Academic Appointments


Honors & Awards


  • TRISH Postdoctoral Fellowship, TRISH/NASA (2021-2023)
  • TRAM pilot grant, Stanford University (2021-2022)

All Publications


  • Generation of two induced pluripotent stem cell lines from patients suffering from pulmonary hypertension. Stem cell research Chen, G., Orozco, L., Parmisano, S., Jahng, J. W., Vera, C. D., Zhuge, Y., Wu, J. C., Obal, D. 2023; 72: 103218

    Abstract

    Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease, with an estimated 500-1000 new cases diagnosed every year. A portion of these cases may be caused by mutations in the BMPR2 gene, suggesting a possible genetic component in the development of the disease. Here, we report two human induced pluripotent stem cell (iPSC) lines generated from IPAH patients. Both cell lines provide valuable insight into the molecular and cellular mechanisms of IPAH and can be used to further understand the disease.

    View details for DOI 10.1016/j.scr.2023.103218

    View details for PubMedID 37804546

  • SGLT2 inhibitor ameliorates endothelial dysfunction associated with the common ALDH2 alcohol flushing variant. Science translational medicine Guo, H., Yu, X., Liu, Y., Paik, D. T., Justesen, J. M., Chandy, M., Jahng, J. W., Zhang, T., Wu, W., Rwere, F., Zhao, S. R., Pokhrel, S., Shivnaraine, R. V., Mukherjee, S., Simon, D. J., Manhas, A., Zhang, A., Chen, C. H., Rivas, M. A., Gross, E. R., Mochly-Rosen, D., Wu, J. C. 2023; 15 (680): eabp9952

    Abstract

    The common aldehyde dehydrogenase 2 (ALDH2) alcohol flushing variant known as ALDH2*2 affects ∼8% of the world's population. Even in heterozygous carriers, this missense variant leads to a severe loss of ALDH2 enzymatic activity and has been linked to an increased risk of coronary artery disease (CAD). Endothelial cell (EC) dysfunction plays a determining role in all stages of CAD pathogenesis, including early-onset CAD. However, the contribution of ALDH2*2 to EC dysfunction and its relation to CAD are not fully understood. In a large genome-wide association study (GWAS) from Biobank Japan, ALDH2*2 was found to be one of the strongest single-nucleotide polymorphisms associated with CAD. Clinical assessment of endothelial function showed that human participants carrying ALDH2*2 exhibited impaired vasodilation after light alcohol drinking. Using human induced pluripotent stem cell-derived ECs (iPSC-ECs) and CRISPR-Cas9-corrected ALDH2*2 iPSC-ECs, we modeled ALDH2*2-induced EC dysfunction in vitro, demonstrating an increase in oxidative stress and inflammatory markers and a decrease in nitric oxide (NO) production and tube formation capacity, which was further exacerbated by ethanol exposure. We subsequently found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin mitigated ALDH2*2-associated EC dysfunction. Studies in ALDH2*2 knock-in mice further demonstrated that empagliflozin attenuated ALDH2*2-mediated vascular dysfunction in vivo. Mechanistically, empagliflozin inhibited Na+/H+-exchanger 1 (NHE-1) and activated AKT kinase and endothelial NO synthase (eNOS) pathways to ameliorate ALDH2*2-induced EC dysfunction. Together, our results suggest that ALDH2*2 induces EC dysfunction and that SGLT2i may potentially be used as a preventative measure against CAD for ALDH2*2 carriers.

    View details for DOI 10.1126/scitranslmed.abp9952

    View details for PubMedID 36696485

  • Ferroptosis of Pacemaker Cells in COVID-19. Circulation research Nishiga, M., Jahng, J. W., Wu, J. C. 2022; 130 (7): 978-980

    View details for DOI 10.1161/CIRCRESAHA.122.320951

    View details for PubMedID 35357897

  • Generation of two iPSC lines from hypertrophic cardiomyopathy patients carrying MYBPC3 and PRKAG2 variants. Stem cell research Manhas, A., Jahng, J. W., Vera, C. D., Shenoy, S. P., Knowles, J. W., Wu, J. C. 2022; 61: 102774

    Abstract

    Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder characterized by a thick left ventricular wall and an increased risk of arrhythmias, heart failure, and sudden cardiac death. The MYBPC3 and PRAKG2 are known causal genes for HCM. Here we generated two human-induced pluripotent stem cell lines from two HCM patients carrying two heterozygous mutations in MYBPC3 (c.459delC) and PRKAG2 (c.1703C > T). Both iPSC lines expressed pluripotent markers, had a normal karyotype, and were able to differentiate into three germ layers, making them potentially valuable tools for modeling HCM in vitro and investigating the pathological mechanisms related to these two variants.

    View details for DOI 10.1016/j.scr.2022.102774

    View details for PubMedID 35413566

  • Cardiac reprogramming via chromatin remodeling by CRISPR activation. Molecular therapy : the journal of the American Society of Gene Therapy Jahng, J. W., Wu, J. C. 1800

    View details for DOI 10.1016/j.ymthe.2021.12.005

    View details for PubMedID 34895515

  • Generation of three induced pluripotent stem cell lines (SCVIi014-A, SCVIi015-A, and SCVIi016-A) from patients with LQT1 caused by heterozygous mutations in the KCNQ1 gene. Stem cell research Zhang, H., Jahng, J. W., Liu, Y., Chase, A. J., Perez, M. V., Wu, J. C. 2021; 55: 102492

    Abstract

    Congenital long QT syndrome type 1 (LQT1) results from KCNQ1 mutations that cause loss of Kv7.1 channel function, leading to arrhythmias, syncope, and sudden cardiac death. Here, we generated three human-induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of LQT1 patients carrying pathogenic variants (c.569 G>A, c.585delG, and c.573_577delGCGCT) in KCNQ1. All lines show typical iPSC morphology, high expression of pluripotent markers, normal karyotype, and are able to differentiate into three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of LQT1 caused by KCNQ1 mutations.

    View details for DOI 10.1016/j.scr.2021.102492

    View details for PubMedID 34411974

  • Generation of three induced pluripotent stem cell lines from hypertrophic cardiomyopathy patients carrying MYH7 mutations. Stem cell research Cao, X., Jahng, J. W., Lee, C., Zha, Y., Wheeler, M. T., Sallam, K., Wu, J. C. 2021; 55: 102455

    Abstract

    MYH7 heterozygous mutations are common genetic causes of hypertrophic cardiomyopathy (HCM). HCM is characterized by hypertrophy of the left ventricle and diastolic dysfunction. We generated three human induced pluripotent stem cell (iPSC) lines from three HCM patients each carrying a single heterozygous mutation in MYH7, c.2167C>T, c.4066G>A, and c.5135G>A, respectively. All lines expressed high levels of pluripotent markers, had normal karyotype, and possessed capability of differentiation into derivatives of the three germ layers, which can serve as valuable tools for modeling HCM in vitro and investigating the pathological mechanisms related to MYH7 mutations.

    View details for DOI 10.1016/j.scr.2021.102455

    View details for PubMedID 34352619

  • The role of metabolism in directed differentiation versus trans-differentiation of cardiomyocytes. Seminars in cell & developmental biology Jahng, J. W., Zhang, M., Wu, J. C. 2021

    Abstract

    The advent of induced pluripotent stem cells (iPSCs) and identification of transcription factors for cardiac reprogramming have raised hope to cure heart disease, the leading cause of death in the world. Our knowledge in heart development and molecular barriers of cardiac reprogramming is advancing, but many hurdles are yet to be overcome for clinical translation. Importantly, we lack a full understanding of molecular mechanisms governing cell fate conversion toward cardiomyocytes. In this review, we will discuss the role of metabolism in directed differentiation versus trans-differentiation of cardiomyocytes. Cardiomyocytes exhibit a unique metabolic feature distinct from PSCs and cardiac fibroblasts, and there are multiple overlapping molecular mechanisms underlying metabolic reprogramming during cardiomyogenesis. We will discuss key metabolic changes occurring during cardiomyocytes differentiation from PSCs and cardiac fibroblasts, and the potential role of metabolic reprogramming in the enhancement strategies for cardiomyogenesis. Only when such details are discovered will more effective strategies to enhance the de novo production of cardiomyocytes be possible.

    View details for DOI 10.1016/j.semcdb.2021.05.018

    View details for PubMedID 34074592

  • Generation of three heterozygous KCNH2 mutation-carrying human induced pluripotent stem cell lines for modeling LQT2 syndrome. Stem cell research Mondejar-Parreno, G., Jahng, J. W., Belbachir, N., Wu, B. C., Zhang, X., Perez, M. V., Badhwar, N., Wu, J. C. 2021; 54: 102402

    Abstract

    Congenital long QT syndrome type 2 (LQT2) results from KCNH2 mutations that cause loss of Kv11.1 channel function which can lead to arrhythmias, syncope, and sudden death. Here, we generated three human-induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of two LQT2 patients carrying pathogenic variants (c.1714G>A and c.2960del) and one LQT2 patient carrying a variant of uncertain significance (c.1870A>T) in KCNH2. All lines show typical iPSC morphology, high expression of pluripotent markers, normal karyotype, and differentiate into three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of LQTS caused by caused by KCNH2 mutations.

    View details for DOI 10.1016/j.scr.2021.102402

    View details for PubMedID 34051449

  • Generation of three induced pluripotent stem cell lines, SCVIi003-A, SCVIi004-A, SCVIi005-A, from patients with ARVD/C caused by heterozygous mutations in the PKP2 gene. Stem cell research Jahng, J. W., Black, K. E., Liu, L., Bae, H. R., Perez, M., Ashley, E. A., Sallam, K., Wu, J. C. 2021; 53: 102284

    Abstract

    Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease which can cause life-threatening ventricular arrhythmias and cardiac dysfunction. The autosomal dominant form of ARVD/C is caused by mutations in the cardiac desmosome, such as those in the plakoglobin plakophilin-2 (PKP2) gene. Here, we generated three human induced pluripotent stem cell (iPSC) lines from the peripheral blood mononuclear cells (PBMCs) of three ARVD/C patients carrying pathogenic variants in their PKP2 genes (c.2065_2070delinsG; c.235C>T; c.1725_1728dup). All lines show the typical morphology of pluripotent stem cells, demonstrate high expression of pluripotent markers, display normal karyotype, and differentiate into all three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of ARVD/C caused by PKP2 mutation.

    View details for DOI 10.1016/j.scr.2021.102284

    View details for PubMedID 33743362

  • Generation of two heterozygous MYBPC3 mutation-carrying human iPSC lines, SCVIi001-A and SCVIi002-A, for modeling hypertrophic cardiomyopathy. Stem cell research Liu, L., Shenoy, S. P., Jahng, J. W., Liu, Y., Knowles, J. W., Zhuge, Y., Wu, J. C. 2021; 53: 102279

    Abstract

    Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can cause sudden cardiac death and heart failure. HCM often arises from mutations in sarcomeric genes, among which the MYBPC3 is the most frequently mutated. Here we generated two human induced pluripotent stem cell (iPSC) lines from a HCM patient who has a familial history of HCM and his daughter who carries the pathogenic non-coding mutation. All lines show the typical morphology of pluripotent cells, a high expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers. These lines provide a valuable resource for studying the molecular basis of HCM and drug screening for HCM.

    View details for DOI 10.1016/j.scr.2021.102279

    View details for PubMedID 33743363

  • Tumor Repressor Circular RNA as a New Target for Preventative Gene Therapy Against Doxorubicin-Induced Cardiotoxicity. Circulation research Jahng, J. W., Liu, L. n., Wu, J. C. 2020; 127 (4): 483–85

    View details for DOI 10.1161/CIRCRESAHA.120.317568

    View details for PubMedID 32762533