ß-treated rat chondrocytes: Identification of intra-cellular targets. FEBS Lett 2004; 572:33–40.

4. François, M, Richette, P, Tsagris, L, Raymondjean, M, Fulchignoni-Lataud, MC, Savouret, JF, Forest, C and Corvol MT. PPAR-gamma down-regulates chondrocytes matrix metallo-proteinase-1 via a novel composite element. J Biol Chem 2004; 279: 28411–28418.

3. Richette, P, Dumontier, MF, François, M, Tsagris, L, Korwin, ZC, Rannou, F and Corvol, MT. Dual effect of 17β-oestradiol on interleukin-1ß-induced proteoglycan degradation in chondrocytes. Ann Rheum Dis 2004; 63:191-9.

2. Rannou, F, Richette, P, Benallaoua, M, François, M, Genries, V, Korwin-Zmijowska, C, Revel, M, Corvol, M and Poiraudeau S. Cyclic tensile stretch modulates proteoglycan production by intervertebral disc annulus fibrosus cells through production of nitrite oxide. J Cell Biochem 2003; 90:148–157.

1. Francois M, Le Cabec V, Dupont MA, Sansonetti PJ, Maridonneau-Parini I. Induction of necrosis in human neutrophils by Shigella Flexneri requires type III secretion, IpaB and IpaC invasins, and actin polymerization. Infect Immun 2000; 68:1289-96.



8. Fontaine F, Overman J and Francois M. Pharmacological manipulation of transcription factors activity: opportunities and obstacles. Cell Regen (Lond). 2015 Mar 12;4(1):2.

7. Pichol-Thievend C, Hogan BM, Francois M. Lymphatic vascular specification and its modulation during embryonic development. Microvascular Research. 2014 Nov; 96:3-9. (Special Issue: Lymphatics in Development and Pathology) Review

6. Francois M, Shayan R, Karnezis T. Ordered Chaos: Harnessing Developmental Pathways in Tumor-Induced Lymphangiogenesis. J Clin Cell Immunol 2014; 5:270. doi: 10.4172/2155-9899.1000270. Review

5. Overman J and Francois M. Transcriptional modulation of tumour induced angiogenesis. Research Directions in Tumour Angiogenesis. 2013 Feb; Chapter 1. DOI: 10.5772/54055. Book Chapter

4. Duong T, P Koopman, Francois M. Tumour lymphangiogenesis as a potential therapeutic target. J Oncol 2012; 2012:204946. Special Issue Tumour Angiogenesis. Invited Review

3. Francois M*, Harvey NL, Hogan BM. The transcriptional control of lymphatic vascular development. Physiology 2011 Jun; 26(3):146-55. *Corresponding author. Review

2. Rannou, F, François, M, Corvol, MT and Berenbaum, F. Cartilage breakdown in rheumatoid arthritis. J Bone Spine 2006; 73:29–36. Review

1. François M, Richette P, Corvol MT. Peroxisome proliferator-activated receptor gamma and its ligands in controlling interleukin-1 beta target gene expression: a confusing story. Drug News Perspect 2005; 18:257–261. Review