All Publications

  • Management of a Chronically Infolded Self-Expanding Aortic Valve. JACC. Case reports Hu, S., Amponsah, D., Malik, S., Nguyen, P., Mantri, N., Elorbany, R., Watkins, A. C., Lin, Y., Kang, G. 2026: 107362

    Abstract

    Infolding is a known complication of self-expandable transcatheter valves that typically causes hemodynamic compromise. Delayed diagnosis of infolding is rare and can result in premature leaflet degeneration, with limited treatment options.A 71-year-old man presented 5 years after transcatheter aortic valve replacement (TAVR) with severe intravalvular regurgitation. Transesophageal echocardiography revealed significant infolding of the valve. The patient underwent valve-in-valve TAVR, which successfully resolved the aortic insufficiency.This is the first reported case of a chronically infolded TAVR, which is a rare but significant complication of self-expandable valves. We demonstrate that valve-in-valve replacement can successfully overcome chronic frame distortion and endothelialization.Transcatheter valve infolding does not necessarily cause significant hemodynamic changes, which can lead to delays in diagnosis and treatment. Chronic infolding can be visualized by 3D computed tomography and can result in premature leaflet degeneration. Structural distortion of self-expandable valves, even years after implant, can be overcome with high-pressure valvuloplasty and valve-in-valve replacement.

    View details for DOI 10.1016/j.jaccas.2026.107362

    View details for PubMedID 41811287

  • A New Era of Cardiothoracic Transplantation in Adults With Congenital Heart Disease. Journal of the American Heart Association Hu, S., Krishnan, A., Mullis, D. M., Heng, E., Elde, S., Garrison, A. C., Alnasir, D., Berg, A. R., Vargas, N. M., Haeffele, C., Lui, G., Woo, Y. J., MacArthur, J. W. 2026: e045279

    Abstract

    A growing number of children with congenital heart disease survive to adulthood and require heart transplantation. This study evaluates the trends and outcomes of cardiothoracic transplantation for patients with adult congenital heart disease (ACHD) and describes our institution's 3 decades of experience.We identified all patients with ACHD who underwent first-time cardiothoracic transplantation at our institution between December 1987 and December 2024. We compared characteristics and outcomes between a historical and contemporary cohort of transplant recipients.In total, 196 patients with ACHD underwent cardiothoracic transplantation. The annual rate of cardiothoracic transplantation in patients with ACHD doubled after 2018. The first era of heart transplantation in patients with ACHD from 1987 to 2018 is defined predominantly by heart-lung transplantation, most commonly for isolated septal defect. The second era since 2018 is defined by sicker, more complex patients. Following the United Network for Organ Sharing heart allocation policy change, recipients were older, underwent more prior cardiac surgeries, were more likely to be hospitalized, and were more likely to have single-ventricle anatomy with Glenn/Fontan palliation. Comparing the 2 eras, 1-year survival rates for all patients with ACHD were comparable (81% versus 81%, P=0.939) and improved for heart-only transplant recipients (72.5% versus 90.7%, P=0.066).The number and complexity of patients with ACHD undergoing cardiothoracic transplantation has grown, with a significant increase in patients who previously underwent palliative surgeries. With increased use of medical and surgical adjuncts, excellent long-term survival for transplant recipients is achievable.

    View details for DOI 10.1161/JAHA.125.045279

    View details for PubMedID 41804900

  • Growing Use, Evolving Risk: A Contemporary Profile of Heart-Liver Transplantation Berg, A., Krishnan, A., Heng, E., Hu, S., Mullis, D., Vargas, N., Vu, A., Garrison, A., Alnasir, D., Clark, D., Haeffele, C., Lui, G., Teuteberg, J., Woo, Y., Macarthur, J. LIPPINCOTT WILLIAMS & WILKINS. 2025

    View details for DOI 10.1161/circ.152.suppl_3.4367893

    View details for Web of Science ID 001613950900034

  • Transcription factor antagonism regulates heterogeneity in embryonic stem cell states MOLECULAR CELL Hu, S., Metcalf, E., Mahat, D., Chan, L., Sohal, N., Chakraborty, M., Hamilton, M., Singh, A., Singh, A., Lees, J. A., Sharp, P. A., Garg, S. 2022; 82 (23): 4410-+

    Abstract

    Gene expression heterogeneity underlies cell states and contributes to developmental robustness. While heterogeneity can arise from stochastic transcriptional processes, the extent to which it is regulated is unclear. Here, we characterize the regulatory program underlying heterogeneity in murine embryonic stem cell (mESC) states. We identify differentially active and transcribed enhancers (DATEs) across states. DATEs regulate differentially expressed genes and are distinguished by co-binding of transcription factors Klf4 and Zfp281. In contrast to other factors that interact in a positive feedback network stabilizing mESC cell-type identity, Klf4 and Zfp281 drive opposing transcriptional and chromatin programs. Abrogation of factor binding to DATEs dampens variation in gene expression, and factor loss alters kinetics of switching between states. These results show antagonism between factors at enhancers results in gene expression heterogeneity and formation of cell states, with implications for the generation of diverse cell types during development.

    View details for DOI 10.1016/j.molcel.2022.10.022

    View details for Web of Science ID 000922730600005

    View details for PubMedID 36356583

    View details for PubMedCentralID PMC9722640

  • Lineages of embryonic stem cells show non-Markovian state transitions ISCIENCE Udomlumleart, T., Hu, S., Garg, S. 2021; 24 (8): 102879

    Abstract

    Pluripotent embryonic stem cells (ESCs) constitute the cell types of the adult vertebrate through a series of developmental state transitions. These states can be defined by expression levels of marker genes, such as Nanog and Sox2. In culture, ESCs reversibly transition between states. However, whether ESCs retain memory of their previous states or transition in a memoryless (Markovian) process remains relatively unknown. Here, we show some highly dynamic lineages of ESCs do not exhibit the Markovian property: their previous states and kin relations influence future choices. Unexpectedly, the distribution of lineages across their composition between states is constant over time, contrasting with the predictions of a Markov model. Additionally, highly dynamic ESC lineages show skewed cell fate distributions after retinoic acid differentiation. Together, these data suggest ESC lineage is an important variable governing future cell states, with implications for stem cell function and development.

    View details for DOI 10.1016/j.isci.2021.102879

    View details for Web of Science ID 000686897200066

    View details for PubMedID 34401663

    View details for PubMedCentralID PMC8353490

  • MicroRNAs organize intrinsic variation into stem cell states PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chakraborty, M., Hu, S., Visness, E., Del Giudice, M., De Martino, A., Bosia, C., Sharp, P. A., Garg, S. 2020; 117 (12): 6942-6950

    Abstract

    Pluripotent embryonic stem cells (ESCs) contain the potential to form a diverse array of cells with distinct gene expression states, namely the cells of the adult vertebrate. Classically, diversity has been attributed to cells sensing their position with respect to external morphogen gradients. However, an alternative is that diversity arises in part from cooption of fluctuations in the gene regulatory network. Here we find ESCs exhibit intrinsic heterogeneity in the absence of external gradients by forming interconverting cell states. States vary in developmental gene expression programs and display distinct activity of microRNAs (miRNAs). Notably, miRNAs act on neighborhoods of pluripotency genes to increase variation of target genes and cell states. Loss of miRNAs that vary across states reduces target variation and delays state transitions, suggesting variable miRNAs organize and propagate variation to promote state transitions. Together these findings provide insight into how a gene regulatory network can coopt variation intrinsic to cell systems to form robust gene expression states. Interactions between intrinsic heterogeneity and environmental signals may help achieve developmental outcomes.

    View details for DOI 10.1073/pnas.1920695117

    View details for Web of Science ID 000521821800084

    View details for PubMedID 32139605

    View details for PubMedCentralID PMC7104302