A5020498665- Pulmonary Hypertension Research and Treatments
- Congenital Heart Disease Studies
- Cardiovascular Function and Risk Factors
- Cardiac Structural Anomalies and Repair
- Cardiac Valve Diseases and Treatments
- Mitochondrial Function and Pathology
- Mechanical Circulatory Support Devices
- Heart Failure Treatment and Management
- Cardiovascular Effects of Exercise
- Cardiac Arrest and Resuscitation
- Receptor Mechanisms and Signaling
- Cardiomyopathy and Myosin Studies
- Cardiac Arrhythmias and Treatments
- Adipose Tissue and Metabolism
- Congenital heart defects research
- MicroRNA in disease regulation
- Tissue Engineering and Regenerative Medicine
- Coronary Artery Anomalies
- Cardiac electrophysiology and arrhythmias
- Cardiac Ischemia and Reperfusion
- Transplantation: Methods and Outcomes
- Diabetes Management and Research
- Cardiac Fibrosis and Remodeling
- Circular RNAs in diseases
- Cardiovascular Disease and Adiposity
Stanford University
2016-2025
Cardiovascular Institute of the South
2015-2025
Carbon180
2025
Lucile Packard Children's Hospital
2010-2024
Narayana Dental College and Hospital
2023
Palo Alto University
2022
Columbia University
1996-2021
St.John's Medical College Hospital
2021
Cardiovascular Institute Hospital
2021
Stanford Medicine
2016-2020
Dysfunctional bone morphogenetic protein receptor-2 (BMPR2) signaling is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We used a transcriptional high-throughput luciferase reporter assay to screen 3,756 FDA-approved drugs and bioactive compounds for induction BMPR2 signaling. The best response was achieved with FK506 (tacrolimus), via dual mechanism action as calcineurin inhibitor that also binds FK-binding protein-12 (FKBP12), repressor BMP released FKBP12 from...
Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating structure-function relationships, there still much be learned about mechanisms that link altered cardiac energetics phenotypes. In this work, we test hypothesis changes represent common...
Pulmonary arterial hypertension (PAH) is a life-threatening disorder of the pulmonary circulation associated with loss and impaired regeneration microvessels. Reduced pericyte coverage microvessels pathological feature PAH caused partly by inability pericytes to respond signaling cues from neighboring microvascular endothelial cells (PMVECs). We have shown that activation Wnt/planar cell polarity pathway required for recruitment, but whether production release specific Wnt ligands PMVECs are...
Congenital heart disease (CHD) has a complex genetic etiology, and recent studies suggest that high penetrance de novo mutations may account for only small fraction of disease. In multi-institutional cohort surveyed by exome sequencing, combining analysis 987 individuals (discovery 59 affected trios control trios, replication 100 singletons 533 unaffected singletons) we observe variation at novel known loci related to specific cardiac malformation the atrioventricular septal defect (AVSD)....
Mitochondria play a dual role in the heart, responsible for meeting energetic demands and regulating cell death. Paradigms have held that mitochondrial fission fragmentation are result of pathological stresses, such as ischemia, an indicator poor health, lead to mitophagy However, recent studies demonstrate inhibiting also results decreased function cardiac impairment, suggesting is important maintaining bioenergetic homeostasis.
Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking.
MicroRNAs (miRs) are small, noncoding RNAs that emerging as crucial regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and failure (LVF). However, there no data on their role right (RVH) (RVF). This is a critical question given the RV uniquely at risk patients with congenital right-sided obstructive lesions those systemic RVs. We have developed murine model RVH RVF using pulmonary artery constriction (PAC). miR microarray analysis from PAC vs. control demonstrates altered...
Quantification of protein expression in single cells promises to advance a systems-level understanding normal development. Using bottom-up proteomic workflow and multiplexing quantification by tandem mass tags, we recently demonstrated relative between embryonic (blastomeres) the frog (Xenopus laevis) embryo. In this study, minimize derivatization steps enhance analytical sensitivity use label-free (LFQ) for Xenopus cells. The technology builds on custom-designed capillary electrophoresis...
Pulmonary insufficiency (PI) is a common long-term sequel after repair of tetralogy Fallot, causing progressive right ventricular (RV) dilation and failure. We describe the physiologic molecular characteristics first murine model RV volume overload. PI was created by entrapping pulmonary valve leaflets with sutures. Imaging, catheterization, exercise testing were performed at 1, 3, 6 mo compared sham controls. RNA from free wall hybridized to Agilent whole genome oligonucleotide microarrays....
Rationale: Hypoxia-inducible factor-1α (HIF-1α), an oxygen (O 2 )-sensitive transcription factor, mediates transcriptional responses to low-O tension states. Although acute hypoxia causes pulmonary vasoconstriction and chronic can cause vascular remodeling hypertension, conflicting data exist on the role of HIF-1α in modulating tone. Objective: To investigate smooth muscle cell (SMC)–specific regulating Methods Results: Mice with SMC-specific deletion (SM22α-HIF-1α −/− ) were created test...
Human induced pluripotent stem cellderived cardiomyocytes (hiPSC-CMs) are a powerful platform for uncovering disease mechanisms and assessing drugs efficacy/toxicity.However, the accuracy with which hiPSC-CMs recapitulate contractile remodeling signaling of adult is not fully known.We used b-adrenergic receptor (b-AR) as prototype to determine evolution component expression function during hiPSC-CM maturation.In "early" (less than or equal d 30), b2-ARs primary source cAMP/PKA signaling.With...
Alterations in the ubiquitin-proteasome system (UPS) have been described left ventricular hypertrophy and failure, although results inconsistent. The role of UPS right (RV) (RVH) RV failure (RVF) is unknown. Given greater percent increase mass associated with afterload stress, as present many congenital heart lesions, we hypothesized that alterations could play an important RVH/RVF. expression activity were measured from mice RVH/RVF secondary to pulmonary artery constriction (PAC)....
Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms congenital heart disease, causing progressive right ventricular (RV) dilation failure. Little known the mechanisms underlying this combination preload afterload stressors. We developed murine model PI PS (PI+PS) to identify clinically relevant pathways biomarkers disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated end-diastolic pressures) at 1...
Background In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading RV hypertrophy and eventually failure. The mechanisms that promote transition from stable failure are unknown. We evaluated role mitochondrial bioenergetics in development Methods Results created a murine model overload by pulmonary artery banding compared sham‐operated controls. Gene expression RNA‐sequencing, oxidative stress,...
The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early the pressure-loaded RV. Here we test hypothesis microRNA (miR)-34a, which induced RV hypertrophy and failure (RVF), blocks hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to attenuated angiogenic response increased susceptibility failure.
BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss microvasculature. However, the methods underpinning prior studies did not take into account 3-dimensional (3D) aspects cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to pressure-overloaded RV uncover 3D properties microvascular network and determine whether deficient adaptation contributes failure. METHODS: Heart sections...
The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model gradual RV from and use it delineate reverse-remodelling events.
Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation BMP (bone morphogenetic protein) signaling FK506 (tacrolimus) improved RV by decreasing afterload. therapy further stabilized three end-stage PAH. Whether has direct effects on pressure-overloaded right ventricle yet unknown. We hypothesized that increasing cardiac improves structure and a model fixed afterload...
Background Secondary hemorrhage post total laparoscopic hysterectomy (TLH) is defined as bleeding per vagina after 24 hours up to 6 weeks the primary surgery. The purpose of study determine possible risk factors for secondary TLH and how manage it medically. Methods A prospective observational with all patients who underwent under author from 1st January 2023 31st December 2023, indications requiring suffering vaginum starting until surgery were included in this study. Patients a known...