A5018281724- Renal and related cancers
- Urological Disorders and Treatments
- Pediatric Urology and Nephrology Studies
- Renal cell carcinoma treatment
- Innovations in Medical Education
- Health and Medical Research Impacts
- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Diversity and Career in Medicine
- Family Support in Illness
- Organ Donation and Transplantation
- Childhood Cancer Survivors' Quality of Life
- Ovarian cancer diagnosis and treatment
- Pluripotent Stem Cells Research
- Cancer survivorship and care
- Endometrial and Cervical Cancer Treatments
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Reproductive Biology and Fertility
- Genetic Syndromes and Imprinting
- Tissue Engineering and Regenerative Medicine
- Renal and Vascular Pathologies
- Cell Adhesion Molecules Research
Hospital for Sick Children
2016-2025
University of Toronto
2016-2025
SickKids Foundation
2014-2025
Canadian Institutes of Health Research
2020-2025
Institute of Nutrition, Metabolism and Diabetes
2020-2024
Thomas Jefferson University Hospital
2004-2024
Centre for Global Health Research
2022
Thomas Jefferson University
2007-2021
Jefferson University Hospitals
2021
Stanford University
2021
Glypicans are a family of heparan sulfate proteoglycans that linked to the cell surface through glycosyl–phosphatidylinositol anchor. One member this family, glypican-3 (Gpc3), is mutated in patients with Simpson-Golabi-Behmel syndrome (SGBS). These display pre- and postnatal overgrowth, varying range dysmorphisms. The clinical features SGBS very similar more extensively studied Beckwith-Wiedemann (BWS). Since BWS has been associated biallelic expression insulin-like growth factor II...
The occurrence of approximately 5% common epithelial malignant tumors the ovary can be traced to inheritance risk. One prohylactic strategy decrease probability development disease in individuals within families where this mendelian-dominant pattern is apparent remove ovaries at risk for ovarian cancer. procedure, when done purpose, recommended soon after completion childbearing. Our goal was compare histologic features women increased cancer those no known disease. Ovaries removed...
To elucidate the molecular pathways that modulate renal cyst growth in ADPKD, we performed global gene profiling on cysts of different size (<1 ml, n = 5; 10-20 >50 3) and minimally cystic tissue (MCT, 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133 Plus 2.0 arrays. We used set enrichment analysis to identify overrepresented signaling key transcription factors (TFs) between MCT. found down-regulation kidney epithelial restricted genes (e.g. nephron segment-specific...
Truncating mutations in Gli3, an intracellular effector the SHH-SMO-GLI signaling pathway, cause renal aplasia/dysplasia humans and mice. Yet, pathogenic mechanisms are undefined. Here, we report effect of decreased SHH-SMO on morphogenesis, expression SHH target genes GLI binding to Shh genes. Shhdeficiency or cyclopamine-mediated SMO inhibition disrupted organogenesis, GLI1 GLI2 proteins, but increased GLI3 repressor relative activator. kidney patterning (Pax2 Sall1) cell cycle regulators...
Purpose To identify the prevalence of psychological distress among women with ovarian cancer and to examine association between these symptoms demographic medical variables. Patients Methods Participants were 143 cancer. Forty-eight percent participants had been diagnosed advanced-stage disease (stage III or IV) most (80%) currently receiving treatment. Psychological was assessed following measures: Beck Depression Inventory, Mental Health Impact Events Scale, a questionnaire regarding...
Polycystin-1 (PC1), the product of PKD1 gene mutated in majority autosomal dominant polycystic kidney disease (ADPKD) cases, undergoes a cleavage resulting intracellular release its C-terminal tail (CTT). Here, we demonstrate that PC1 CTT co-localizes with and binds to β-catenin nucleus. This interaction requires nuclear localization motif present as well N-terminal portion β-catenin. The inhibits ability both Wnt ligands activate T-cell factor (TCF) -dependent transcription, major effector...
Henoch-Schonlein purpura is a systemic vasculitis of unknown cause that characterized primarily by abdominal pain, arthritis, and purpuric skin lesions. Abdominal pain the most common gastrointestinal symptom, but intestinal bleeding intussusception may occur. Previous studies have supported use steroids in managing purpura.1,2 Because there are no controlled trials using this disease, their value affecting lesions remains unknown. The purpose retrospective study was to assess effect...
The bone morphogenetic proteins, BMP-2 and OP-1, are candidates for growth factors that control renal branching morphogenesis. We examined their effects in embryonic kidney explants the mIMCD-3 cell model of collecting duct morphogenesis (mIMCD-3 cells derived from terminal inner medullary SV40 mouse). Osteogenic protein-1 (OP-1), at a dose 0.25 nM, increased explant by 30% ( P = 0.001). In contrast, 100-fold greater concentrations OP-1 (28 nM) decreased 10% < was entirely inhibitory...
Obstructive and nonobstructive forms of hydronephrosis (increased diameter the renal pelvis calyces) hydroureter (dilatation ureter) are most frequently detected antenatal abnormalities, yet underlying molecular mechanisms largely undefined. Hedgehog (Hh) proteins control tissue patterning cell differentiation by promoting GLI-dependent transcriptional activation inhibiting processing GLI3 to a repressor. Genetic mutations that generate truncated protein similar in size repressor humans with...
Resilience has been linked to psychological adaptation many challenging life events.The goal was examine 3 coping strategies--expressing positive emotions, reframing of the cancer experience, and cultivating a sense peace meaning in life--as potential mechanisms by which resilience translates quality among women recently diagnosed with gynecological cancer.This cross-sectional study utilized baseline data from participating an ongoing randomized clinical trial (n = 281; mean age, 55 years;...
The clinician-scientist role is critical to the future of health care, and in 2010, Carnegie Report on Educating Physicians focused attention professional identity practicing clinicians. Although limited number, published studies topic suggest that likely a factor determines career sustainability. In contrast clinicians with singular focus clinical practice, clinician-scientists combine two major disciplines, medicine scientific research, bridge discovery care. Despite its importance...
Although research has indicated that illness-related and interpersonal stress are associated with greater psychological distress among cancer patients, little empirical attention been given to mechanisms account for these relationships. In the present study, 2 association between (physical impairment) (family friend unsupportive responses) of 143 ovarian patients were examined cross-sectionally. Separate structural equation models tested whether physical impairment impacted patients' via...
Renal dysplasia, the major cause of childhood renal failure in humans, arises from perturbed morphogenesis and molecular signaling during embryogenesis. Recently, we discovered induction crosstalk between Smad1 beta-catenin TgAlk3QD mouse model medullary cystic dysplasia. Our finding that Myc, a Smad transcriptional target effector epithelial dedifferentiation, is misexpressed dedifferentiated tubules provided basis for investigating coordinate control by disease. Here, report enhanced...
Type X collagen, expressed by hypertrophic chondrocytes, consists of homotrimeric molecules with subunits that are only about one-half the size polypeptides fibrillar collagens. In this report we describe for first time complete primary structure type based on cloning and sequencing cDNA genomic DNA. A comparison between nucleotide sequences DNA clones has also allowed determination exon collagen gene. Our results demonstrate translation product chicken mRNA is 682 amino acid residues long a...
Truncating GLI3 mutations in Pallister-Hall Syndrome with renal malformation suggests a requirement for Hedgehog signaling during development. HH-dependent increases levels of GLI transcriptional activators and decreases processing to shorter repressor. Previously, we showed that Shh-deficiency interrupts early inductive events development manner dependent on Here identify novel function repressor controlling nephron number. During morphogenesis, HH activity, assayed by expression Ptc1-lacZ,...