Publications by authors named "Paul D Pang"
Transcriptomic Profiling of Human Myocardium at Sudden Death to Define Vulnerable Substrate for Lethal Arrhythmias.
JACC Clin Electrophysiol
January 2025
Background: While some chronic pathological substrates for sudden cardiac death (SCD) are well known (eg, coronary artery disease and left ventricular [LV] dysfunction), the acute vulnerable myocardial state predisposing to fatal arrhythmia remains a critical barrier to near-term SCD prevention.
Objectives: This study sought to define the distinct myocardial transcriptomic profile of autopsy-defined arrhythmic sudden deaths, compared to nonarrhythmic sudden deaths and trauma deaths, to determine the acute vulnerable state in the hours to days before SCD.
Methods: We used autopsy to adjudicate arrhythmic from nonarrhythmic causes in 1,265 sudden deaths in San Francisco County from 2011 to 2018.
Tackling the challenges of new approach methods for predicting drug effects from model systems.
Nat Rev Drug Discov
August 2024
Article Synopsis
- The FDA Modernization Act 2.0, passed in 2022, encourages the use of new methods to evaluate how drug candidates affect humans.
- Researchers are focusing on microphysiological systems, which use human-derived induced pluripotent stem cells, to predict drug effects more accurately.
- Progress includes addressing challenges in this field and leveraging artificial intelligence tools for better data analysis and predictions.
Article Synopsis
- Hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN) is caused by mutations in the TTR gene, leading to health complications.
- The study created two induced pluripotent stem cell (iPSC) lines from ATTR-PN patients with specific TTR mutations, which showed normal cell characteristics and the ability to differentiate into various cell types.
- These iPSC lines are important for studying ATTR-PN's mechanisms and developing patient-specific models for better understanding and potential treatments.
Spinal muscular atrophy (SMA) is a severe neurodegenerative muscular disease caused by the homozygous loss of survival of motor neuron 1 (SMN1) genes. SMA patients exhibit marked skeletal muscle (SKM) loss, eventually leading to death. Here we generated two iPSC lines from two SMA type I patients with homozygous SMN1 mutations and validated the pluripotency and the ability to differentiate into three germ layers.
View Article and Find Full Text PDFTreating Duchenne Muscular Dystrophy: The Promise of Stem Cells, Artificial Intelligence, and Multi-Omics.
Front Cardiovasc Med
March 2022
Article Synopsis
- * Current treatments are limited, but there are three major advances on the horizon: human induced pluripotent stem cells (iPSCs) for personalized therapies, artificial intelligence (AI) to analyze vast data and uncover molecular mechanisms, and comprehensive disease models utilizing multi-omics data to guide precision medicine.
- * These innovations aim to not only slow down muscle degeneration but potentially regenerate healthy muscle tissue, potentially transforming treatment approaches for disorders like DMD.
Ischemia due to hypoperfusion is one of the most common forms of acute kidney injury. We hypothesized that kidney hypoxia initiates the up-regulation of miR-218 expression in endothelial progenitor cells (EPCs) to guide endocapillary repair. Murine renal artery-derived EPCs (CD34/CD105) showed down-regulation of mmu-Mir218-5p/U6 RNA ratio after ischemic injury, while in human renal arteries, MIR218-5p expression was up-regulated after ischemic injury.
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- Leukemia stem cells have a unique ability to sustain and initiate leukemia, and the role of Krüppel-like factor 4 (KLF4) in this process is linked to its promotion of disease progression in chronic myeloid leukemia (CML).
- The deletion of the Klf4 gene in a mouse model significantly impacted the survival and self-renewal of leukemia cells, indicating that KLF4 is crucial for maintaining CML.
- KLF4 represses the Dyrk2 gene, and its loss leads to higher levels of DYRK2, which inhibit cell survival and self-renewal through the modulation of crucial proteins like c-Myc and p53, presenting a potential target for new treatments.
Background The sodium channel, Na1.5, encoded by SCN 5A, undergoes developmentally regulated splicing from inclusion of exon 6A in the fetal heart to exon 6B in adults. These mutually exclusive exons differ in 7 amino acids altering the electrophysiological properties of the Na1.
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