Skip to main content

Bill Kalionis

University of Melbourne, Obstetrics and Gynaecology, Adjunct

Followers

49

Following

21

Co-authors

21

Public Views

The University of Western Australia

Monash University

Michigan State University

UPJV, Amiens

Kathie Berghorn

Monash University

Interests

Uploads

Papers by Bill Kalionis

Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta

by Padma Murthi and Bill Kalionis

Placenta, 2010

a b s t r a c t DLX3, a member of the large homeobox gene family of transcription factors, is nec... more a b s t r a c t DLX3, a member of the large homeobox gene family of transcription factors, is necessary for normal placentation. Targeted deletion of dlx3 in mouse resulted in embryonic death due to placental failure. This study demonstrates the presence of DLX3 mRNA expression in human first trimester and term placental tissue, cultured trophoblast-like cell lines and in isolated primary villous and extravillous trophoblast cells. Using an ovine polyclonal antibody, the spatial distribution was identified for DLX3 in human placental tissues, trophoblast cell lines and in freshly isolated primary trophoblast cells. A 50 kDa immunoreactive DLX3 protein was detected in the human placenta, in trophoblast cell lines and in primary trophoblast cells. Nuclear expression for DLX3 was observed in villous cytotrophoblasts, syncytiotrophoblast and extravillous cytotrophoblast in the proximal regions of the cytotrophoblast cell columns in first trimester placental tissues. Immunoreactivity was also detected in few stromal cells and microvascular endothelial cells surrounding the fetal capillaries. In the first trimester placental bed, DLX3 expression was predominantly observed in the cytoplasm of the endovascular and interstitial trophoblasts. We conclude that the cellular expression of DLX3 was extensive in the human placenta and propose that DLX3 may play an important role in normal placental development.

Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression

by Padma Murthi, Gillian Barker, Mark Baker, and Bill Kalionis

Gynecologic Oncology, 2004

Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety o... more Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.

P106 Placental mesenchymal stem cells functional abnormally and show gene expression changes in preeclampsia

by Rishika Pace and Bill Kalionis

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2010

cohort. We measured maternal first trimester total 25(OH)D by LC-MS/MS and VDBP by ELISA, then ca... more cohort. We measured maternal first trimester total 25(OH)D by LC-MS/MS and VDBP by ELISA, then calculated free 25(OH)D levels in pregnancies complicated by subsequent PE, GDM, and SGA and compared them to levels in uncomplicated pregnancy. Results: 25(OH)D Levels were similar in subjects with normal pregnancies (28.8±0.80 ng/ml), subjects who developed preeclampsia (27.4±1.9 ng/ml, p=0.44), and subjects who gave birth to SGA infants (27.8±1.6 ng/ml, p=0.54). Women who developed GDM had lower first trimester 25(OH)D levels (25.1±1.9, p= 0.02), but not after adjustment for body mass index. Among all subjects, 25(OH)D and DBP levels were correlated (r=0.294, p<0.001) First trimester VDBP levels and free 25(OH)D were similar across groups in univariate and multivariate analyses. Free 25(OH)D levels were not associated with body mass index or race. Conclusions: First trimester total and free 25(OH)D levels are not independently associated with subsequent preeclampsia, gestational diabetes mellitus, or small for gestational age birth weight.

The Homeobox Genes MSX2 and MOX2 are Candidates for Regulating Epithelial–Mesenchymal Cell Interactions in the Human Placenta

Placenta, 2000

Homeobox genes of the Msx and Mox families are coexpressed in the vertebrate embryo in regions of... more Homeobox genes of the Msx and Mox families are coexpressed in the vertebrate embryo in regions of epithelial–mesenchymal interactions. Here we show that a member of each family is expressed in extra-embryonic structures where epithelial and mesenchymal cell layers contact. In situ hybridization studies on first trimester human placental sections reveal that MSX2 and MOX2 are expressed predominantly in the

Gene Isolation by Screening λgt11 Expression Libraries with DNA-Binding Site Probes

In Vitro Transcription and Translation Protocols, 1995

ABSTRACT

Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5

Stem cells international, 2015

Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and olig... more Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2'-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. Immunofluorescence analysis showed OA significantly elevated...

NIH Public Access

Mechanisms of Development

Detection of paternally inherited mutations for beta-thalassemia in trophoblast isolated from peripheral maternal blood

Annals of the New York Academy of Sciences

Isolating fetal trophoblast cells for prenatal genetic diagnosis

JAMA The Journal of the American Medical Association

Opposing effects of HGF and TGF-beta on HLX1 expression and trophoblast proliferation

Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins

Molecular and Cellular Biology

We report the identification of a new family of DNA-binding proteins from our characterization of... more We report the identification of a new family of DNA-binding proteins from our characterization of the dead ringer (dri) gene of Drosophila melanogaster. We show that dri encodes a nuclear protein that contains a sequence-specific DNA-binding domain that bears no similarity to known DNA-binding domains. A number of proteins were found to contain sequences homologous to this domain. Other proteins containing the conserved motif include yeast SWI1, two human retinoblastoma binding proteins, and other mammalian regulatory proteins. A mouse B-cell-specific regulator exhibits 75% identity with DRI over the 137-amino-acid DNA-binding domains of these proteins, indicating a high degree of conservation of this domain. Gel retardation and optimal binding site screens revealed that the in vitro sequence specificity of DRI is strikingly similar to that of many homeodomain proteins, although the sequence and predicted secondary structure do not resemble a homeodomain. The early general expression of dri and the similarity of DRI and homeodomain in vitro DNA-binding specificity compound the problem of understanding the in vivo specificity of action of these proteins. Maternally derived dri product is found throughout the embryo until germ band extension, when dri is expressed in a developmentally regulated set of tissues, including salivary gland ducts, parts of the gut, and a subset of neural cells. The discovery of this new, conserved DNA-binding domain offers an explanation for the regulatory activity of several important members of this class and predicts significant regulatory roles for the others.

Altered activin receptor ACVR2A expression in pre-eclampsia contributes to abnormal placentation

Placenta, 2015

significantly increasing trophoblast apoptosis and reducing trophoblast proliferation in vitro. C... more significantly increasing trophoblast apoptosis and reducing trophoblast proliferation in vitro. Conclusion: The finding that dMØs become increasingly immunosuppressive throughout early pregnancy is likely to reflect the requirement for an environment tolerant to the semi-allogeneic fetus to support a successful pregnancy. Alterations in the phenotype of high-RI dMØs when compared with normal-RI dMØs are particularly interesting given that pre-eclampsia is associated with impaired trophoblast invasion and remodelling of uterine spiral arteries during the first trimester, suggesting a role for impaired dMØ-trophoblast interactions.

An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction

Molecular Medicine

Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. ... more Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that EG-VEGF (endocrine gland derived-vascular endothelial growth factor), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesise that EG-VEGF-dependent change in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a Homeobox gene cDNA array on placental explants of 8-12 weeks' gestation after stimulation with EG-VEGF in vitro for 24 hours. The Homeobox gene array identified a >5-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a >2 fold-decrease in mRNA expression compared to untreated controls. Homeobox ge...

Anti-angiogenic collagen fragment arresten is increased from 16 weeks' gestation in pre-eclamptic plasma

Placenta, Jan 29, 2015

Arresten and canstatin are endogenous anti-angiogenic factors derived from type IV collagen α-cha... more Arresten and canstatin are endogenous anti-angiogenic factors derived from type IV collagen α-chains COL4A1 and COL4A2 respectively. While their functions are explored in cancer studies, little is known about their role in pregnancy. Pre-eclampsia (PE) is a common, serious hypertensive disorder of pregnancy that is characterised by systemic endothelial dysfunction. COL4A1 and COL4A2 are maternal PE susceptibility genes that have increased mRNA expression in PE decidua. Our study aim was to determine the levels of arresten and canstatin in plasma and decidua from PE and gestational age matched normotensive patients. Plasma was collected from normotensive (n = 44) and PE (n = 39) women during the second and third trimesters of pregnancy. Third trimester decidua was collected at delivery from normotensive and PE women (n = 4 each). Levels of arresten and canstatin were determined by Western immunoblotting. Arresten levels were significantly increased in second and third trimester PE pl...

Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

Stem cells international, 2015

Neurodegeneration is the umbrella term for the progressive loss of structure or function of neuro... more Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are pe...

A distal-less class homeobox gene, DLX4, is a candidate for regulating epithelial-mesenchymal cell interactions in the human placenta

Placenta

Homeobox genes of the Distal-less (Dlx) family are expressed in the vertebrate embryo in regions ... more Homeobox genes of the Distal-less (Dlx) family are expressed in the vertebrate embryo in regions where epithelial cell layers contact adjacent mesenchymal cells. This study shows that the human Dlx family member, DLX4, is expressed in the placenta, primarily in regions where epithelial and mesenchymal cell layers contact. In situ hybridization studies at first trimester human placental sections revealed that DLX4 was expressed predominantly in the cytotrophoblast stem cell layer. In term placenta, DLX4 was expressed in the syncytiotrophoblast. Northern analysis revealed two DLX4 transcripts in first trimester placenta of 2.8 and 3.0 kb. Elevated levels of DLX4 mRNA were detected in a choriocarcinoma derived cell line when compared with a cytotrophoblast cell line and normal placenta. This is the first study to show that a member of the Dlx family of homeobox genes is expressed in regions of epithelial and mesenchymal cell layer contact in the human. Accumulated evidence from several...

Decidual mesenchymal stem cells have reduced resistance to oxidative stress in preeclampsia, which is restored by the aldehyde dehydrogenase agonist Alda-1

Placenta, 2013

Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes

PloS one, 2015

Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic compone... more Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examin...

Aβ1-42 oligomer-induced leakage in an in vitro blood brain barrier model is associated with upregulation of RAGE and metalloproteinases, and downregulation of tight junction scaffold proteins

Journal of neurochemistry, Jan 11, 2015

Accumulating evidence indicates that abnormal deposition of amyloid-β (Aβ) peptide in the brain i... more Accumulating evidence indicates that abnormal deposition of amyloid-β (Aβ) peptide in the brain is responsible for endothelial cell (EC) damage and consequently leads to blood-brain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Aβ1-42, and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5 and Occludin) were decreased. Through comparisons of the effects of the different components of Aβ1-42 , including monomer (Aβ1-42 -Mono), oligomer (Aβ1-42 -Oligo) and fibril (Aβ1-42 -Fibril), our data confirmed that Aβ1-42 -Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in AD. We found that the incubation of bEnd.3 cells with Aβ1-42 significantly upregulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RA...

Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins

Molecular and cellular biology, 1996

We reported the identification of a new family of DNA-binding proteins from our characterization ... more We reported the identification of a new family of DNA-binding proteins from our characterization of the dead ringer (dri) gene of Drosophila melanogaster. We show that dri encodes a nuclear protein that contains a sequence-specific DNA-binding domain that bears no similarity to known DNA-binding domains. A number of proteins were found to contain sequences homologous to this domain. Other proteins containing the conserved motif include yeast SWI1, two human retinoblastoma binding proteins, and other mammalian regulatory proteins. A mouse B-cell-specific regulator exhibits 75% identity with DRI over the 137-amino-acid DNA-binding domains of these proteins, indicating a high degree of conservation of this domain. Gel retardation and optimal binding site screens revealed that the in vitro sequence specificity of DRI is strikingly similar to that of many homeodomain proteins, although the sequence and predicted secondary structure do not resemble a homeodomain. The early general express...

Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta

by Padma Murthi and Bill Kalionis

Placenta, 2010

a b s t r a c t DLX3, a member of the large homeobox gene family of transcription factors, is nec... more a b s t r a c t DLX3, a member of the large homeobox gene family of transcription factors, is necessary for normal placentation. Targeted deletion of dlx3 in mouse resulted in embryonic death due to placental failure. This study demonstrates the presence of DLX3 mRNA expression in human first trimester and term placental tissue, cultured trophoblast-like cell lines and in isolated primary villous and extravillous trophoblast cells. Using an ovine polyclonal antibody, the spatial distribution was identified for DLX3 in human placental tissues, trophoblast cell lines and in freshly isolated primary trophoblast cells. A 50 kDa immunoreactive DLX3 protein was detected in the human placenta, in trophoblast cell lines and in primary trophoblast cells. Nuclear expression for DLX3 was observed in villous cytotrophoblasts, syncytiotrophoblast and extravillous cytotrophoblast in the proximal regions of the cytotrophoblast cell columns in first trimester placental tissues. Immunoreactivity was also detected in few stromal cells and microvascular endothelial cells surrounding the fetal capillaries. In the first trimester placental bed, DLX3 expression was predominantly observed in the cytoplasm of the endovascular and interstitial trophoblasts. We conclude that the cellular expression of DLX3 was extensive in the human placenta and propose that DLX3 may play an important role in normal placental development.

Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression

by Padma Murthi, Gillian Barker, Mark Baker, and Bill Kalionis

Gynecologic Oncology, 2004

Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety o... more Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.

P106 Placental mesenchymal stem cells functional abnormally and show gene expression changes in preeclampsia

by Rishika Pace and Bill Kalionis

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2010

cohort. We measured maternal first trimester total 25(OH)D by LC-MS/MS and VDBP by ELISA, then ca... more cohort. We measured maternal first trimester total 25(OH)D by LC-MS/MS and VDBP by ELISA, then calculated free 25(OH)D levels in pregnancies complicated by subsequent PE, GDM, and SGA and compared them to levels in uncomplicated pregnancy. Results: 25(OH)D Levels were similar in subjects with normal pregnancies (28.8±0.80 ng/ml), subjects who developed preeclampsia (27.4±1.9 ng/ml, p=0.44), and subjects who gave birth to SGA infants (27.8±1.6 ng/ml, p=0.54). Women who developed GDM had lower first trimester 25(OH)D levels (25.1±1.9, p= 0.02), but not after adjustment for body mass index. Among all subjects, 25(OH)D and DBP levels were correlated (r=0.294, p<0.001) First trimester VDBP levels and free 25(OH)D were similar across groups in univariate and multivariate analyses. Free 25(OH)D levels were not associated with body mass index or race. Conclusions: First trimester total and free 25(OH)D levels are not independently associated with subsequent preeclampsia, gestational diabetes mellitus, or small for gestational age birth weight.

The Homeobox Genes MSX2 and MOX2 are Candidates for Regulating Epithelial–Mesenchymal Cell Interactions in the Human Placenta

Placenta, 2000

Homeobox genes of the Msx and Mox families are coexpressed in the vertebrate embryo in regions of... more Homeobox genes of the Msx and Mox families are coexpressed in the vertebrate embryo in regions of epithelial–mesenchymal interactions. Here we show that a member of each family is expressed in extra-embryonic structures where epithelial and mesenchymal cell layers contact. In situ hybridization studies on first trimester human placental sections reveal that MSX2 and MOX2 are expressed predominantly in the

Gene Isolation by Screening λgt11 Expression Libraries with DNA-Binding Site Probes

In Vitro Transcription and Translation Protocols, 1995

ABSTRACT

Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5

Stem cells international, 2015

Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and olig... more Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2'-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. Immunofluorescence analysis showed OA significantly elevated...

NIH Public Access

Mechanisms of Development

Detection of paternally inherited mutations for beta-thalassemia in trophoblast isolated from peripheral maternal blood

Annals of the New York Academy of Sciences

Isolating fetal trophoblast cells for prenatal genetic diagnosis

JAMA The Journal of the American Medical Association

Opposing effects of HGF and TGF-beta on HLX1 expression and trophoblast proliferation

Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins

Molecular and Cellular Biology

We report the identification of a new family of DNA-binding proteins from our characterization of... more We report the identification of a new family of DNA-binding proteins from our characterization of the dead ringer (dri) gene of Drosophila melanogaster. We show that dri encodes a nuclear protein that contains a sequence-specific DNA-binding domain that bears no similarity to known DNA-binding domains. A number of proteins were found to contain sequences homologous to this domain. Other proteins containing the conserved motif include yeast SWI1, two human retinoblastoma binding proteins, and other mammalian regulatory proteins. A mouse B-cell-specific regulator exhibits 75% identity with DRI over the 137-amino-acid DNA-binding domains of these proteins, indicating a high degree of conservation of this domain. Gel retardation and optimal binding site screens revealed that the in vitro sequence specificity of DRI is strikingly similar to that of many homeodomain proteins, although the sequence and predicted secondary structure do not resemble a homeodomain. The early general expression of dri and the similarity of DRI and homeodomain in vitro DNA-binding specificity compound the problem of understanding the in vivo specificity of action of these proteins. Maternally derived dri product is found throughout the embryo until germ band extension, when dri is expressed in a developmentally regulated set of tissues, including salivary gland ducts, parts of the gut, and a subset of neural cells. The discovery of this new, conserved DNA-binding domain offers an explanation for the regulatory activity of several important members of this class and predicts significant regulatory roles for the others.

Altered activin receptor ACVR2A expression in pre-eclampsia contributes to abnormal placentation

Placenta, 2015

significantly increasing trophoblast apoptosis and reducing trophoblast proliferation in vitro. C... more significantly increasing trophoblast apoptosis and reducing trophoblast proliferation in vitro. Conclusion: The finding that dMØs become increasingly immunosuppressive throughout early pregnancy is likely to reflect the requirement for an environment tolerant to the semi-allogeneic fetus to support a successful pregnancy. Alterations in the phenotype of high-RI dMØs when compared with normal-RI dMØs are particularly interesting given that pre-eclampsia is associated with impaired trophoblast invasion and remodelling of uterine spiral arteries during the first trimester, suggesting a role for impaired dMØ-trophoblast interactions.

An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction

Molecular Medicine

Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. ... more Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that EG-VEGF (endocrine gland derived-vascular endothelial growth factor), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesise that EG-VEGF-dependent change in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a Homeobox gene cDNA array on placental explants of 8-12 weeks' gestation after stimulation with EG-VEGF in vitro for 24 hours. The Homeobox gene array identified a >5-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a >2 fold-decrease in mRNA expression compared to untreated controls. Homeobox ge...

Anti-angiogenic collagen fragment arresten is increased from 16 weeks' gestation in pre-eclamptic plasma

Placenta, Jan 29, 2015

Arresten and canstatin are endogenous anti-angiogenic factors derived from type IV collagen α-cha... more Arresten and canstatin are endogenous anti-angiogenic factors derived from type IV collagen α-chains COL4A1 and COL4A2 respectively. While their functions are explored in cancer studies, little is known about their role in pregnancy. Pre-eclampsia (PE) is a common, serious hypertensive disorder of pregnancy that is characterised by systemic endothelial dysfunction. COL4A1 and COL4A2 are maternal PE susceptibility genes that have increased mRNA expression in PE decidua. Our study aim was to determine the levels of arresten and canstatin in plasma and decidua from PE and gestational age matched normotensive patients. Plasma was collected from normotensive (n = 44) and PE (n = 39) women during the second and third trimesters of pregnancy. Third trimester decidua was collected at delivery from normotensive and PE women (n = 4 each). Levels of arresten and canstatin were determined by Western immunoblotting. Arresten levels were significantly increased in second and third trimester PE pl...

Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

Stem cells international, 2015

Neurodegeneration is the umbrella term for the progressive loss of structure or function of neuro... more Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are pe...

A distal-less class homeobox gene, DLX4, is a candidate for regulating epithelial-mesenchymal cell interactions in the human placenta

Placenta

Homeobox genes of the Distal-less (Dlx) family are expressed in the vertebrate embryo in regions ... more Homeobox genes of the Distal-less (Dlx) family are expressed in the vertebrate embryo in regions where epithelial cell layers contact adjacent mesenchymal cells. This study shows that the human Dlx family member, DLX4, is expressed in the placenta, primarily in regions where epithelial and mesenchymal cell layers contact. In situ hybridization studies at first trimester human placental sections revealed that DLX4 was expressed predominantly in the cytotrophoblast stem cell layer. In term placenta, DLX4 was expressed in the syncytiotrophoblast. Northern analysis revealed two DLX4 transcripts in first trimester placenta of 2.8 and 3.0 kb. Elevated levels of DLX4 mRNA were detected in a choriocarcinoma derived cell line when compared with a cytotrophoblast cell line and normal placenta. This is the first study to show that a member of the Dlx family of homeobox genes is expressed in regions of epithelial and mesenchymal cell layer contact in the human. Accumulated evidence from several...

Decidual mesenchymal stem cells have reduced resistance to oxidative stress in preeclampsia, which is restored by the aldehyde dehydrogenase agonist Alda-1

Placenta, 2013

Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes

PloS one, 2015

Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic compone... more Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examin...

Aβ1-42 oligomer-induced leakage in an in vitro blood brain barrier model is associated with upregulation of RAGE and metalloproteinases, and downregulation of tight junction scaffold proteins

Journal of neurochemistry, Jan 11, 2015

Accumulating evidence indicates that abnormal deposition of amyloid-β (Aβ) peptide in the brain i... more Accumulating evidence indicates that abnormal deposition of amyloid-β (Aβ) peptide in the brain is responsible for endothelial cell (EC) damage and consequently leads to blood-brain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Aβ1-42, and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5 and Occludin) were decreased. Through comparisons of the effects of the different components of Aβ1-42 , including monomer (Aβ1-42 -Mono), oligomer (Aβ1-42 -Oligo) and fibril (Aβ1-42 -Fibril), our data confirmed that Aβ1-42 -Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in AD. We found that the incubation of bEnd.3 cells with Aβ1-42 significantly upregulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RA...

Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins

Molecular and cellular biology, 1996

We reported the identification of a new family of DNA-binding proteins from our characterization ... more We reported the identification of a new family of DNA-binding proteins from our characterization of the dead ringer (dri) gene of Drosophila melanogaster. We show that dri encodes a nuclear protein that contains a sequence-specific DNA-binding domain that bears no similarity to known DNA-binding domains. A number of proteins were found to contain sequences homologous to this domain. Other proteins containing the conserved motif include yeast SWI1, two human retinoblastoma binding proteins, and other mammalian regulatory proteins. A mouse B-cell-specific regulator exhibits 75% identity with DRI over the 137-amino-acid DNA-binding domains of these proteins, indicating a high degree of conservation of this domain. Gel retardation and optimal binding site screens revealed that the in vitro sequence specificity of DRI is strikingly similar to that of many homeodomain proteins, although the sequence and predicted secondary structure do not resemble a homeodomain. The early general express...