A5014820840- Vascular Malformations Diagnosis and Treatment
- Intracranial Aneurysms: Treatment and Complications
- Intracerebral and Subarachnoid Hemorrhage Research
- Vascular Anomalies and Treatments
- Moyamoya disease diagnosis and treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Drug Transport and Resistance Mechanisms
- Vascular Malformations and Hemangiomas
- Tracheal and airway disorders
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Pharmacological Effects and Toxicity Studies
- Transplantation: Methods and Outcomes
- Receptor Mechanisms and Signaling
- Genetics, Aging, and Longevity in Model Organisms
- Liver Disease Diagnosis and Treatment
- Sharing Economy and Platforms
- Cardiac electrophysiology and arrhythmias
- Nutrition and Health in Aging
- Adipokines, Inflammation, and Metabolic Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Heart Failure Treatment and Management
- Neonatal Health and Biochemistry
- Genetic Associations and Epidemiology
- Pulmonary Hypertension Research and Treatments
University of California, San Francisco
2012-2023
California Pacific Medical Center
2009-2023
Neurological Surgery
2004-2022
University of New Mexico
2021
University of Toronto
2011-2021
Angioma Alliance
2021
Barrow Neurological Institute
2021
Center for Human Genetics
2008-2018
Columbia University Irving Medical Center
2013
St. Michael's Hospital
2011
Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter salt export pump (BSEP) mutation ABCB11 , encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)—or “neonatal hepatitis” suggesting PFIC—that was associated with HCC studied 11 cases pediatric setting PFIC or PFIC. Archival liver were retrieved immunostained for...
The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation this pathway influences humans, we genotyped 291 variants 30 genes encoding proteins the a cohort of elderly Caucasian women selected from Study Osteoporotic Fractures (SOF). included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) 95.3 2.2y) 603 average-lifespan controls < 79y, 75.7 2.6y)....
Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic develop liver fibrosis. BRIC experience intermittent attacks of that resolve spontaneously. Mutations in ATP8B1 (previously FIC1 ) may result or BRIC. We report the genomic organization mutation analyses 180 families with identified 54 disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense 11 small...
Progressive familial intrahepatic cholestasis type 1 (PFIC1, Byler disease, OMIM 211600) is a severe inherited liver disease caused by mutations in ATP8B1 . member of the 4 subfamily P-type ATPases, which are phospholipid flippases. PFIC1 patients generally develop end-stage before second decade life. The characterized impaired biliary bile salt excretion, but mechanism whereby function results unclear. In mouse model for PFIC1, we observed decreased resistance hepatocanalicular membrane to...
Background and Purpose— Accurate estimates of intracranial hemorrhage (ICH) risk in patients harboring brain arteriovenous malformation (BAVM) are needed to evaluate interventional strategies help guide clinical management. Identification genetic polymorphisms associated with ICH would facilitate stratification BAVM patients. Methods— We identified documented presentation, demographic data, venous drainage pattern, size. Patients were genotyped for 5 3 inflammatory cytokine genes, 9...
Abstract We recently reported that the GG genotype of interleukin‐6 (IL‐6)–174G>C promoter polymorphism is associated with clinical presentation intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL‐6 expression was IL‐6–174G>C genotype, and linked to downstream targets involved angiogenesis vascular instability. Our results showed highest protein levels AVM were IL‐6–174GG (GG: 57.7 ± 20.2; GC: 35.6 26.6; CC: 13.9...
Background and Purpose— Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would associated with an increased risk cardiac injury. Methods— This was a prospective cohort study. The primary outcome variables were serum level troponin I (cTi, abnormal if >1.0 μg/L) left ventricular...
Background and Purpose— The purpose of this study was to quantitatively estimate the relationship between multiplicity brain arteriovenous malformations (bAVMs) diagnosis hereditary hemorrhagic telangiectasia (HHT). Methods— We combined databases from 2 large North American bAVM referral centers, including demographics, clinical presentation, angiographic characteristics, compared patients with HHT non-HHT patients. Logistic regression analysis performed quantify association odds diagnosis....
Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma‐glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding 1 [FIC1] deficiency) or ABCB11 (bile salt export protein [BSEP] deficiency). We investigated outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation these two conditions. conducted a retrospective multicenter study 42 patients FIC1 deficiency (FIC1 patients) 60 BSEP (BSEP who had undergone...
Mutations in ATP8B1, a broadly expressed P-type ATPase, result, through unknown mechanisms, disorders of bile secretion. These vary severity from mild and episodic to progressive with liver failure. We generated Atp8b1 G308V/G308V mutant mice, which carry mutation orthologous that present homozygous form patients the Amish index kindred for severe ATP8B1 disease. In contrast human patients, mice had unimpaired secretion no damage, but showed abnormalities including depressed weight at...
Background and Purpose— Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate stratification identify potential targets for therapeutic intervention. Methods— Patients BAVM were longitudinally followed. Primary outcome was ICH diagnosis; censoring events last follow-up or any treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes:...
The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some the difference. To identify loci influencing BMI, we carried out a pooled analysis genome-wide admixture mapping scans 15,280 from 14 epidemiologic studies. Samples were genotyped at median 1,411 ancestry-informative markers. After adjusting age, sex, and study, BMI was...
<i>Background:</i> Polymorphisms in the proinflammatory cytokine interleukin (IL)-1β gene have been associated with systemic atherogenesis, thrombosis and rupture. The aim of this study was to investigate associations between single nucleotide polymorphisms (SNPs) IL-1β intracranial hemorrhage (ICH) natural course brain arteriovenous malformation (BAVM) patients. <i>Method:</i> Two promoter SNPs (–511C→T, –31T→C) 1 synonymous coding SNP exon 5 at +3953C→T (Phe) were...
Abstract Background Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of myocardial infarction. Recent candidate gene association studies community arrests have focused on limited number biological pathways and yielded conflicting results. We sought identify novel associations in patients with coronary artery disease by performing genome-wide study. Methods Tagging SNPs (n = 338,328) spanning the genome were typed case-control study comparing...
Background: Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped (KRIT1/CCM1) gene, and characterized multiple brain lesions that often result intracerebral hemorrhage (ICH), seizures, neurological deficits. Carriers of same genetic mutation can present with variable symptoms severity disease, suggesting influence modifier factors. Evidence emerging inflammation immune response play a role pathogenesis...