Honors & Awards
Samuel A. Levine Early Career Clinical Investigator Award Finalist, American Heart Association (2022)
Predoctoral Fellowship, American Heart Association (2022-2023)
Dorothy Dee and Marjorie Helene Boring Trust Award, Stanford Cardiovascular Institute (2021)
Professional Affiliations and Activities
Student, American Heart Association (AHA) (2018 - Present)
Education & Certifications
Bachelor of Arts, University of Chicago (2018)
Service, Volunteer and Community Work
Cardiovascular Clinic Coordinator, Cardinal Free Clinics, Stanford Medicine (8/10/2020 - Present)
Deconvoluting the Cells of the Human Heart with iPSC Technology: Cell Types, Protocols, and Uses.
Current cardiology reports
PURPOSE OF REVIEW: Induced pluripotent stem cells (iPSCs) have become widely adopted tools in cardiovascular biology due to their ability to differentiate into patient-specific cell types. Here, we describe the current protocols, important discoveries, and experimental limitations from the iPSC-derived cell types of the human heart: cardiomyocytes, cardiac fibroblasts, vascular smooth muscle cells, endothelial cells, and pericytes. In addition, we also examine the progress of 3D-based cell culture systems.RECENT FINDINGS: There has been rapid advancement in methods to generate cardiac iPSC-derived cell types. These advancements have led to improved cardiovascular disease modeling, elucidation of interactions among different cell types, and the creation of 3D-based cell culture systems able to provide more physiologically relevant insights into cardiovascular diseases. iPSCs have become an instrumental model system in the toolbox of cardiovascular biologists. Ongoing research continues to advance the use of iPSCs in (1) disease modeling, (2) drug screening, and (3) clinical trials in a dish.
View details for DOI 10.1007/s11886-022-01670-z
View details for PubMedID 35244869
Improvements in patient safety culture: a national Taiwanese survey, 2009-16
INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE
2020; 32 (1): A9–A17
To assess national trends in patient safety culture in Taiwan.A safety attitudes questionnaire (SAQ) was distributed to 144 hospitals from 2009 to 2016 (n = 392 341).Taiwan's medical centers, regional hospitals and community hospitals.Hospital staff in Taiwan.None.5-point Likert scale to assess changes in patient safety culture dimensions (teamwork, safety climate, job satisfaction, stress recognition, management and working conditions) converted to positive response rate (percentage of respondents who answered slightly agree or strongly agree on Likert scale).Dimensions for patient safety culture significantly increased in Taiwan over a period of 8 years, with an all-composite improvement in positive response rate of 4.6% (P < 0.001). Regional hospitals and community hospitals registered an all-composite improvement of 6.7 and 7.0%, respectively, while medical centers improved by 4.0%. Improvements for regional and community hospitals primarily occurred in teamwork (regional hospitals, 10.4% [95% confidence interval [CI], 10.2-10.6]; community hospitals, 8.5% [95% CI, 8.0-9.0]) and safety climate (regional hospitals, 11.1% [95% [CI], 10.9-11.4]; community hospitals, 11.3% [95% CI, 10.7-11.8]) (P < 0.001, all differences). Compared with nurses (5.1%) and pharmaceutical staff (10.6%), physicians improved the least (2.0%). Improvements for nurses and pharmacists were driven by increases in perceptions of teamwork (nurses, 9.8% [95% CI, 9.7-10.0]; pharmaceutical staff, 14.2% [95% CI, 13.4-14.9]) and safety climate (nurses, 9.0% [95% CI, 8.8-9.1]; pharmaceutical staff, 16.4% [95% CI, 15.7-17.2]) (P < 0.001, all differences). At study end, medical centers (55.1%) had greater all-composite measurements of safety culture than regional hospitals (52.4%) and community hospitals (52.2%) while physicians (63.7%) maintained greater measurements of safety culture than nurses (52.1%) and pharmaceutical staff (56.6%).These results suggest patient safety culture improved in Taiwan from 2009 to 2016.
View details for DOI 10.1093/intqhc/mzz099
View details for Web of Science ID 000537406400003
View details for PubMedID 31917449
Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening
EXPERT OPINION ON THERAPEUTIC TARGETS
2020; 24 (1): 47–62
Introduction: Pathological cardiac fibrosis, through excessive extracellular matrix protein deposition from fibroblasts and pro-fibrotic immune responses and vascular stiffening is associated with most forms of cardiovascular disease. Pathological cardiac fibrosis and stiffening can lead to heart failure and arrythmias and vascular stiffening may lead to hypertension. ROCK, a serine/threonine kinase downstream of the Rho-family of GTPases, may regulate many pro-fibrotic and pro-stiffening signaling pathways in numerous cell types.Areas covered: This article outlines the molecular mechanisms by which ROCK in fibroblasts, T helper cells, endothelial cells, vascular smooth muscle cells, and macrophages mediate fibrosis and stiffening. We speculate on how ROCK could be targeted to inhibit cardiovascular fibrosis and stiffening.Expert opinion: Critical gaps in knowledge must be addressed if ROCK inhibitors are to be used in the clinic. Numerous studies indicate that each ROCK isoform may play differential roles in regulating fibrosis and may have opposing roles in specific tissues. Future work needs to highlight the isoform- and tissue-specific contributions of ROCK in fibrosis, and how isoform-specific ROCK inhibitors in murine models and in clinical trials affect the pathophysiology of cardiac fibrosis and stiffening. This could progress knowledge regarding new treatments for heart failure, arrythmias and hypertension and the repair processes after myocardial infarction.
View details for DOI 10.1080/14728222.2020.1712593
View details for Web of Science ID 000506321900001
View details for PubMedID 31906742
- Molecular Mechanisms for Statin Pleiotropy and Possible Clinical Relevance in Cardiovascular Disease Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies Taylor & Francis. 2020; 1
Regulator of G-Protein Signaling 5 Maintains Brain Endothelial Cell Function in Focal Cerebral Ischemia.
Journal of the American Heart Association
Background Regulator of G-protein signaling 5 (RGS5) is a negative modulator of G-protein-coupled receptors. The role of RGS5 in brain endothelial cells is not known. We hypothesized that RGS5 in brain microvascular endothelial cells may be an important mediator of blood-brain barrier function and stroke severity after focal cerebral ischemia. Methods and Results Using a transient middle cerebral artery occlusion model, we found that mice with global and endothelial-specific deletion of Rgs5 exhibited larger cerebral infarct size, greater neurological motor deficits, and increased brain edema. In our in vitro models, we observed increased Gq activity and elevated intracellular Ca2+ levels in brain endothelial cells. Furthermore, the loss of endothelial RGS5 leads to decreased endothelial NO synthase expression and phosphorylation, relocalization of endothelial tight junction proteins, and increased cell permeability. Indeed, RGS5 deficiency leads to increased Rho-associated kinase and myosin light chain kinase activity, which were partially reversed in our in vitro model by pharmacological inhibition of Gq, metabotropic glutamate receptor 1, and ligand-gated ionotropic glutamate receptor. Conclusions Our findings indicate that endothelial RGS5 plays a novel neuroprotective role in focal cerebral ischemia. Loss of endothelial RGS5 leads to hyperresponsiveness to glutamate signaling pathways, enhanced Rho-associated kinase- and myosin light chain kinase-mediated actin-cytoskeleton reorganization, endothelial dysfunction, tight junction protein relocalization, increased blood-brain barrier permeability, and greater stroke severity. These findings suggest that preservation of endothelial RGS5 may be an important therapeutic strategy for maintaining blood-brain barrier integrity and limiting the severity of ischemic stroke.
View details for DOI 10.1161/JAHA.120.017533
View details for PubMedID 32875943
RELATIONSHIP BETWEEN GLOBAL LONGITUDINAL STRAIN AND LEFT VENTRICULAR DIASTOLIC FUNCTION
American College of Cardiology Scientific Session 2019
View details for DOI 10.1016/s0735-1097(19)32281-8
- Rho-Associated Kinase Activity Correlates With the Presence of Diastolic Dysfunction in Patients With Normal Left Ventricular Ejection Fraction American Heart Association Scientific Session 2019 2019
ABL Tyrosine Kinase Inhibitors (TKIs) Are Associated with Increased Rho-Associated Kinase (ROCK) Activity That May Contribute to Vascular Toxicity in Patients with Chronic Myeloid Leukemia (CML)
American Society of Hematology Annual Meeting 2018
View details for DOI 10.1182/blood-2018-99-111201
THE FEASIBILITY OF GLOBAL LONGITUDINAL STRAIN IN CLINICAL PRACTICE AND RELATIONSHIP WITH EJECTION FRACTION
View details for DOI 10.1016/S0735-1097(18)32257-5
Fibroblast deletion of ROCK2 attenuates cardiac hypertrophy, fibrosis, and diastolic dysfunction
2017; 2 (13)
Although left ventricular (LV) diastolic dysfunction is often associated with hypertension, little is known regarding its underlying pathophysiological mechanism. Here, we show that the actin cytoskeletal regulator, Rho-associated coiled-coil containing kinase-2 (ROCK2), is a critical mediator of LV diastolic dysfunction. In response to angiotensin II (Ang II), mutant mice with fibroblast-specific deletion of ROCK2 (ROCK2Postn-/-) developed less LV wall thickness and fibrosis, along with improved isovolumetric relaxation. This corresponded with decreased connective tissue growth factor (CTGF) and fibroblast growth factor-2 (FGF2) expression in the hearts of ROCK2Postn-/- mice. Indeed, knockdown of ROCK2 in cardiac fibroblasts leads to decreased expression of CTGF and secretion of FGF2, and cardiomyocytes incubated with conditioned media from ROCK2-knockdown cardiac fibroblasts exhibited less hypertrophic response. In contrast, mutant mice with elevated fibroblast ROCK activity exhibited enhanced Ang II-stimulated cardiac hypertrophy and fibrosis. Clinically, higher leukocyte ROCK2 activity was observed in patients with diastolic dysfunction compared with age- and sex-matched controls, and correlated with higher grades of diastolic dysfunction by echocardiography. These findings indicate that fibroblast ROCK2 is necessary to cause cardiac hypertrophy and fibrosis through the induction CTGF and FGF2, and they suggest that targeting ROCK2 may have therapeutic benefits in patients with LV diastolic dysfunction.
View details for DOI 10.1172/jci.insight.93187
View details for Web of Science ID 000405181200011
View details for PubMedID 28679962
View details for PubMedCentralID PMC5499369
ROCK as a therapeutic target for ischemic stroke
EXPERT REVIEW OF NEUROTHERAPEUTICS
2017; 17 (12): 1167–77
Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.
View details for DOI 10.1080/14737175.2017.1395700
View details for Web of Science ID 000416022100005
View details for PubMedID 29057688
View details for PubMedCentralID PMC6221831