A5047588489- Mitochondrial Function and Pathology
- Cardiovascular Function and Risk Factors
- Adipose Tissue and Metabolism
- Cardiomyopathy and Myosin Studies
- Metabolism and Genetic Disorders
- Transplantation: Methods and Outcomes
- Hematopoietic Stem Cell Transplantation
- Trace Elements in Health
- Renal Transplantation Outcomes and Treatments
- ATP Synthase and ATPases Research
- Cardiac Fibrosis and Remodeling
- Autophagy in Disease and Therapy
- Peroxisome Proliferator-Activated Receptors
- Cardiac Valve Diseases and Treatments
- Angiogenesis and VEGF in Cancer
- Protein Kinase Regulation and GTPase Signaling
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Cardiac Arrhythmias and Treatments
- Erythropoietin and Anemia Treatment
- Fungal and yeast genetics research
- Heart Failure Treatment and Management
- Biomedical Ethics and Regulation
- Cardiac electrophysiology and arrhythmias
- Adenosine and Purinergic Signaling
Stanford University
2021-2024
Cardiovascular Institute of the South
2022-2024
Boston University
2014-2018
Boston Medical Center
2016
University of Arizona
2009
Background Mitochondrial reactive oxygen species ( ROS ) are associated with metabolic heart disease MHD ). However, the mechanism by which cause is unknown. We tested hypothesis that mitochondrial a key mediator of . Methods and Results Mice fed high‐fat high‐sucrose HFHS diet develop cardiac diastolic dysfunction oxidative posttranslational modifications proteins. Transgenic mice express catalase in mitochondria wild‐type were an or control for 4 months. Cardiac from ‐fed had 3‐fold...
Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats budding yeast fuse to form dicentric chromosome intermediate, which then rearranges translocation other GCRs. next show fusion is general; we found many present the genome also fuse, as does synthetically constructed repeats. Fusion occurs between separated by several kilobases DNA share >20 base...
Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2), react with to form oxidative post-translational modifications, enabling physiological signaling. Cardiac disease and aging associated stress which can impair signaling by altering essential thiolates. We previously found that cardiac-specific overexpression of catalase (Cat), an enzyme detoxifies excess H2O2, protected from delayed cardiac mice. Using proteomics systems...
Despite therapeutic advancements, graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HSCT). In current models GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation microbes expressing pathogen-associated molecular patterns, result in activation host antigen-presenting cells (APCs) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that many pathologic states, results the release...
Myocardial infarction is the leading cause of cardiovascular mortality, with myocardial injury occurring during ischemia and subsequent reperfusion (IR). We previously showed that inhibition protein kinase C delta (δPKC) a pan-inhibitor (δV1-1) mitigates improves mitochondrial function in animal models IR, humans acute infarction, when treated at time opening occluded blood vessel, reperfusion. Cardiac troponin I (cTnI), key sarcomeric cardiomyocyte contraction, phosphorylated by δPKC Here,...
Myocardial hypertrophy and dysfunction are key features of metabolic heart disease due to dietary excess. Metabolic manifests primarily as diastolic but may progress systolic dysfunction, although the mechanism is poorly understood. Liver kinase B1 (LKB1) a activator AMP-activated protein possibly other signaling pathways that oppose myocardial failure. We hypothesized LKB1 essential heart's ability withstand stress
Abstract Cardiac troponin I (cTnI) is a sarcomeric protein critical to myocyte contraction. Unexpectedly, we found that some cTnI localized the mitochondrial matrix in heart, inhibited functions when stably expressed non-cardiac cells and increased opening of permeability transition pore under oxidative stress. Direct, specific, saturable binding ATP synthase was demonstrated vitro , using immune-captured synthase, proximity ligation assay. doubled F 1 0 ATPase activity, whereas skeletal...
Heart transplantation is a life-saving therapy for patients with end-stage heart failure over 4,000 transplants occurring per year. The use of immunosuppression drugs necessary in post to prevent graft rejection. Proliferation signal inhibitors have previously been shown effectively reduce the incidence cardiac allograft vasculopathy (CAV) compared calcineurin but differential mechanisms that drive this benefit and differences vascular profile remain incompletely understood. In study, we...
The scarcity of subspecialist medical expertise, particularly in rare, complex and life-threatening diseases, poses a significant challenge for healthcare delivery. This issue is acute cardiology where timely, accurate management determines outcomes. We explored the potential AMIE (Articulate Medical Intelligence Explorer), large language model (LLM)-based experimental AI system optimized diagnostic dialogue, to potentially augment support clinical decision-making this challenging context....
Abstract Immunosuppressive medications are widely used to treat patients with neoplasms, autoimmune conditions, and solid organ transplants. Prior studies indicate that immunosuppression drugs can cause adverse vascular remodeling. Given the systemic effects of drugs, elucidating cell-type specific drug-effects has been challenging. We utilized induced pluripotent stem-cell derived endothelial cells investigate role on function. found among agents, sirolimus reduced basic cell functions...
Background and Significance: Metabolic heart disease(MHD) is common in patients with obesity, type 2 diabetes and/or metabolic syndrome. We found cardiac mitochondrial dysfunction mice obesity-related MHD due to consumption of a high fat sucrose (HFHS) diet. The effects diet-induced obesity on energetics pump function the intact organ are largely unknown. Hypothesis: tested hypothesis that HFHS diet for one month impairs energetic contractile reserve heart. Methods Results: Mice were fed or...
The heart relies on mitochondria for its extensive energetic demands, and some cytoskeletal elements can regulate mitochondrial function. Cardiac troponin I (cTnI) is a structural protein involved in sarcomeric contraction. Here we demonstrate that cTnI localizes to mitochondria, inhibits functions, increases opening of the permeability transition pore under oxidative stress. Purified directly binds immune-captured ATP synthase saturable fashion doubles "reverse" F 1 0 -ATPase activity vitro...
Heart transplantation continues to be a life-saving therapy for patients with end-stage heart failure; yet the average long-term graft survival remains at only 12.5 years. Cardiac allograft vasculopathy (CAV) and cardiac dysfunction are both key contributors morbidity mortality in transplant population. Studies have suggested that immunosuppressive agents may modulate cardiovascular function, mechanisms this modulation is incompletely understood. The primary classes of utilized post-heart...
Abstract Despite therapeutic advancements, GVHD is a major complication of HSCT. In current models GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation microbes expressing Pathogen Associated Molecular Patterns (PAMPs), result in activation host antigen-presenting cells (APC) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that many pathologic states, results the release mitochondria from cytoplasm extracellular space. We...