A5085824079- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Pluripotent Stem Cells Research
- Renal function and acid-base balance
- CRISPR and Genetic Engineering
- Hemodynamic Monitoring and Therapy
- 3D Printing in Biomedical Research
- Viral Infections and Immunology Research
- Biochemical and Molecular Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pulmonary Hypertension Research and Treatments
- Neonatal Respiratory Health Research
- Genetic and Kidney Cyst Diseases
- Muscle Physiology and Disorders
- Sepsis Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
- Heart Failure Treatment and Management
- Microtubule and mitosis dynamics
- Congenital Diaphragmatic Hernia Studies
- Coronary Artery Anomalies
- Signaling Pathways in Disease
- Sirtuins and Resveratrol in Medicine
Northwestern University
2014-2024
Lurie Children's Hospital
2013-2024
Evanston Hospital
2022
University of California, San Francisco
2003-2008
Boston Children's Hospital
2002
University of Colorado Denver
1999
University of Colorado Health
1999
University of Colorado Anschutz Medical Campus
1999
SIRT2 is a cytoplasmic sirtuin that plays role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized directly regulates iron homeostasis. Here, have demonstrated depletion results decrease levels both vitro vivo. Mechanistically, determined maintains by binding to deacetylating nuclear factor erythroid-derived 2-related 2 (NRF2) on lysines 506 508, leading reduction total NRF2 levels. The leads reduced...
Human induced pluripotent stem cell (hiPSC) culture has become routine, yet the cost of media, frequent medium changes, and reproducibility differentiation have remained restrictive. Here, we describe formulation a hiPSC (B8) as result exhaustive optimization constituents concentrations, establishing necessity relative contributions each component to state proliferation. The reagents in B8 represent only 3% costs commercial made possible primarily by in-lab generation three E....
Many eukaryotic proteins are posttranslationally modified by the esterification of cysteine thiols to long-chain fatty acids. This modification, protein palmitoylation, is catalyzed a large family palmitoyl acyltransferases that share an Asp-His-His-Cys Cys-rich domain but differ in their subcellular localizations and substrate specificities. In Trypanosoma brucei, flagellated protozoan parasite causes African sleeping sickness, palmitoylation has been observed for few proteins, extent...
Protein palmitoylation has diverse effects in regulating protein membrane affinity, localization, binding partner interactions, turnover and function. Here, we show that also contributes to the sorting of proteins eukaryotic flagellum. African trypanosomes are protozoan pathogens express a family unique Ca2+-binding proteins, calflagins, which undergo N-terminal myristoylation palmitoylation. The localization calflagins depends on their acylation status. Myristoylation alone is sufficient...
ABSTRACT African trypanosomes express a family of dually acylated, EF-hand calcium-binding proteins called the calflagins. These associate with lipid raft microdomains in flagellar membrane, where they putatively function as calcium signaling proteins. Here we show that these bind high affinity and their expression is regulated during life cycle stage parasite, protein levels approximately 10-fold higher mammalian bloodstream form than insect vector procyclic stage. We also demonstrate role...
The flagellar calcium-binding protein (FCaBP) of Trypanosoma cruzi is localized to the membrane in all life cycle stages parasite. Myristoylation and palmitoylation N terminus FCaBP are necessary for targeting. Not dually acylated proteins T. flagellar, however. Other determinants therefore likely contribute specificity. We generated transfectants expressing N-terminal 24 or 12 amino acids fused GFP. Analysis these mutants revealed that although 1-12 sufficient dual acylation binding, 13-24...
Extracellular signaling pathways regulating myoblast differentiation and cell-cycle withdrawal are not completely understood. Stem cell antigen-1 (Sca-1/Ly-6A/E) is a glycosylphosphatidylinositol-anchored membrane protein known for its role in T-cell activation, recently described as marker regeneration-competent myoblasts. We previously determined that expression of Sca-1/Ly-6A transiently upregulated during myocyte withdrawal; however, specific function Sca-1 myogenesis has been described....
Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially fatal cardiomyopathy often associated with cardiac autoimmunity. T. cruzi infection induces development of autoimmunity to number antigens via molecular mimicry and other mechanisms, but genesis pathogenic potential this autoimmune response has not been fully elucidated. To determine whether exposure alone in absence active sufficient induce autoimmunity, we immunized A/J mice heat-killed (HKTC)...
Abstract Stem cell antigen‐1 (Sca‐1, Ly6A/E) is a glycosylphosphotidylinositol‐anchored protein that identifies many tissue progenitor cells. We originally identified Sca‐1 as marker of myogenic precursor cells and subsequently demonstrated regulates proliferation activated myoblasts, suggesting an important role for in skeletal muscle homeostasis. Beyond its functional regulating proliferation, however, little known about the mechanism(s) drive Sca‐1‐mediated events. now report lipid...
Infection with the protozoan parasite Trypanosoma cruzi may lead to a potentially fatal cardiomyopathy known as Chagas heart disease. This disease is characterized by infiltration of myocardium mononuclear cells, including CD4+ T together edema, myofibrillary destruction, and fibrosis. A multifaceted systemic immune response develops that ultimately keeps parasitemia tissue parasitosis low. helper 1 other pro-inflammatory cell responses are effective at keeping levels T. low in tissues...
Chagas heart disease, the leading cause of failure in Latin America, results from infection with parasite Trypanosoma cruzi. Although T. cruzi disseminates intravascularly, how contends endothelial barrier to escape bloodstream and infect tissues has not been described. Understanding interaction between vascular endothelium, likely a key step dissemination, could inform future therapies interrupt disease pathogenesis. We adapted systems useful study leukocyte transmigration investigate both...
Sphingolipids are important constituents of cell membranes and also serve as mediators signaling recognition. Sphingolipid metabolites such sphingosine-1-phosphate ceramide regulate cascades involved in proliferation differentiation, autophagy, inflammation, apoptosis. Little is known about how sphingolipids their function single-celled eukaryotes. In the present study, we investigated role sphingosine kinase (SPHK) biology protozoan parasite Trypanosoma brucei, agent African sleeping...
Abstract Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations sterol-rich rafts. The African trypanosome Trypanosoma brucei is single-celled eukaryote with single cilium/flagellum. We tested whether flagellar sterol enrichment results from selective partitioning specific species or general all sterols. While sterols are enriched flagellum, cholesterol especially enriched. T. cycles between its mammalian...
Objectives: Soluble MER has emerged as a potential biomarker for delayed resolution of inflammation after myocardial injury and therapeutic target to reduce cardiac-related morbidity mortality in adults. The significance soluble pediatric populations, however, is unclear. We sought investigate if concentrations change response ischemia reperfusion patients. In parallel, we also correlations between the concentration specific patient, bypass, postoperative data. Design: quantified plasma...
Objective The objective of this study was to characterize the natural history metabolic uncoupling (type B hyperlactemia and hyperglycemia) following cardiopulmonary bypass (CPB), determine impact insulin therapy on time lactate normalization in patients without low cardiac output. Design design used a retrospective cohort study. Setting set pediatric intensive care unit tertiary-care urban children's hospital. Patients All were aged ≤21 years admitted between 2007 2013 surgery involving CPB...