Genomes and Genes
Affiliation: University of Melbourne
- Lappas M, Mitton A, Mittion A, Permezel M. In response to oxidative stress, the expression of inflammatory cytokines and antioxidant enzymes are impaired in placenta, but not adipose tissue, of women with gestational diabetes. J Endocrinol. 2010;204:75-84 pubmed publisher..This may represent a protective or adaptive mechanism to prevent damage from further oxidative insult in utero as indicated by increased tissue antioxidant expression. ..
- Lim R, Lappas M. A novel role for GSK3 in the regulation of the processes of human labour. Reproduction. 2015;149:189-202 pubmed publisher..Pharmacological blockade of the kinase GSK3 markedly reduced pro-inflammatory and pro-labour mediators in human foetal membranes and myometrium, providing a possible therapeutics for the management of preterm labour. ..
- Willcox J, Campbell K, McCarthy E, Wilkinson S, Lappas M, Ball K, et al. Testing the feasibility of a mobile technology intervention promoting healthy gestational weight gain in pregnant women (txt4two) - study protocol for a randomised controlled trial. Trials. 2015;16:209 pubmed publisher..Australian New Zealand Clinical Trials Registry: ACTRNU111111544397 . Date of registration: 19 March 2014. ..
- Brickle A, Tran H, Lim R, Liong S, Lappas M. Autophagy, which is decreased in labouring fetal membranes, regulates IL-1Î² production via the inflammasome. Placenta. 2015;36:1393-404 pubmed publisher..IL-1Î² is a major contributor to the pathophysiology of spontaneous preterm birth. Therefore activation of autophagy may be a potential therapeutic mechanism to delay or prevent infection-induced preterm birth. ..
- Lappas M, Lim R, Riley C, Menon R, Permezel M. Expression and localisation of FoxO3 and FoxO4 in human placenta and fetal membranes. Placenta. 2010;31:1043-50 pubmed publisher..Presence of FoxO3 and FoxO4 are expected to contribute to apoptosis and/or cell cycle regulation associated with fetal membrane rupture. ..
- Lappas M, Permezel M, Georgiou H, Rice G. Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod. 2002;67:668-73 pubmed..The control of NF-kappaB activation may therefore provide an alternative therapeutic strategy for reducing the release of proinflammatory mediators in infection associated preterm labor. ..
- Willcox J, Campbell K, McCarthy E, Lappas M, Ball K, Crawford D, et al. Gestational weight gain information: seeking and sources among pregnant women. BMC Pregnancy Childbirth. 2015;15:164 pubmed publisher..The small numbers given GWG targets, and the dominance of non-clinical information sources, reinforces that an important opportunity to provide evidence based advice and guidance in the antenatal care setting is currently being missed. ..
- Lappas M. Nuclear factor-?B mediates placental growth factor induced pro-labour mediators in human placenta. Mol Hum Reprod. 2012;18:354-61 pubmed publisher..The PLGF-induced pro-labour responses were abrogated by co-treatment with the NF-?B inhibitor BAY 11-7082. In summary, the pro-inflammatory and pro-labour effects of PLGF in human placenta are mediated by NF-?B. ..
- Lappas M, Mundra P, Wong G, Huynh K, Jinks D, Georgiou H, et al. The prediction of type 2 diabetes in women with previous gestational diabetes mellitus using lipidomics. Diabetologia. 2015;58:1436-42 pubmed publisher..This report is the first to use plasma lipidomic analysis to identify individual lipids as potential biomarkers for the prediction of type 2 diabetes in women with a history of GDM. ..
- Lappas M. Double stranded viral RNA induces inflammation and insulin resistance in skeletal muscle from pregnant women in vitro. Metabolism. 2015;64:642-53 pubmed publisher..It should be noted that the in vitro studies cannot be directly used to infer the same outcomes in the intact subject. ..
- Seth S, Lewis A, Saffery R, Lappas M, Galbally M. Maternal Prenatal Mental Health and Placental 11Î²-HSD2 Gene Expression: Initial Findings from the Mercy Pregnancy and Emotional Wellbeing Study. Int J Mol Sci. 2015;16:27482-96 pubmed publisher..These findings suggest that maternal depression and anxiety may impact on fetal programming by down-regulating HSD11B2, and antidepressant treatment alone is unlikely to protect against this effect. ..
- Lappas M, Rice G. Transcriptional regulation of the processes of human labour and delivery. Placenta. 2009;30 Suppl A:S90-5 pubmed publisher..We also propose that coordination of these different pathways is achieved by competition for common cofactors that control the activity of NRs in human gestational tissues. ..
- Liong S, Lappas M. Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women. J Physiol Biochem. 2015;71:703-17 pubmed publisher..These findings suggest that AMPK may play an important role in inflammation and insulin resistance. ..
- Lappas M, Permezel M, Georgiou H, Rice G. Regulation of phospholipase isozymes by nuclear factor-kappaB in human gestational tissues in vitro. J Clin Endocrinol Metab. 2004;89:2365-72 pubmed..In addition, SASP concentrations of 5 mM or greater significantly suppressed NF-kappaB DNA binding activity. These data are consistent with the hypothesis that NF-kappaB regulates the expression and release of phospholipase isozymes. ..
- Lappas M. KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium. Reproduction. 2015;149:413-24 pubmed publisher..In conclusion, this study describes novel data in which KLF5 is increased in labouring myometrium, and KLF5 silencing decreased inflammation- and infection-induced pro-labour mediators. ..
- Lim R, Barker G, Lappas M. Human cathelicidin antimicrobial protein 18 (hCAP18/LL-37) is increased in foetal membranes and myometrium after spontaneous labour and delivery. J Reprod Immunol. 2015;107:31-42 pubmed publisher..LL-37 also significantly increased NF-ÎºB transcriptional activity. In conclusion, hCAP18/LL-37 induces pro-inflammatory and pro-labour mediators, via the MyD88/NF-ÎºB pathway. ..
- Lappas M, Yee K, Permezel M, Rice G. Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells. Placenta. 2006;27:568-75 pubmed
- Liong S, Barker G, Lappas M. Placental Pim-1 expression is increased in obesity and regulates cytokine- and toll-like receptor-mediated inflammation. Placenta. 2017;53:101-112 pubmed publisher..The findings from this study implicate Pim-1 may contribute to placental inflammation in pregnancies complicated by maternal obesity. Thus, therapeutic targets for Pim-1 may improve fetal outcomes complicated by obese pregnancies. ..
- Lim R, Barker G, Lappas M. PARK7 regulates inflammation-induced pro-labour mediators in myometrial and amnion cells. Reproduction. 2018;155:207-218 pubmed publisher..Collectively, our novel data describe a role for PARK7 in regulating inflammation-induced pro-inflammatory and pro-labour mediators in human myometrial and amnion cells. ..
- Lappas M. Activation of inflammasomes in adipose tissue of women with gestational diabetes. Mol Cell Endocrinol. 2014;382:74-83 pubmed publisher..In conclusion, the present findings describe an important role for adipose tissue inflammasome activation in the development of insulin resistance associated in pregnancies complicated by GDM. ..
- Lappas M. RKIP is decreased in laboring myometrium and modulates inflammation-induced pro-labor mediators. Reproduction. 2017;153:545-553 pubmed publisher..In conclusion, in human primary myometrial cells, RKIP negatively regulates IL1B- and TNF-induced expression and or secretion of pro-inflammatory and pro-labor mediators by inhibiting NF-ÎºB RELA activation. ..
- Lappas M. Lower circulating levels of complement split proteins C3a and C4a in maternal plasma of women with gestational diabetes mellitus. Diabet Med. 2011;28:906-11 pubmed publisher..Gestational diabetes is characterized by lower levels of C3a and C4a in the maternal circulation at the time of term Caesarean delivery. ..
- Liong S, Lappas M. Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women. Mol Cell Endocrinol. 2016;425:11-25 pubmed publisher..In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. ..
- Lappas M. RAF1 is increased in labouring myometrium and modulates inflammation-induced pro-labour mediators. Reproduction. 2016;151:411-20 pubmed publisher..TNF, on the other hand, regulates pro-labour mediators through the RAF1-NF-ÎºB signalling pathway via an MAPK1-independent mechanism. ..
- Lappas M. Runt-related transcription factor 1 (RUNX1) deficiency attenuates inflammation-induced pro-inflammatory and pro-labour mediators in myometrium. Mol Cell Endocrinol. 2018;473:61-71 pubmed publisher..Targeting RUNX1 may be a novel approach to prevent preterm labor. ..
- Liong S, Lappas M. Lipopolysaccharide and double stranded viral RNA mediate insulin resistance and increase system a amino acid transport in human trophoblast cells in vitro. Placenta. 2017;51:18-27 pubmed publisher..This suggests that the presence of low-grade maternal infection can contribute to excess placental nutrient availability and promote fetal overgrowth in pregnancies complicated by GDM and/or obesity. ..
- Lim R, Barker G, Liong S, Nguyen Ngo C, Tong S, Kaitu u Lino T, et al. ATF3 is a negative regulator of inflammation in human fetal membranes. Placenta. 2016;47:63-72 pubmed publisher..Our data suggest that ATF3 may play a role in the terminal processes of human labour and delivery. ..
- Lim R, Barker G, Menon R, Lappas M. A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery. Biol Reprod. 2016;95:95 pubmed..In human myometrium, SIRT3 expression decreases with term labor and regulates the mediators involved in the terminal effector pathways of human labor and delivery through the NFkappaB1 pathway. ..
- Lappas M, Jinks D, Shub A, Willcox J, Georgiou H, Permezel M. Postpartum IGF-I and IGFBP-2 levels are prospectively associated with the development of type 2 diabetes in women with previous gestational diabetes mellitus. Diabetes Metab. 2016;42:442-447 pubmed publisher..This is the first report that identifies IGF-I and IGFBP-2 as a potential biomarker for the prediction of type 2 diabetes in women with a history of GDM. ..
- Lappas M, Yee K, Permezel M, Rice G. Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology. 2005;146:1491-7 pubmed..Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus. ..
- Lim R, Barker G, Lappas M. TLR2, TLR3 and TLR5 regulation of pro-inflammatory and pro-labour mediators in human primary myometrial cells. J Reprod Immunol. 2017;122:28-36 pubmed publisher..Our study signifies that these adaptor molecules are necessary for the proper production of cytokines, chemokines and pro-labour mediators after TLR ligation. ..
- Lappas M, Lim R, Riley C, Rice G, Permezel M. Localisation and expression of FoxO1 proteins in human gestational tissues. Placenta. 2009;30:256-62 pubmed publisher..The exact role of FoxO1 proteins in human pregnancy are unknown, however the finding that they are expressed in human gestational tissues warrants further research into their function in these tissues. ..
- Lappas M, Mitton A, Lim R, Barker G, Riley C, Permezel M. SIRT1 is a novel regulator of key pathways of human labor. Biol Reprod. 2011;84:167-78 pubmed publisher..In conclusion, SIRT1 possesses anti-inflammatory actions and thus may play a role in regulating pregnancy and parturition. ..
- Lappas M. Copper metabolism domain-containing 1 represses the mediators involved in the terminal effector pathways of human labour and delivery. Mol Hum Reprod. 2016;22:299-310 pubmed publisher..1047025). Additional funding was provided by the Medical Research Foundation for Women and Babies and the Mercy Research Foundation. The author has no conflict of interest. ..
- Lappas M, Andrikopoulos S, Permezel M. Hypoxanthine-xanthine oxidase down-regulates GLUT1 transcription via SIRT1 resulting in decreased glucose uptake in human placenta. J Endocrinol. 2012;213:49-57 pubmed publisher..Collectively, the data presented here demonstrate that oxidative stress reduces placental glucose uptake and GLUT1 expression by a SIRT1-dependent mechanism. ..
- Lappas M, Woodruff T, Taylor S, Permezel M. Complement C5A regulates prolabor mediators in human placenta. Biol Reprod. 2012;86:190 pubmed publisher..We conclude that C5a upregulates prolabor mediators in human gestational tissues via CD88-mediated NFKB activation. ..
- Lappas M. Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells. Mediators Inflamm. 2012;2012:597514 pubmed publisher..SIRT6 may be a potential pharmacological target for inflammatory vascular diseases. ..
- Lappas M. Markers of endothelial cell dysfunction are increased in human omental adipose tissue from women with pre-existing maternal obesity and gestational diabetes. Metabolism. 2014;63:860-73 pubmed publisher..To determine the effect of maternal obesity and gestational diabetes mellitus (GDM) on the expression and release of genes involved in endothelial cell dysfunction in human placenta and omental adipose tissue...
- Lappas M. NOD1 expression is increased in the adipose tissue of women with gestational diabetes. J Endocrinol. 2014;222:99-112 pubmed publisher..In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM. ..
- Lappas M, Permezel M, Rice G. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated ki. Endocrinology. 2005;146:3334-42 pubmed
- Makino S, Zaragoza D, Mitchell B, Yonemoto H, Olson D. Decidual activation: abundance and localization of prostaglandin F2alpha receptor (FP) mRNA and protein and uterine activation proteins in human decidua at preterm birth and term birth. Placenta. 2007;28:557-65 pubmed..These results suggest that the induction of Prostaglandin F(2alpha) receptor at term may facilitate the decidua contribution to parturition, and its regulation and role should be examined further. ..
- Lappas M, Odumetse T, Riley C, Reti N, Holdsworth Carson S, Rice G, et al. Pre-labour fetal membranes overlying the cervix display alterations in inflammation and NF-kappaB signalling pathways. Placenta. 2008;29:995-1002 pubmed publisher..In summary, data from this study confirm that supracervical fetal membranes display altered structural and biochemical characteristics. ..
- Lappas M. Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue. Metabolism. 2014;63:250-62 pubmed publisher..To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism...
- Lappas M. The IL-1? signalling pathway and its role in regulating pro-inflammatory and pro-labour mediators in human primary myometrial cells. Reprod Biol. 2017;17:333-340 pubmed publisher..Collectively, these findings suggest that MyD88, TRAF6, IRAK4 and TAK1 are involved in IL-1? signalling in human myometrium. Further studies are required to determine if inhibition of these proteins can prevent preterm birth. ..
- Lappas M. NOD1 and NOD2 regulate proinflammatory and prolabor mediators in human fetal membranes and myometrium via nuclear factor-kappa B. Biol Reprod. 2013;89:14 pubmed publisher..NOD1 and NOD2 may thus represent therapeutic targets for the treatment and/or management of preterm birth. ..
- Murthi P, Sarkis R, Lim R, Nguyen Ngo C, Pratt A, Liong S, et al. Endocan expression is increased in the placenta from obese women with gestational diabetes mellitus. Placenta. 2016;48:38-48 pubmed publisher..Further studies are required to elucidate the functional consequences of increased placental endocan expression in obese GDM pregnancies. ..
- Lappas M, Riley C, Lim R, Barker G, Rice G, Menon R, et al. MAPK and AP-1 proteins are increased in term pre-labour fetal membranes overlying the cervix: regulation of enzymes involved in the degradation of fetal membranes. Placenta. 2011;32:1016-25 pubmed publisher..Thus, the MAPK/AP-1 pathway may play a role in the degradation of the ECM at the SCS making it more susceptible to membrane rupture. ..
- Lim R, Barker G, Lappas M. Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators. Placenta. 2015;36:454-62 pubmed publisher..The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. ..