Clinical Focus


  • Cardiovascular Medicine
  • Cardiovascular Disease

Academic Appointments


Professional Education


  • Doctor of Medicine, Harvard University (2011)
  • Bachelor of Science, Massachusetts Institute of Technology (2006)
  • Board Certification: Adult Comprehensive Echocardiography, National Board of Echocardiography (2017)
  • Fellowship:Stanford School of Medicine (2017) CA
  • Residency:Stanford School of Medicine (2014) CA
  • Medical Education:Harvard Medical School (2011) MA
  • Residency, Stanford University Medical Center, Internal Medicine (2014)
  • Board Certification, American Board of Internal Medicine, Internal Medicine (2014)
  • Fellowship, Stanford University Medical Center, Cardiovascular Medicine (2017)
  • Board Certification, American Board of Internal Medicine, Cardiovascular Medicine (2017)

All Publications


  • Large-Scale Single-Cell RNA-Seq Reveals Molecular Signatures of Heterogeneous Populations of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells. Circulation research Paik, D. T., Tian, L., Lee, J., Sayed, N., Chen, I. Y., Rhee, S., Rhee, J., Kim, Y., Wirka, R. C., Buikema, J. W., Wu, S. M., Red-Horse, K., Quertermous, T., Wu, J. C. 2018

    Abstract

    Rationale: Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering a wide gamut of translational and clinical applications. However, inefficiency of the currently available iPSC-EC differentiation protocol and underlying heterogeneity of derived iPSC-ECs remain as major limitations of iPSC-EC technology. Objective: Here we performed droplet-based single-cell RNA-sequencing (scRNA-seq) of the human iPSCs following iPSC-EC differentiation. Droplet-based scRNA-seq enables analysis of thousands of cells in parallel, allowing comprehensive analysis of transcriptional heterogeneity. Methods and Results: Bona fide iPSC-EC cluster was identified by scRNA-seq, which expressed high levels of endothelial-specific genes. iPSC-ECs, sorted by CD144 antibody-conjugated magnetic sorting, exhibited standard endothelial morphology and function including tube formation, response to inflammatory signals, and production of nitric oxide. Non-endothelial cell populations resulting from the differentiation protocol were identified, which included immature and atrial-like cardiomyocytes, hepatic-like cells, and vascular smooth muscle cells. Furthermore, scRNA-seq analysis of purified iPSC-ECs revealed transcriptional heterogeneity with four major subpopulations, marked by robust enrichment of CLDN5, APLNR, GJA5, and ESM1 genes respectively. Conclusions: Massively parallel, droplet-based scRNA-seq allowed meticulous analysis of thousands of human iPSCs subjected to iPSC-EC differentiation. Results showed inefficiency of the differentiation technique, which can be improved with further studies based on identification of molecular signatures that inhibit expansion of non-endothelial cell types. Subtypes of bona fide human iPSC-ECs were also identified, allowing us to sort for iPSC-ECs with specific biological function and identity.

    View details for DOI 10.1161/CIRCRESAHA.118.312913

    View details for PubMedID 29986945

  • Dyslipidaemia: In vivo genome editing of ANGPTL3: a therapy for atherosclerosis? Nature reviews. Cardiology Rhee, J., Wu, J. C. 2018; 15 (5): 259–60

    View details for DOI 10.1038/nrcardio.2018.38

    View details for PubMedID 29618844

  • Cardiac Cell Cycle Activation as a Strategy to Improve iPSC-Derived Cardiomyocyte Therapy. Circulation research Rhee, J. W., Wu, J. C. 2018; 122 (1): 14–16

    View details for DOI 10.1161/CIRCRESAHA.117.312287

    View details for PubMedID 29301838

    View details for PubMedCentralID PMC5773069

  • Human iPSC-Derived Endothelial Cells Predict Predilection to Atherogenesis by Endothelial Proinflammatory Activation Paik, D. T., Kim, Y., Rhee, J., Yi, H., Mishra, R., Wu, J. C. LIPPINCOTT WILLIAMS & WILKINS. 2017: E98
  • Navigating Genetic and Phenotypic Uncertainty in Left Ventricular Noncompaction CIRCULATION-CARDIOVASCULAR GENETICS Rhee, J., Grove, M. E., Ashley, E. A. 2017; 10 (4)
  • Incremental Value of Deformation Imaging and Hemodynamics Following Heart Transplantation: Insights From Graft Function Profiling. JACC. Heart failure Kobayashi, Y., Sudini, N. L., Rhee, J. W., Aymami, M., Moneghetti, K. J., Bouajila, S., Kobayashi, Y., Kim, J. B., Schnittger, I., Teuteberg, J. J., Khush, K. K., Fearon, W. F., Haddad, F. 2017; 5 (12): 930–39

    Abstract

    This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT).Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT.Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality.A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.

    View details for DOI 10.1016/j.jchf.2017.10.011

    View details for PubMedID 29191301

  • Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review. JAMA cardiology Nguyen, P. K., Neofytou, E., Rhee, J., Wu, J. C. 2016; 1 (8): 953-962

    Abstract

    Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist.To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them.Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included.One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity.Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

    View details for DOI 10.1001/jamacardio.2016.2750

    View details for PubMedID 27579998

  • Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review. JAMA cardiology Nguyen, P. K., Rhee, J., Wu, J. C. 2016; 1 (7): 831-841

    Abstract

    Stem cell therapy is a promising treatment strategy for patients with heart failure, which accounts for more than 10% of deaths in the United States annually. Despite more than a decade of research, further investigation is still needed to determine whether stem cell regenerative therapy is an effective treatment strategy and can be routinely implemented in clinical practice.To describe the progress in cardiac stem cell regenerative therapy using adult stem cells and to highlight the merits and limitations of clinical trials performed to date.Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 26, 2016. Twenty-nine randomized clinical trials and 7 systematic reviews and meta-analyses were included in this review.Although adult stem cells were once believed to have the ability to create new heart tissue, preclinical studies suggest that these cells release cardioprotective paracrine factors that activate endogenous pathways, leading to myocardial repair. Subsequent randomized clinical trials, most of which used autologous bone marrow mononuclear cells, have found only a modest benefit in patients receiving stem cell therapy. The lack of a significant benefit may result from variations in trial methods, discrepancies in reporting, and an overreliance on surrogate end points.Although stem cell therapy for cardiovascular disease is not yet ready for routine clinical application, significant progress continues to be made. Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies.

    View details for DOI 10.1001/jamacardio.2016.2225

    View details for PubMedID 27557438

  • Human-induced pluripotent stem cell approaches to model inborn and acquired metabolic heart diseases. Current opinion in cardiology Chanana, A. M., Rhee, J., Wu, J. C. 2016; 31 (3): 266-274

    Abstract

    The article provides an overview of advances in the induced pluripotent stem cell field to model cardiomyopathies of inherited inborn errors of metabolism and acquired metabolic syndromes in vitro.Several inborn errors of metabolism have been studied using 'disease in a dish' models, including Pompe disease, Danon disease, Fabry disease, and Barth syndrome. Disease phenotypes of complex metabolic syndromes, such as diabetes mellitus and aldehyde dehydrogenase 2 deficiency, have also been observed.Differentiation of patient and disease-specific induced pluripotent stem cell-derived cardiomyocytes has provided the capacity to model deleterious cardiometabolic diseases to understand molecular mechanisms, perform drug screens, and identify novel drug targets.

    View details for DOI 10.1097/HCO.0000000000000277

    View details for PubMedID 27022891

    View details for PubMedCentralID PMC4974114

  • Continuous flow left ventricular assist device placement complicated by aortic valve thrombus and myocardial infarction INTERNATIONAL JOURNAL OF CARDIOLOGY Kim, J. B., Rhee, J., Brenner, D. A., Ha, R., Banerjee, D., Yeung, A. C., Tremmel, J. A. 2014; 176 (3): E102-E103
  • Clinical Features, Use of Evidence-Based Therapies, and Cardiovascular Outcomes Among Patients With Chronic Kidney Disease Following Non-ST-Elevation Acute Coronary Syndrome CLINICAL CARDIOLOGY Rhee, J., Wiviott, S. D., Scirica, B. M., Gibson, C. M., Murphy, S. A., Bonaca, M. P., Morrow, D. A., Mega, J. L. 2014; 37 (6): 350-356

    Abstract

    Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular events following acute coronary syndrome (ACS). The underlying pathobiology and optimal treatments for this population continue to be evaluated.Patients with CKD will receive fewer evidence-based therapies and experience high rates of adverse cardiovascular events in both the short- and long term.The MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36) trial randomized non-ST-elevation ACS patients to ranolazine or placebo, with no exclusion for renal dysfunction (except dialysis). We conducted a prespecified analysis among 6543 patients based on the degree of CKD.Patients with worse renal function were older with more comorbidities (P < 0.0001 for each). They were less likely to receive evidence-based cardiovascular medicines (P < 0.04 for each). Rates of an early invasive management strategy varied based on renal function; however, among patients with the highest TIMI risk scores, the rates of an early invasive management strategy were similar regardless of glomerular filtration rate (GFR) (Pinteraction = 0.005). Lower GFR was associated with increased rates of cardiovascular disease or myocardial infarction in the short and long term, even after adjustment (GFR <30 vs ≥90 mL/min/1.73 m(2) ; hazard ratio [HR]: 3.24 [95% confidence interval {CI}: 1.26-8.38] through 7 days and HR: 2.12 [95% CI: 1.33-3.39] through 1 year). The effect of ranolazine vs placebo on clinical outcomes was similar among those with and without CKD (Pinteraction = not significant).Following ACS, patients with renal dysfunction had more cardiovascular risk factors but were less likely to receive evidence-based medical therapies. A strong graded, independent relationship between the degree of CKD and poor clinical outcomes was observed over time. Continued efforts to optimize ACS treatment strategies in patients with CKD are warranted.

    View details for DOI 10.1002/clc.22253

    View details for Web of Science ID 000337597900005

    View details for PubMedID 24481910

  • Elevated Right Ventricular Operant Diastolic Elastance Strongly Predicts Increased Risk of Mortality Following Heart Transplantation Rhee, J., Sudini, N. L., Pham, M., Fearon, W., Lee, D., Beygui, R. E., Montoya, J. G., Wu, J. C., Vrtovec, B., Hunt, S. A., Haddad, F. LIPPINCOTT WILLIAMS & WILKINS. 2013
  • Advances in nanotechnology for the management of coronary artery disease TRENDS IN CARDIOVASCULAR MEDICINE Rhee, J., Wu, J. C. 2013; 23 (2): 39-45

    Abstract

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix.

    View details for DOI 10.1016/j.tcm.2012.08.009

    View details for Web of Science ID 000315016200003

    View details for PubMedID 23245913

    View details for PubMedCentralID PMC3566293

  • The Effect of Age on Outcomes of Coronary Artery Bypass Surgery Compared With Balloon Angioplasty or Bare-Metal Stent Implantation Among Patients With Multivessel Coronary Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Flather, M., Rhee, J., Boothroyd, D. B., Boersma, E., Brooks, M. M., Carrie, D., Clayton, T. C., Danchin, N., Hamm, C. W., Hueb, W. A., King, S. B., Pocock, S. J., Rodriguez, A. E., Serruys, P., Sigwart, U., Stables, R. H., Hlatky, M. A. 2012; 60 (21): 2150-2157

    Abstract

    This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI).Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain.Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year.Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina.Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages.

    View details for DOI 10.1016/j.jacc.2012.08.982

    View details for Web of Science ID 000311077600004

  • In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid-polymeric nanoparticles PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chan, J. M., Rhee, J., Drum, C. L., Bronson, R. T., Golomb, G., Langer, R., Farokhzad, O. C. 2011; 108 (48): 19347-19352

    Abstract

    Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid-polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD.

    View details for DOI 10.1073/pnas.1115945108

    View details for Web of Science ID 000297463100052

    View details for PubMedID 22087004

  • Spatiotemporal controlled delivery of nanoparticles to injured vasculature PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chan, J. M., Zhang, L., Tong, R., Ghosh, D., Gao, W., Liao, G., Yuet, K. P., Gray, D., Rhee, J., Cheng, J., Golomb, G., Libby, P., Langer, R., Farokhzad, O. C. 2010; 107 (5): 2213-2218

    Abstract

    There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.

    View details for DOI 10.1073/pnas.0914585107

    View details for Web of Science ID 000274296300074

    View details for PubMedID 20133865