Lorenzo R. Sewanan
A5077550823- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- COVID-19 Clinical Research Studies
- Cardiovascular Function and Risk Factors
- Electrospun Nanofibers in Biomedical Applications
- SARS-CoV-2 and COVID-19 Research
- Cardiac Structural Anomalies and Repair
- Long-Term Effects of COVID-19
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- COVID-19 diagnosis using AI
- Cardiac electrophysiology and arrhythmias
- SARS-CoV-2 detection and testing
- Muscle Physiology and Disorders
- Pluripotent Stem Cells Research
- Transplantation: Methods and Outcomes
- 3D Printing in Biomedical Research
- Mechanical Circulatory Support Devices
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Cell death mechanisms and regulation
- Viral Infections and Immunology Research
- Renal Transplantation Outcomes and Treatments
- Dental Research and COVID-19
- Cardiovascular Disease and Adiposity
Yale University
2016-2024
Columbia University Irving Medical Center
2022-2024
Columbia University
2021-2024
New York Hospital Queens
2022-2023
NewYork–Presbyterian Hospital
2022-2023
There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than women1–5. However, whether immune responses against acute respiratory syndrome (SARS-CoV-2) differ between sexes, such differences correlate with the sex difference in course of COVID-19, currently unknown. Here we examined viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines blood-cell phenotyping patients moderate COVID-19 who had not...
Abstract Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard diagnosis real-time RT-PCR detection of from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, global shortages swabs personal protective equipment, however, necessitate validation new approaches. Saliva a promising candidate diagnostics because (1) collection minimally invasive can reliably be self-administered (2) saliva...
Abstract Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that dysbiosis is translocation of bacteria into blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces mice, which correlated alterations to Paneth cells and goblet cells, markers barrier permeability. Samples collected from 96 patients at two...
Abstract We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections porcine were into ribbon-like shapes, mounted in specialized clips for seeding culture. Scaffolds first tested by with neonatal rat ventricular myocytes. EHTs beat synchronously day five exhibited robust...
Hypertrophic cardiomyopathy (HCM) is often caused by single sarcomeric gene mutations that affect muscle contraction. Pharmacological correction of mutation effects prevents but does not reverse disease in mouse models. Suspecting diseased extracellular matrix to blame, we obtained myocardium from a miniature swine model HCM, decellularized thin slices the tissue, and re-seeded them with healthy human induced pluripotent stem cell–derived cardiomyocytes. Compared cardiomyocytes grown on...
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide development effective vaccines therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they not readily adaptable diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a...
Background: Familial hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and typically caused by mutations in genes encoding sarcomeric proteins that regulate contractility. HCM manifestations include left ventricular hypertrophy heart failure, arrythmias, sudden death. How dysregulated force production sensed leads to pathological remodeling remains poorly understood HCM, thereby inhibiting efficient development of new therapeutics. Methods: Our discovery was...
The extent to which health care systems have adapted the COVID-19 pandemic provide necessary cardiac diagnostic services is unknown. aim of this study was determine impact on testing practices, volumes and types services, perceived psychological stress providers worldwide. International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular at pandemic's onset 1 year later. Multivariable regression used factors associated with procedure volume...
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have wide potential application in basic research, drug discovery, and regenerative medicine, but functional maturation remains challenging. Here, we present a method whereby of hiPSC-CMs can be accelerated by simultaneous physiological Ca2+ frequency-ramped electrical pacing culture. This combination produces positive force-frequency behavior, twitch kinetics, robust β-adrenergic response, improved handling, cardiac...
Abstract The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although is highly expressed in cancer cells, insufficient cell surface expression desensitizes cells to Fas-induced apoptosis. Here, we show that the increase microaggregate formation on plasma membrane response inhibition of endocytosis sensitizes We used a clinically accessible Rho-kinase inhibitor, fasudil, reduces dynamics by increasing tension. In combination with exogenous soluble...
Significance Chilblain diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and been attributed to viral infection a subsequent robust antiviral immune response. As result, providers managed these cases differently than idiopathic chilblains, which are associated with cold exposure. The relationship between chilblains SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for SARS-CoV-2–specific PCR or...
Hypertrophic cardiomyopathy (HCM) is an inherited disorder caused primarily by mutations to thick and thinfilament proteins. Although thin filament are less prevalent than their oft-studied counterparts, they frequently associated with severe patient phenotypes can offer important insight into fundamental disease mechanisms. We have performed a detailed study of tropomyosin (TPM1) E192K, variant uncertain significance HCM. Molecular dynamics revealed that E192K results in more flexible TPM1...
Point mutations to the human gene TPM1 have been implicated in development of both hypertrophic and dilated cardiomyopathies. Such observations led studies investigating link between single residue changes biophysical behavior tropomyosin molecule. However, degree which these molecular perturbations explain performance intact sarcomeres containing mutant remains uncertain. Here, we present a modeling approach that integrates various aspects tropomyosin's properties into cohesive paradigm...