- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Ion Channels and Receptors
- Neuroscience and Neuropharmacology Research
- Cardiac Ischemia and Reperfusion
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Redox biology and oxidative stress
- Sleep and Wakefulness Research
- Chemotherapy-induced cardiotoxicity and mitigation
- Diamond and Carbon-based Materials Research
- Electrochemical Analysis and Applications
- Diabetes Treatment and Management
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Advanced Fluorescence Microscopy Techniques
- Heart Failure Treatment and Management
- Cardiomyopathy and Myosin Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Signaling Pathways in Disease
- Cancer, Hypoxia, and Metabolism
- Hemoglobin structure and function
- ATP Synthase and ATPases Research
Columbia University
2019-2024
Columbia University Irving Medical Center
2022-2024
Physiologie et Médecine Expérimentale du Coeur et des Muscles
2017-2020
Inserm
2015-2020
Centre National de la Recherche Scientifique
2017
Université de Montpellier
2017
Hôpital Arnaud de Villeneuve
2015
Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute irreversible cardiotoxicity. Currently, there no method predict the future development of HF these patients. In order identify early biomarkers anthracycline cardiotoxicity long-term survivors childhood cancer, this longitudinal study aimed analyze late in-vivo regional myocardial anthracycline-induced...
The Ca2+-binding protein calmodulin has emerged as a pivotal player in tuning Na+ channel function, although its impact vivo remains to be resolved. Here, we identify the role of and NaV1.5 interactome regulating late current cardiomyocytes. We created transgenic mice with cardiac-specific expression human channels alanine substitutions for IQ motif (IQ/AA). mutations rendered incapable binding C-terminus. IQ/AA exhibited normal ventricular repolarization without arrhythmias an absence...
Significance Calmodulin (CaM) regulation of cardiac Na V channels is vital for physiology and pathophysiology. Channelopathic mutations in 1.5 that disrupt CaM binding trigger two mechanistically divergent arrhythmia syndromes. Specifically, long QT syndrome 3 results from a gain-of-channel function, while Brugada stems loss-of-channel function. Yet, mechanisms elicit seemingly paradoxical changes channel function are unknown. Using single-channel analysis, we demonstrate the disruption to...
NEDD4L is a HECT-type E3 ligase that catalyzes the addition of ubiquitin to intracellular substrates such as cardiac voltage-gated sodium channel, NaV1.5. The intramolecular interactions regulate its enzymatic activity which essential for proteostasis. For NaV1.5, this process critical alterations in Na+ current involved diseases including arrhythmias and heart failure. In study, we perform extensive biochemical functional analyses implicate C2 domain first WW-linker (1,2-linker)...
Calmodulin (CaM) regulation of voltage-gated calcium (CaV1-2) channels is a powerful Ca2+-feedback mechanism to adjust channel activity in response Ca2+ influx. Despite progress resolving mechanisms CaM-CaV feedback, the stoichiometry CaM interaction with CaV remains ambiguous. Functional studies that tethered CaV1.2 suggested single sufficed for yet biochemical, FRET, and structural showed multiple molecules interact distinct interfaces within cytosolic segments, suggesting functional may...