A5068156554- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Muscle activation and electromyography studies
- Muscle Physiology and Disorders
- Cardiovascular Effects of Exercise
- Ion Channels and Receptors
- Biochemical Analysis and Sensing Techniques
- Pulmonary Hypertension Research and Treatments
- Cardiac Structural Anomalies and Repair
- Cardiac electrophysiology and arrhythmias
- Heart Failure Treatment and Management
- Neuroscience of respiration and sleep
- Metabolism, Diabetes, and Cancer
- Olfactory and Sensory Function Studies
- Cellular Mechanics and Interactions
- Heart Rate Variability and Autonomic Control
- Fuel Cells and Related Materials
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Neurobiology and Insect Physiology Research
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced MRI Techniques and Applications
- Adipose Tissue and Metabolism
- Acute Myocardial Infarction Research
Johns Hopkins University
2022-2025
Johns Hopkins Medicine
2022-2024
Washington State University
2014-2021
Washington Center
2019-2021
Previous studies aimed at defining the mechanistic basis of hypertrophic cardiomyopathy caused by A331P cardiac actin have reported conflicting results. The mutation is located along an surface strand, proximal to residues that interact with tropomyosin. These F-actin-tropomyosin associations are vital for proper contractile inhibition. To help resolve disease pathogenesis, we implemented a multidisciplinary approach. Transgenic Drosophila, expressing actin, displayed skeletal muscle...
Muscles produce force and power by utilizing chemical energy through ATP hydrolysis. During concentric contractions (shortening), muscles generate less compared to isometric contractions, but consume greater amounts of as shortening velocity increases. Conversely, more is generated consumed during eccentric muscle (lengthening). This relationship between force, use, the contraction has important implications for understanding efficiency, molecular mechanisms underlying this behavior remain...
In the brainstem nucleus of solitary tract (NTS), primary vagal afferent neurons express transient receptor potential vanilloid subfamily member 1 (TRPV1) at their central terminals where it contributes to quantal forms glutamate release. The endogenous membrane lipid anandamide (AEA) is a putative TRPV1 agonist in brain, yet extent which AEA activation has neurophysiological consequence not well established. We investigated ability activate comparison capsaicin (CAP). Using ratiometric...
Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure reduced ejection fraction pulmonary hypertension (HFrEF-PH). However, such often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize depression HFrEF-PH, identify those components reflected uncover biophysical mechanisms.
Vagal afferent signaling coordinates autonomic reflex function and informs associated behaviors. Thermosensitive transient receptor potential (TRP) channels detect temperature nociceptive stimuli in somatosensory neurons, however their role vagal remains less well understood. We report that the TRPM3 ion channel provides a major thermosensitive point of control over synaptic transmission. conclude translates physiological changes to neurophysiological outputs can serve as cellular integrator...
Cranial visceral afferents contained within the solitary tract (ST) contact second-order neurons in nucleus of (NTS) and release excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, spontaneous release. The presence TRPV1 central terminals a majority ST conveys activity-dependent asynchronous provides temperature sensitive calcium conductance which largely determines rate vesicle fusion. is present unmyelinated C-fiber these facilitated forms may...
Muscle contraction results from force-generating cross-bridge interactions between myosin and actin. Cross-bridge cycling kinetics underlie fundamental contractile properties, such as active force production energy utilization. Factors that influence at the molecular level propagate through sarcomeres, cells tissue to modulate whole-muscle function. Conversely, movement changes in muscle length can on level. Reduced, single-molecule single-fibre experiments have shown increasing strain...
Introduction: Cardiac troponin I (cTnI, TNNI3 gene) is a highly conserved subunit of the sarcomere that inhibits contraction by preventing actin-myosin interaction. Pathogenic variants can cause both hypertrophic and restrictive cardiomyopathies but lack targeted therapies. We identified family with cardiomyopathy carrying cTnI variant at amino acid 157 (A157V). Using CRISPR-Cas9, we generated knock-in mouse model reflecting this mutation (A158V in mouse). Our previous studies showed...
Limb-girdle muscular dystrophy 2i (LGMD2i) is a dystroglycanopathy that compromises myofiber integrity and primarily reduces power output in limb muscles but can influence cardiac muscle as well. Previous studies of LGMD2i made use transgenic mouse model which proline-to-leucine (P448L) mutation fukutin-related protein severely glycosylation α-dystroglycan. Muscle function compromised P448L mice manner similar to human patients with LGMD2i. In situ reported lower maximal twitch force...
Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in heart failure patients with reduced ejection fraction pulmonary hypertension (HFrEF-PH). However, such often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction.To determine components depression HFrEF-PH, identify those reflected elucidate their biophysical mechanisms.Resting, calcium- load-dependent mechanics were measured...
Heart failure with preserved ejection fraction (HFpEF) has few effective therapies yet exacts substantial mortality. Its multi-system nature made animal modeling difficult, but recent efforts combining diet-induced obesity and hemodynamic stress are popular: mouse - L-NAME/high-fat diet (HFD) ovariectomized (OVX) females HFD-induced obesity/cardiac pressure overload (PO) (HFD+OVX+PO), ZSF1 rat, obese/hypertensive Göttingen minipigs. We reported human HFpEF myocyte defects including reduced...