A5089701670- Renal and related cancers
- Mesenchymal stem cell research
- Chronic Kidney Disease and Diabetes
- Genetic and Kidney Cyst Diseases
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Neonatal Respiratory Health Research
- Renal Diseases and Glomerulopathies
- Birth, Development, and Health
- Immune cells in cancer
- Acute Kidney Injury Research
- Pregnancy-related medical research
- Urological Disorders and Treatments
- Pregnancy and preeclampsia studies
- Organ Donation and Transplantation
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Phagocytosis and Immune Regulation
- Pediatric Urology and Nephrology Studies
- Epigenetics and DNA Methylation
- Bone and Dental Protein Studies
- Renal and Vascular Pathologies
- Ureteral procedures and complications
- Atherosclerosis and Cardiovascular Diseases
Monash University
2016-2025
Australian Regenerative Medicine Institute
2013-2024
Monash Health
2023
Taranaki Base Hospital
2023
The Royal Melbourne Hospital
2018-2023
Discovery Institute
2017-2020
National Institutes of Health
2020
Yale University
2020
Harvard University
2020
Rockefeller University
2020
The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney a robust and sustainable manner. Using bioluminescence imaging mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed damaged kidneys upregulated miR-let7c gene expression, compared nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated injury...
There is some evidence, mainly from rodent studies, that any factor which alters the final total number of nephrons formed, during nephrogenesis, will result in hypertension adult life. Sheep, programmed to become hypertensive by exposure synthetic glucocorticoid (dexamethasone, 0.48 mg h-1, for 48 h) early development (~27 days gestation), were killed at 7 years age, and had nephron counting performed unbiased stereology. Mean arterial pressure was 83 +/- 4 mmHg dexamethasone (DEX) group (n...
OBJECTIVE A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard progression nephropathy, suggesting other mechanism(s) are involved pathogenesis diabetic nephropathy (diabetic nephropathy). We have previously demonstrated endothelial-mesenchymal-transition (EndoMT) contributes to development renal interstitial fibrosis independently microalbuminuria mice streptozotocin (STZ)-induced...
The loss of glomerular podocytes is a key event in the progression chronic kidney disease resulting proteinuria and declining function. Podocytes are slow cycling cells that considered terminally differentiated. Here we provide first report directed differentiation induced pluripotent stem (iPS) to generate with podocyte features. iPS-derived share morphological phenotype analogous cultured human podocytes. Following 10 days differentiation, iPS had an up-regulated expression mRNA protein...
Macrophages accumulate in blood vessels during hypertension. However, their contribution to vessel remodeling is unknown. In the present study, we examined polarization state of macrophages (M1/M2) aortas mice hypertension and investigated whether antagonism chemokine receptors involved macrophage accumulation reduces pressure (BP). Mice treated with ANG II (0.7 mg·kg −1 ·day , 14 days) had elevated systolic BP (158 ± 3 mmHg) compared saline-treated animals (122 mmHg). Flow cytometry...
Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although reparative mechanisms interaction with macrophages have not been elucidated. This study investigated potential of human bone marrow-derived MSCs traced their homing patterns following administration to mice ischemia-reperfusion (IR) using whole body bioluminescence imaging. The effect on macrophage phenotype direct indirect coculture was assessed qPCR. Human cytokine...
Infiltration of macrophages into the artery wall plays detrimental roles during hypertension by promoting vascular inflammation and endothelial dysfunction, it occurs via a chemo-attractant action chemokines on macrophage cytokine receptors. We sought to identify key chemokine receptors associated with infiltration deoxycorticosterone acetate (DOCA)/salt-induced in mice evaluate impact pharmacological inhibition these blood pressure leukocyte accumulation. Mice treated DOCA/salt for 21 days...
The cellular origins of glomerulosclerosis involve activation parietal epithelial cells (PECs) and progressive podocyte depletion. While mammalian target rapamycin-mediated (mTOR-mediated) hypertrophy is recognized as an important signaling pathway in the context glomerular disease, role a compensatory mechanism preventing PEC remains poorly understood. In this study, we show that mTOR activation-related genes were both upregulated intercorrelated biopsies from patients with focal segmental...
A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin transcriptional changes across 22 murine cell types, analyzed alongside previous mouse human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during aging, are enriched for cell-type identity TFBSs. Conversely,...
The end point of immune and nonimmune renal injury typically involves glomerular tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to fibrosis, less is known about mechanisms promote cellular repair tissue remodeling. Described a model after reversal unilateral ureteral obstruction (UUO) in male C57bl/6J mice. Male mice (20 25 g) underwent 10 d UUO with or without 1, 2, 4, 6 wk (R-UUO). resulted cortical tubular cell atrophy dilation conjunction an...
Side population (SP) cells in the adult kidney are proposed to represent a progenitor population. However, size, origin, phenotype, and potential of SP has been controversial. In this study, fraction embryonic kidneys represented 0.1 0.2% total viable cell The immunophenotype expression profile was distinct from that bone marrow cells, suggesting they resident nonhematopoietic Affymetrix profiling implicated role for Notch signaling used identify markers SP. Localization by situ...
Abstract Recent evidence suggests that bone marrow (BM)-derived cells may integrate into the kidney, giving rise to functional renal cell types, including endothelial and epithelial myofibroblasts. BM-derived can contribute repair of peritubular capillary (PTC) network following acute ischemic injury. However, fate regulation during progression chronic disease remains unclear. Using chimeric mice transplanted with enhanced green fluorescent protein (EGFP)-expressing BM, we demonstrate number...
Renal primary cilia are sensory antennas required for the maintenance of normal epithelial differentiation and proliferation in kidney, but they also have a potential role during renal injury repair. In mice, tubular damage causes an increase length cilia, which may modify their sensitivity Here, we investigated whether alteration cilium is clinically relevant. Using biopsies human transplants that suffered acute necrosis transplantation, compared with function. Serial showed resulted more...
Abstract Background Macrophages are traditionally associated with inflammation and host defence, however a greater understanding of macrophage heterogeneity is revealing their essential roles in non-immune functions such as development, homeostasis regeneration. In organs including the brain, kidney, mammary gland pancreas, macrophages reside large numbers provide regulatory that shape organ development maturation. However, role lung potential implications modulation promotion maturation...
The recent introduction of technologies capable reprogramming human somatic cells into induced pluripotent stem (iPS) offers a unique opportunity to study many aspects neurodegenerative diseases in vitro that could ultimately lead novel drug development and testing. Here, we report for the first time dermal fibroblasts from patient with relapsing-remitting Multiple Sclerosis (MS) were reprogrammed pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4, c-MYC). MSiPS...
Glomerular injury and podocyte loss leads to secondary tubulointerstitial damage the development of fibrosis. The possibility genetically reprogramming adult cells, termed induced pluripotent stem cells (iPS), may pave way for patient-specific stem-cell-based therapies. Here, we reprogrammed normal human mesangial pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4 c-Myc). kidney iPS (kiPS) resembled embryonic stem-cell-like colonies in morphology gene expression:...
Reports indicate that germ-line stem cells present in adult mice can rapidly generate new oocytes and contribute to the primordial follicle reserve following conditions of ovotoxic stress. We further investigated hypothesis have capacity by monitoring numbers throughout postnatal life depletion exposure doxorubicin (DXR), trichostatin A (TSA), or whole-body γ-irradiation. show number remains stable C57BL/6 between ages 25 100 days. However, within 2 days treatment with DXR TSA, had declined...
Chronic kidney disease (CKD) results from the development of fibrosis, ultimately leading to end-stage renal (ESRD). Although human bone marrow-derived mesenchymal stem cells (MSCs) can accelerate repair following acute injury, establishment fibrosis during CKD may affect their potential influence regeneration capacity. Here we tested novel combination MSCs with antifibrotic serelaxin and protect 7 d post-unilateral ureteral obstruction (UUO), when is established. Male C57BL6 mice were...