Conrad L Epting

Northwestern University | NU · Department of Pediatrics

The reprogramming of somatic cells to a spontaneously contracting cardiomyocyte-like state using defined transcription factors has proven successful in mouse fibroblasts. However, this process has been less successful in human cells, thus limiting the potential clinical applicability of this technology in regenerative medicine. We hypothesized that...

The reprogramming of somatic cells to a spontaneously contracting cardiomyocyte-like state using defined transcription factors has proven successful in mouse fibroblasts. However, this process has been less successful in human cells, thus limiting the potential clinical applicability of this technology in regenerative medicine. We hypothesized that...

Dynamic post-translational modifications allow the rapid, specific, and tunable regulation of protein functions in eukaryotic cells. S-acylation is the only reversible lipid modification of proteins, in which a fatty acid, usually palmitate, is covalently attached to a cysteine residue of a protein by a zDHHC palmitoyl acyltransferase enzyme. Depal...

The reprogramming of somatic cells to a spontaneously contracting cardiomyocyte-like state using defined transcription factors has proven successful in mouse fibroblasts, but has been less successful with human cells, limiting the potential clinical applicability of this technology in regenerative medicine. We hypothesized that this issue is due to...

Objectives: Soluble MER has emerged as a potential biomarker for delayed resolution of inflammation after myocardial injury and a therapeutic target to reduce cardiac-related morbidity and mortality in adults. The significance of soluble MER in pediatric populations, however, is unclear. We sought to investigate if soluble MER concentrations chang...

While hyperlactatemia in postoperative cardiac surgery patients was once believed to solely reflect hypoperfusion, either from the accumulated “oxygen debt” during bypass or ongoing inadequate perfusion, our understanding of lactate generation, clearance, and management has evolved. A contemporary understanding of lactate balance is critical to the...

Human induced pluripotent stem cell (hiPSC) culture has become routine, yet the cost of pluripotent cell media, frequent medium changes, and the reproducibility of differentiation have remained restrictive. Here, we describe the formulation of a hiPSC culture medium (B8) as a result of the exhaustive optimization of medium constituents and concentr...

Human induced pluripotent stem cell (hiPSC) culture has become routine, yet pluripotent cell media costs, frequent media changes, and reproducibility of differentiation have remained restrictive, limiting the potential for large-scale projects. Here, we describe the formulation of a novel hiPSC culture medium (B8) as a result of the exhaustive opti...

Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations of sterol-rich lipid rafts. The African trypanosome Trypanosoma brucei is a single-celled eukaryote with a single cilium/flagellum. We tested whether flagellar sterol enrichment results from selective flagel...

African trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma brucei . During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes, T. brucei has a cell cycle involving the de novo synthesis of DNA regulated by ribonucl...

SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron levels both in vitr...

Objectives: Focusing on critically ill children with cardiac disease, we will review common causes of fluid perturbations, clinical recognition, and strategies to minimize and treat fluid-related complications. Data source: MEDLINE and PubMed. Conclusions: Meticulous fluid management is vital in critically ill children with cardiac disease. Fl...

Low cardiac output syndrome frequently complicates the post-operative care of infants and children following cardiac surgery. The onset of low cardiac output follows a predictable course in the hours following cardiopulmonary bypass, as myocardial performance declines in the face of an elevated demand for cardiac output. When demand outstrips suppl...

Unlabelled: Sphingolipids are important constituents of cell membranes and also serve as mediators of cell signaling and cell recognition. Sphingolipid metabolites such as sphingosine-1-phosphate and ceramide regulate signaling cascades involved in cell proliferation and differentiation, autophagy, inflammation, and apoptosis. Little is known abou...

This review offers a critical-care perspective on the pathophysiology, monitoring, and management of acute heart failure syndromes in children. An in-depth understanding of the cardiovascular physiological disturbances in this population of patients is essential to correctly interpret clinical signs, symptoms and monitoring data, and to implement a...

The objective of this study was to characterize the natural history of metabolic uncoupling (type B hyperlactemia and hyperglycemia) following cardiopulmonary bypass (CPB), and to determine the impact of insulin therapy on time to lactate normalization in patients without low cardiac output. The design used was a retrospective cohort study. The stu...

We report the case of a child with both propionic acidemia and cyanotic congenital heart disease. The presence of an underlying inborn error of metabolism confounded the management of this patient in the postoperative period, resulting in therapeutic misdirection until the true etiology of hyperlactemia was recognized. © The Author(s) 2014.

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 the myocardium by mononuclear cells, including CD4+ T cells, together with edema, myofibrillary destruction, and fibrosis. A multifaceted systemic immune response deve...

Sepsis is a clinical syndrome characterized by activation of the host inflammatory system in response to infection. The initial phase, manifested by shock, fever, and hypermetabolism, is largely secondary to a hyperinflammatory state and is responsible for the classic signs and symptoms of early sepsis. This review focuses on the early events after...

Chagas heart disease, the leading cause of heart failure in Latin America, results from infection with the parasite Trypanosoma cruzi. Although T. cruzi disseminates intravascularly, how the parasite contends with the endothelial barrier to escape the bloodstream and infect tissues has not been described. Understanding the interaction between T. cr...

Introduction: Chagas heart disease, caused by infection with Trypanosoma cruzi, is the leading cause of heart failure in Latin America. Although the clinical manifestations of Chagas disease are tissue-restricted, a relationship between tissue targeting and cardiac disease has never been established. Our research investigates the basis for this car...

Hexokinase-II (HKII) is highly expressed in the heart and can bind to the mitochondrial outer membrane. Since cardiac hypertrophy is associated with a substrate switch from fatty acid to glucose, we hypothesized that a reduction in HKII would decrease cardiac hypertrophy after pressure overload. Contrary to our hypothesis, heterozygous HKII-deficie...

The flagellar calcium-binding protein (FCaBP) of Trypanosoma cruzi is localized to the flagellar membrane in all life cycle stages of the parasite. Myristoylation and palmitoylation of the N terminus of FCaBP are necessary for flagellar membrane targeting. Not all dually acylated proteins in T. cruzi are flagellar, however. Other determinants of FC...

[This corrects the article on p. e14571 in vol. 6.].

Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially fatal cardiomyopathy often associated with cardiac autoimmunity. T. cruzi infection induces the development of autoimmunity to a number of antigens via molecular mimicry and other mechanisms, but the genesis and pathogenic potential of this autoimmune respons...

Many eukaryotic proteins are posttranslationally modified by the esterification of cysteine thiols to long-chain fatty acids. This modification, protein palmitoylation, is catalyzed by a large family of palmitoyl acyltransferases that share an Asp-His-His-Cys Cys-rich domain but differ in their subcellular localizations and substrate specificities....

The protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, is an obligate intracellular protozoan pathogen. Overlapping mechanisms ensure successful infection, yet the relationship between these cellular events and clinical disease remains obscure. This review explores the process of cell invasion from the perspective of cell...

A cilium is an extension of the cell that contains an axonemal complex of microtubules and associated proteins bounded by a membrane which is contiguous with the cell body membrane. Cilia may be nonmotile or motile, the latter having additional specific roles in cell or fluid movement. The term flagellum refers to the motile cilium of free-living s...

Chagas heart disease (CHD), caused by the parasite Trypanosoma cruzi, is a potentially fatal myocarditis associated with cardiac autoimmunity. Immunization of A/J mice with heat-killed T. cruzi (HKTC) induces acute cardiac damage and polyantigenic humoral and cellular autoimmunity of a specificity and magnitude similar to that observed in infected...

African trypanosomes express a family of dually acylated, EF-hand calcium-binding proteins called the calflagins. These proteins associate with lipid raft microdomains in the flagellar membrane, where they putatively function as calcium signaling proteins. Here we show that these proteins bind calcium with high affinity and that their expression is...

Protein palmitoylation has diverse effects in regulating protein membrane affinity, localization, binding partner interactions, turnover and function. Here, we show that palmitoylation also contributes to the sorting of proteins to the eukaryotic flagellum. African trypanosomes are protozoan pathogens that express a family of unique Ca(2+)-binding...

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 a marker of myogenic precursor cells and subsequently demonstrated that Sca-1 regulates proliferation of activated myoblasts, suggesting an important role for Sca-1 in skeletal muscle...

Skeletal muscle repair occurs through a programmed series of events including myogenic precursor activation, myoblast proliferation, and differentiation into new myofibers. We previously identified a role for Stem cell antigen-1 (Sca-1) in myoblast proliferation and differentiation in vitro. We demonstrated that blocking Sca-1 expression resulted i...

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, and recently described as a marker for regeneration-competent myoblasts. We previously...

Genetic studies have shown that CDC5 proteins are essential for G2 progression and mitotic entry. CDC5 homologs in yeast and mammals are essential for pre-messenger ribonucleic acid (mRNA) processing. Other gene products also have been shown to play roles in both pre-mRNA splicing and cell cycle regulation, prompting the description of several mode...

We describe a 2-year-old child with severe pulmonary hypertension due to a patent ductus arteriosus (PDA) with plexiform lesions on lung biopsy. Despite high basal pulmonary vascular resistance with minimal responsiveness to inhaled nitric oxide and other vasodilators, and advanced plexogenic arteriopathy on lung biopsy, her pulmonary hypertension...

We describe a timetable of events during programmed cell death (PCD) in neuronal PC12 cells, specifically, Ras signaling, immediate-early gene (IEG) expression, DNA fragmentation and commitment to PCD. Commitment occurs over a period from 10-20 hr after NGF withdrawal. Ras signaling declines rapidly after NGF removal, reaching minimal levels within...