Scholars@Duke
Jonathan Andrew Stiber

Jonathan Andrew Stiber

Professor of Medicine
Medicine, Cardiology
stibe001@mc.duke.edu
Duke Box 102144, Durham, NC 27710
Dept of Medicine, Durham, NC

Selected Publications

Drebrin is Required for Myosin-facilitated Actin Cytoskeletal Remodeling during Pulmonary Alveolar Development.

Journal Article Am J Respir Cell Mol Biol · April 2024 Alveolar septation increases gas-exchange surface area and requires coordinated cytoskeletal rearrangement in lung fibroblasts (LFs) to balance the demands of contraction and cell migration. We hypothesized that DBN (drebrin), a modulator of the actin cyto ... Full text Link to item Cite

Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation.

Journal Article J Biol Chem · July 2023 Reversible lysine-63 (K63) polyubiquitination regulates proinflammatory signaling in vascular smooth muscle cells (SMCs) and plays an integral role in atherosclerosis. Ubiquitin-specific peptidase 20 (USP20) reduces NFκB activation triggered by proinflamma ... Full text Open Access Link to item Cite

STIM1 interacts with HCN4 channels to coordinate diastolic depolarization in the mouse Sinoatrial node.

Journal Article bioRxiv · May 3, 2023 Cardiomyocytes in the sinoatrial node (SAN) are specialized to undergo spontaneous diastolic depolarization (DD) to create action potentials (AP) that serve as the origin of the heartbeat. Two cellular clocks govern DD: the membrane clock where ion channel ... Full text Link to item Cite

Drebrin attenuates atherosclerosis by limiting smooth muscle cell transdifferentiation.

Journal Article Cardiovasc Res · February 21, 2022 AIMS: The F-actin-binding protein Drebrin inhibits smooth muscle cell (SMC) migration, proliferation, and pro-inflammatory signalling. Therefore, we tested the hypothesis that Drebrin constrains atherosclerosis. METHODS AND RESULTS: SM22-Cre+/Dbnflox/flox/ ... Full text Open Access Link to item Cite

Drebrin, an actin-binding protein, is required for lens morphogenesis and growth.

Journal Article Dev Dyn · November 2021 BACKGROUND: Lens morphogenesis, architecture, and clarity are known to be critically dependent on actin cytoskeleton organization and cell adhesive interactions. There is limited knowledge, however regarding the identity and role of key proteins regulating ... Full text Link to item Cite

Actin-binding protein, Drebrin, is required for mouse lens morphogenesis and growth

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2020 Cite

RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome.

Journal Article Nat Commun · January 10, 2019 The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the ... Full text Link to item Cite

Real-world implications of QT prolongation in patients receiving voriconazole and amiodarone.

Journal Article J Antimicrob Chemother · January 1, 2019 OBJECTIVES: Voriconazole, a triazole antifungal, is frequently prescribed in a complex patient population with comorbidities that require concomitant administration of QT interval-prolonging medications. We sought to evaluate QT interval prolongation in pa ... Full text Link to item Cite

Drebrin regulates angiotensin II-induced aortic remodelling.

Journal Article Cardiovasc Res · November 1, 2018 AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebr ... Full text Open Access Link to item Cite

USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

Journal Article Arterioscler Thromb Vasc Biol · October 2018 Objective- Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination that activates proteins downstream of proatherogenic receptors. Deubiquitination of these prote ... Full text Link to item Cite

Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.

Journal Article JCI Insight · September 7, 2017 The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic receptor (βAR) signaling and endocytosis. Previous studies showed that cardi ... Full text Open Access Link to item Cite

Sinus Node Dysfunction and Atrial Fibrillation: A Reversible Phenomenon?

Journal Article Pacing Clin Electrophysiol · April 2017 BACKGROUND: Symptomatic sinus node dysfunction (SND) consists of a variety of manifestations, including tachycardia-bradycardia syndrome. Atrial fibrillation (AF) is commonly associated with SND, which complicates the management of both conditions. This pa ... Full text Link to item Cite

Crizotinib Inhibits Hyperpolarization-activated Cyclic Nucleotide-Gated Channel 4 Activity.

Journal Article Cardiooncology · 2017 BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether ... Full text Open Access Link to item Cite

The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.

Journal Article Arterioscler Thromb Vasc Biol · May 2016 OBJECTIVE: Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfami ... Full text Open Access Link to item Cite

STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node.

Conference Proc Natl Acad Sci U S A · October 13, 2015 Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on the membrane surface (membrane clock) with rhythmic Ca(2+) release from internal Ca(2+) s ... Full text Link to item Cite

Skeletal muscle store-operated Ca2+ entry and STIM/Orai signaling in skeletal muscle

Chapter · November 1, 2013 In skeletal muscle, Ca2+ release from intracellular stores triggers actomyosin cross-bridge formation to generate and modulate contractile force, but myocytes also use Ca2+ signaling as a way to sense and respond to changes in workload to alter gene expres ... Full text Cite

Heart rate decrease during crizotinib treatment and potential correlation to clinical response.

Journal Article Cancer · June 1, 2013 BACKGROUND: Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB ... Full text Link to item Cite

Cytoskeletal regulation of TRPC channels in the cardiorenal system.

Journal Article Curr Hypertens Rep · December 2012 Transient receptor potential canonical (TRPC) channels have been implicated in several aspects of cardiorenal physiology including regulation of blood pressure, vasoreactivity, vascular remodeling, and glomerular filtration. Gain and loss of function studi ... Full text Link to item Cite

Dynamic regulation of sarcoplasmic reticulum Ca(2+) stores by stromal interaction molecule 1 and sarcolipin during muscle differentiation.

Journal Article Dev Dyn · April 2012 During muscle development, the sarco/endoplasmic reticulum (SR/ER) undergoes remodeling to establish a specialized internal Ca(2+) store for muscle contraction. We hypothesized that store operated Ca(2+) entry (SOCE) is required to fill Ca(2+) stores and i ... Full text Link to item Cite

Asymptomatic profound sinus bradycardia (heart rate ≤45) in non-small cell lung cancer patients treated with crizotinib.

Journal Article J Thorac Oncol · December 2011 Crizotinib, a dual MET/ALK inhibitor, is now in advanced clinical development for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We have observed several patients who developed profound but asymptomatic sin ... Full text Link to item Cite

The role of store-operated calcium influx in skeletal muscle signaling.

Journal Article Cell Calcium · May 2011 In cardiac and skeletal muscle Ca(2+) release from intracellular stores triggers actomyosin cross-bridge formation and the generation of contractile force. In the face of large fluctuations of intracellular calcium ([Ca(2+)](i)) that occur with contractile ... Full text Link to item Cite

Effect of oxidative stress on homer scaffolding proteins.

Journal Article PLoS One · 2011 Homer proteins are a family of multifaceted scaffolding proteins that participate in the organization of signaling complexes at the post-synaptic density and in a variety of tissues including striated muscle. Homer isoforms form multimers via their C-termi ... Full text Link to item Cite

TRPC1 channels are critical for hypertrophic signaling in the heart.

Journal Article Circ Res · November 6, 2009 RATIONALE: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein-coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel acti ... Full text Link to item Cite

Mechanosensitive channels in striated muscle and the cardiovascular system: not quite a stretch anymore.

Journal Article J Cardiovasc Pharmacol · August 2009 Stretch-activated or mechanosensitive channels transduce mechanical forces into ion fluxes across the cell membrane. These channels have been implicated in several aspects of cardiovascular physiology including regulation of blood pressure, vasoreactivity, ... Full text Link to item Cite

STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle.

Journal Article Nat Cell Biol · June 2008 It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known ab ... Full text Link to item Cite

Mice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity.

Journal Article Mol Cell Biol · April 2008 Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play ... Full text Link to item Cite

Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes.

Journal Article Proc Natl Acad Sci U S A · October 31, 2006 The G protein-coupled receptor kinases (GRKs) and beta-arrestins, families of molecules essential to the desensitization of G protein-dependent signaling via seven-transmembrane receptors (7TMRs), have been recently shown to also transduce G protein-indepe ... Full text Link to item Cite

Excitation-contraction coupling in airway smooth muscle.

Journal Article J Biol Chem · October 6, 2006 Excitation-contraction (EC) coupling in striated muscles is mediated by the cardiac or skeletal muscle isoform of voltage-dependent L-type Ca(2+) channel (Ca(v)1.2 and Ca(v)1.1, respectively) that senses a depolarization of the cell membrane, and in respon ... Full text Link to item Cite

Homer modulates NFAT-dependent signaling during muscle differentiation.

Journal Article Dev Biol · November 15, 2005 While changes in intracellular calcium are well known to influence muscle contraction through excitation contraction coupling, little is understood of the calcium signaling events regulating gene expression through the calcineurin/NFAT pathway in muscle. H ... Full text Link to item Cite

Ryanodine receptors in muscarinic receptor-mediated bronchoconstriction.

Journal Article J Biol Chem · July 15, 2005 Ryanodine receptors (RyRs), intracellular calcium release channels essential for skeletal and cardiac muscle contraction, are also expressed in various types of smooth muscle cells. In particular, recent studies have suggested that in airway smooth muscle ... Full text Link to item Cite

TRPC3 channels confer cellular memory of recent neuromuscular activity.

Journal Article Proc Natl Acad Sci U S A · June 22, 2004 Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties of contraction, metabolism, and muscle mass to changing work demands (muscle plasticity). Calcineurin, a calcium/calmod ... Full text Link to item Cite

Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris.

Journal Article Am J Cardiol · June 15, 2000 We sought to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of basic fibroblast growth factor (bFGF), administered as a single intracoronary injection, to subjects with stable angina pectoris secondary to coronary artery disease. bFG ... Full text Link to item Cite

Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dogs.

Journal Article J Am Coll Cardiol · February 2000 OBJECTIVE: In preparation for clinical trials of basic fibroblast growth factor (bFGF) to treat ischemic heart disease, we sought to identify a clinically feasible method of bFGF administration. BACKGROUND: Basic FGF has been shown to promote collateral de ... Full text Link to item Cite

Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis.

Journal Article Cardiovasc Res · November 1999 OBJECTIVE: Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to ... Full text Link to item Cite

Pharmacodynamics of basic fibroblast growth factor: route of administration determines myocardial and systemic distribution.

Journal Article Cardiovasc Res · October 1997 OBJECTIVE: We have shown that basic fibroblast growth factor (bFGF/FGF-2) enhances myocardial collateral development in a canine model of progressive coronary occlusion when delivered via the left atrial or intracoronary routes; however, we have found intr ... Full text Link to item Cite

Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels.

Journal Article J Am Coll Cardiol · April 1997 OBJECTIVES: We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF tr ... Full text Link to item Cite

Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.

Journal Article Circulation · September 1, 1996 BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of m ... Full text Link to item Cite

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

Journal Article Circulation · January 1, 1995 BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The ... Full text Link to item Cite