A5054409731- Renal and related cancers
- Renal cell carcinoma treatment
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Ion Transport and Channel Regulation
- Genetic and Kidney Cyst Diseases
- Bioinformatics and Genomic Networks
- Kruppel-like factors research
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Iron Metabolism and Disorders
- Hormonal Regulation and Hypertension
- Cancer-related Molecular Pathways
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Histone Deacetylase Inhibitors Research
- Eicosanoids and Hypertension Pharmacology
- Hemoglobinopathies and Related Disorders
- Electrolyte and hormonal disorders
- Genetic Syndromes and Imprinting
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
Boston University
2002-2023
Boston Medical Center
1999-2023
University Medical Center
1998-2016
Oregon Health & Science University
2013
Brigham and Women's Hospital
2013
Harvard University
1997-2013
Massachusetts General Hospital
1999
Foundation for Growth Science
1999
Beth Israel Deaconess Medical Center
1997
Jerusalem College of Technology
1996
The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found both disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated RCC- tumors. We therefore assessed effect product on VEGF expression. promoter-luciferase constructs were transiently cotransfected with wild-type (wt-VHL) vector several lines, including 293...
Renal cell carcinoma is a common malignancy that often presents as metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal carcinogenesis, number genome-wide expression profiling studies have been performed. Surprisingly, very poor agreement among these to genes differentially regulated. better understand this lack we profiled tumor gene using microarrays (45,000 probe sets) and compare our analysis previous microarray studies. We...
The transcription factor Sp1 is ubiquitously expressed and plays a significant role in the constitutive induced expression of variety mammalian genes may even contribute to tumorigenesis. Here, we describe novel pathway whereby promotes vascular permeability factor/vascular endothelial growth (VPF/VEGF), potent angiogenic factor, by interacting directly specifically with protein kinase C zeta (PKC zeta) isoform renal cell carcinoma. PKC binds phosphorylates zinc finger region Sp1. Moreover,...
Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss function metastasis suppressor genes is major rate-limiting step in progression that prevents the formation new colonies at distal sites. However, discovery using genomic efforts has been slow, potentially due their primary regulation by epigenetic mechanisms. Here, we report use model cell lines with same genetic lineage for identification novel gene, serum deprivation...
We recently reported a novel intracellular mechanism of renal Na-K-ATPase regulation by agents that increase cell cAMP, which involves protein kinase A-phospholipase A2 and is mediated one or more arachidonic acid metabolites (Satoh, T., H. T. Cohen, A. I. Katz. 1992. J. Clin. Invest. 89:1496). The present studies were, therefore, designed to assess the role eicosanoids in modulation activity rat cortical collecting duct. effect various cAMP agonists (dopamine, fenoldopam, vasopressin,...
We have reported that dopamine (DA) inhibits Na-K-ATPase activity in the cortical collecting duct (CCD) by stimulating DA1 receptor, and present study was designed to evaluate mechanism of this effect. Short-term exposure (15-30 min) microdissected rat CCD DA, a agonist (fenoldopam), vasopressin (AVP), forskolin, or dibutyryl cAMP (dBcAMP), which increase content different mechanisms, strongly (approximately 60%) inhibited activity. 2',5'-dideoxyadenosine, an inhibitor adenylate cyclase,...
We performed deletion analysis of <i>WT1</i>-reporter constructs containing up to 24 kilobases 5′-flanking and first intron <i>WT1</i> sequence in stably transfected cultured cells as an unbiased approach identify cis elements critical for transcription. Although not a tissue-specific element, proximate 9-base pair CTC repeat accounted ~80% transcription this assay. Enhancer activity the element mutated versions correlated completely with their ability form DNA-protein complex gel shifts....
We recently reported a novel intracellular mechanism of Na-K-adenosinetriphosphatase (Na-K-ATPase) regulation in the cortical collecting duct (CCD) by agents that increase cell adenosine 3',5'-cyclic monophosphate (cAMP), which involves stimulation protein kinase A (PKA) and phospholipase A2 (PLA2). now determined whether this also operates other nephron segments. In medullary thick ascending limb (MTAL) dopamine, DA1 agonist fenoldopam, forskolin, or dibutyryl-cAMP inhibited Na-K-ATPase...
Abstract Cancer is an increasing and major problem after solid organ transplantation. In part, the increased cancer risk associated with use of immunosuppressive agents, especially calcineurin inhibitors. We propose that effect inhibitors on expression vascular endothelial growth factor (VEGF) leads to angiogenic milieu favors tumor growth. Here, we used 786-0 human renal cells investigate cyclosporine (CsA) VEGF expression. Using a full-length promoter-luciferase construct, found CsA...
Regulation of global chromatin acetylation is important for remodeling. A small family Jade proteins includes Jade-1L, Jade-2, and Jade-3, each bearing two mid-molecule tandem plant homology domain (PHD) zinc fingers. We previously demonstrated that the short isoform Jade-1L protein, Jade-1, associated with endogenous histone acetyltransferase (HAT) activity. It has been found Jade-1L/2/3 co-purify a novel HAT complex, consisting HBO1, ING4/5, Eaf6. investigated role Jade-1/1L in HBO1...
Medical therapies are lacking for advanced renal cancer, so there is a great need to understand its pathogenesis. Most cancers have defects in the von Hippel-Lindau tumor suppressor pVHL. The mechanism by which pVHL protein functions suppression remains unclear. Jade-1 short-lived, kidney-enriched transcription factor that stabilized direct interaction with Loss of stabilization correlates cancer risk, making relationship between and compelling. We report expression was barely detectable all...
Autosomal dominant polycystic kidney disease (ADPKD) is caused by germ line mutations in at least three ADPKD genes.Two recently isolated genes, PKD1 and PKD2, encode integral membrane proteins of unknown function.We found that PKD2 upregulated AP-1-dependent transcription human embryonic 293T cells.The PKD2-mediated AP-1 activity was dependent upon activation the mitogen-activated protein kinases p38 JNK1 kinase C (PKC) , a calcium-independent PKC isozyme.Staurosporine, but not calcium...
Abstract The von Hippel-Lindau (VHL) gene is the major renal cancer in adults. mechanism of tumor suppression by VHL protein only partly elucidated. loss increases expression hypoxia-inducible factor α transcription factors. However, clinical and biochemical data indicate that factors are necessary but not sufficient for tumorigenesis, which suggests other effector pathways involved. Jade-1 interacts strongly with most highly expressed proximal tubules, precursor cells cancer. Short-lived...
Abstract Renal disease is common in sickle cell anemia. In this exploratory work, we used data from a longitudinal study of the natural history to examine hypothesis that polymorphisms (SNPs) selected candidate genes are associated with glomerular filtration rate (GFR). DNA samples and clinical laboratory were available for 1,140 patients GFR was estimated using Cockcroft–Gault Schwartz formulas adults children, respectively. We examined ∼175 haplotype tagging (ht) SNPs about 70 TGFβ/BMP...
VHL is the causative gene for both von Hippel-Lindau (VHL) disease and sporadic clear-cell renal cancer. We showed earlier that downregulates vascular endothelial growth factor transcription by directly binding inhibiting transcriptional activator Sp1. have now mapped Sp1-binding domain to amino acids 96-122. The 96-122 disproportionately affected substitution mutations, which interfere with VHL–Sp1 interaction. Deletion of prevents effects on Sp1 DNA target expression, indicating...
Jade-1 was identified as a protein partner of the von Hippel-Lindau tumor suppressor pVHL. The interaction and pVHL correlates with renal cancer risk. We have investigated molecular function Jade-1. has two zinc finger motifs called plant homeodomains (PHD). A line evidence suggests that PHD functions in chromatin remodeling protein-protein interactions. determined cellular localization examined whether might transcriptional histone acetyltransferase (HAT) functions. Biochemical cell...
The von Hippel-Lindau (VHL) tumor suppressor pVHL is lost in the majority of clear-cell renal cell carcinomas (RCC). Activation PI3K/AKT/mTOR pathway also common RCC, with PTEN loss occurring approximately 30% cases, but other mechanisms responsible for activating AKT at a wider level this setting are undefined. Plant homeodomain protein Jade-1 (PHF17) candidate stabilized by pVHL. Here, using kinase arrays, we identified phospho-AKT1 as an important target Jade-1. Overexpressing or...