A5011650333- Mitochondrial Function and Pathology
- Renal Diseases and Glomerulopathies
- Genetic and Kidney Cyst Diseases
- Pancreatic function and diabetes
- Biomedical Research and Pathophysiology
- Cardiac Ischemia and Reperfusion
- Hormonal Regulation and Hypertension
- Nitric Oxide and Endothelin Effects
- Autophagy in Disease and Therapy
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Neonatal Respiratory Health Research
- Metabolism and Genetic Disorders
- Nuclear Structure and Function
- RNA Research and Splicing
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Vagus Nerve Stimulation Research
- Neurogenesis and neuroplasticity mechanisms
- Renin-Angiotensin System Studies
- Bone Tissue Engineering Materials
- Spinal Dysraphism and Malformations
- Fetal and Pediatric Neurological Disorders
- Nicotinic Acetylcholine Receptors Study
- Surgical Sutures and Adhesives
- Adenosine and Purinergic Signaling
University of Iowa
2012-2025
Laboratoire de Chimie
2002
Abstract Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected patients and experimentally infected animals indicate a critical role for augmented expression proinflammatory chemokines cytokines in disease. Here, we demonstrate that SARS-CoV-2 infection human monocyte-derived macrophages (MDMs) dendritic cells was abortive, but induced the production multiple antiviral (interferon-α, interferon-β, tumor necrosis factor, interleukins 1β, 6, 10) chemokine (CXCL10)....
The ARF tumor suppressor is a nucleolar protein that activates p53-dependent checkpoints by binding Mdm2, p53 antagonist.Despite persuasive evidence can bind and inactivate Mdm2 in the nucleoplasm, prevailing view exerts its growth-inhibitory activities from within nucleolus.We suggest primarily functions outside nucleolus provide it sequestered held inactive compartment phosphoprotein, nucleophosmin (NPM).Most cellular bound to NPM regardless of whether cells are proliferating or growth...
Significance The photoreceptor outer segment (OS) is a cellular compartment that senses light in the eye. Structural and functional defects OS are common causes of inherited blindness. Bardet–Biedl syndrome (BBS) human genetic disease associated with defective protein trafficking However, it not well understood why or how photoreceptors die BBS. In this article, we show primary cause degeneration BBS likely aberrant accumulation non-OS proteins OS, which accompanied by disorganization...
Ca 2+ /calmodulin-dependent protein kinase (CaMKII) transduces oxidative stress into asthma-related diseases.
Type 1 diabetes (T1D) is caused by autoimmune disease that leads to the destruction of pancreatic β-cells. Transplantation cadaveric organs or islets can restore normal physiology. However, there a chronic shortage organs, limiting treatment majority patients on pancreas transplantation waiting list. Here, we hypothesized human iPS cells be directly differentiated into insulin producing (IPCs) capable secreting insulin. Using series growth factors, successfully generated derived IPCs....
High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due toxicities normal cells and there is a need target only tumor and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads formation highly reactive oxygen species (ROS) resulting cell death. PAA selectively kills CD138+ MM derived from smoldering (SMM) but not monoclonal gammopathy undetermined significance (MGUS)...
Significance Almost 20% of women and 40% men in the United States abuse alcohol or have experienced dependence their lifetime. Though accidents, traffic fatalities, violent crimes account for majority alcohol-involved mortalities, excessive, chronic drinking also causes often irreversible heart liver damage. We identify regulator G protein signaling 6 (RGS6) as a novel drug target with substantive potential clinical utility treatment alcoholism amelioration resultant hepatic cardiac...
Objective— The main objective of this study is to define the mechanisms by which mitochondria control vascular smooth muscle cell (VSMC) migration and impact neointimal hyperplasia. Approach Results— multifunctional CaMKII (Ca 2+ /calmodulin-dependent kinase II) in mitochondrial matrix VSMC drove a feed-forward circuit with Ca uniporter (MCU) promote influx. MCU was necessary for activation (mtCaMKII), whereas mtCaMKII phosphorylated at regulatory site S92 that promotes entry. sufficient...
During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of epithelial barrier required for reabsorption fluid. Tight junctions (TJ) maintain this barrier. We set out determine whether hypoxia creates dysfunctional barrier, evidenced by an increase in transepithelial electrical conductance (G t ), due decrease abundance TJ proteins at plasma membrane. Alveolar cells (AEC) mild (Po 2 = 50 mmHg) 30 and 60 min decreased occludin membrane significantly...
The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine important in transducing intracellular Ca2+ signals. While vitro data regarding the role of CaMKII regulation endothelial nitric oxide synthase (eNOS) are contradictory, its function vivo remains unknown. Using two novel transgenic models to express inhibitor peptides selectively endothelium, we examined effect on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline...
Mitochondria-ER contact sites (MERCS) are vital for mitochondrial dynamics, lipid exchange, Ca2+ homeostasis, and energy metabolism. We examined whether metabolism changes during the cell cycle depend on MERCS dynamics regulated by outer protein rho GTPase 1 (MIRO1). Wound healing was assessed in mice with fibroblast-specific deletion of MIRO1. Wild-type MIRO1-/- fibroblasts vascular smooth muscle cells were evaluated proliferation, progression, number MERCS, distance, composition throughout...
In multiple sclerosis (MS), demyelination is often accompanied by axonal lesions, which largely account for patient disability. We therefore studied the consequences of induced lysophosphatidylcholine (LPC) on cytoskeleton, particularly neurofilaments (NF) and tubulin, in adult rat corpus callosum. Immunocytochemistry showed that NF immunolabelled fibres decreased 49% LPC injured area at day 15. Since it has been previously demonstrated PDGF improves remyelination, we performed a comparative...
The calcium and calmodulin-dependent kinase II (CaMKII) translates increases in intracellular Ca(2+) into downstream signaling events. Its function pulmonary pathologies remains largely unknown. CaMKII is a well-known mediator of apoptosis regulator endoplasmic reticulum (ER) Ca(2+). ER stress type pneumocytes lead to aberrant tissue repair progressive collagen deposition fibrosis. Thus we hypothesized that inhibition alleviates fibrosis response bleomycin by attenuating pneumocytes. We...
Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency urge incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, an adult mouse model would expand opportunities to explore mechanisms in preclinical experiments. Here, we describe the first chronic, communicating pressure. Hydrocephalic male...
Abstract Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods efficiently breach barriers presented airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on previously reported S10 substantially improved base editor ribonucleoprotein (RNP) delivery. Studies secondary structure revealed alpha-helix formed endosomal leakage domain (ELD), not cell penetrating (CPP), was...
Background: The p.Arg218Gln (R218Q) mutation in the inverted formin 2 ( INF2 ) gene causes podocytopathy prone to focal segmental glomerulosclerosis (FSGS). This disrupts ability of sequester DYNLL1, thus promoting dynein-mediated mistrafficking slit diaphragm protein, nephrin, proteolytic pathways. Bortezomib, a proteasome inhibitor (PI), stabilizes nephrin R218Q knockin (KI) podocytes, suggesting role for ubiquitin system (UPS) dynein-driven pathogenesis. However, link between dynein and...
Abstract The human myelin/oligodendrocyte glycoprotein (MOG) gene is encoded by 10 exons that exhibit a complex pattern of alternative splicing. This report demonstrates several MOG‐specific splice variants are indeed expressed in oligodendrocytes (OLs) and myelin during perinatal development retained through adulthood. While all forms possess the common extracellular Ig‐like domain, these MOG structures differ significantly their respective cytoplasmic domains. Peptide‐specific antibodies...
Abstract TFEB promotes lysosomal biogenesis, autophagy, and exocytosis. The present study characterized the consequence of inducible overexpression in cardiomyocytes vivo. We generated cardiomyocyte-specific doxycycline (Tet off) mice to achieve spatial temporal control overexpression, by crossing transgenic with harboring tTA transgene (TFEB/tTA). Two weeks after removal, an 8-fold increase protein expression was observed hearts. Heart weight normalized tibia length increased 2.5-fold...
ABSTRACT Background The outer mitochondrial Rho GTPase 1, MIRO1, mediates motility within cells, but implications for vascular smooth muscle cell (VSMC) physiology and its roles invascular diseases, such as neointima formation following injury are widely unknown. Methods An in vivo model of selective Miro1 deletion VSMCs was generated, the animals were subjected to carotid artery ligation. molecular mechanisms relevant VSMC proliferation then explored explanted by imaging positioning cristae...