Omid Haji-Ghassemi

Omid Haji-Ghassemi
The University of Calgary | HBI · Department of Biological Sciences

Doctor of Philosophy (Biochemistry)

About

39
Publications
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333
Citations
Introduction
I am interested in ion channel regulation in neuronal and muscle cell systems. My research program spans from adapter proteins to enzymes that regulate ion channels. To achieve this the lab focuses on protein-protein interactions using structural biology methods such as X-ray crystallography and single particle cryo-EM in conjunction with ancillary methods such as biochemical and biophysical assays.

Publications

Publications (39)
Article
Diamide insecticides target insect ryanodine receptors (RYRs) and cause dysregulation of calcium signaling in insect muscles and neurons, generating worldwide sales over 2 billion US dollars annually. Several resistance mutations have been reported to reduce the efficacy of the diamides, but the exact binding sites and mechanism of resistance mutat...
Article
Full-text available
Cardiac troponin C (cTnC) is the critical Ca2+ sensing component of the troponin complex. Binding of Ca2+ to cTnC triggers a cascade of conformational changes within the myofilament that culminate in force production. Hypertrophic cardiomyopathy (HCM) associated TNNC1 variants generally induce a greater degree and duration of Ca2+ binding, which ma...
Article
Full-text available
Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca ²⁺ -ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent p...
Preprint
Full-text available
Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca ²⁺ -ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent p...
Article
BACKGROUND Stress signaling typically involves stimulation of the β-adrenergic pathway which leads to the subsequent activation of cAMP-dependent protein kinase A (PKA). PKA has thus been proposed to regulate calcium entry into cardiomyocytes during stress signaling via the L-type calcium channel (CaV1.2) and the ryanodine receptor 2 (RyR2). Ryanod...
Preprint
Full-text available
Cardiac troponin C (cTnC) is the calcium (Ca ²⁺ ) sensing component of the troponin complex. Binding of Ca ²⁺ to cTnC triggers a cascade of myofilament conformational changes that culminate in force production. Mutations in cTnC linked to hypertrophic myocardial myopathy (HCM) induce a a greater degree and duration of Ca ²⁺ binding, which may under...
Article
Full-text available
Ryanodine Receptors (RyRs) are massive channels that release Ca2+ from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects...
Article
Full-text available
The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL)....
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of cortical, brain stem and spinal motor neurons that leads to muscle weakness and death. A previous study implicated CACNA1H encoding for Cav3.2 calcium channels as a susceptibility gene in ALS. In the present study, two heterozygous CACNA1H v...
Article
Ryanodine receptors (RyRs) are intracellular Ca2+ release channels controlling essential cellular functions. RyRs are targeted by cyclic AMP (cAMP)-dependent protein kinase A (PKA), a controversial regulation implicated in disorders ranging from heart failure to Alzheimer’s. Using crystal structures, we show that the phosphorylation hotspot domain...
Article
Ryanodine Receptors (RyRs) are large intracellular channels that control the release of Ca2þ from the SR or ER. They are targets for a multitude of regulatory events, including the phosphorylation by kinases like PKA and CaMKII. Here we provide direct crystallographic insights into the recognition of RyR2, the cardiac isoform, by PKA. We found an e...
Article
Murine antibodies S25-23, S25-26 and S25-5 derive from a common germ-line origin and all bind the Chlamydiaceae family-specific epitope αKdo(2→8)αKdo(2→4)αKdo, (where Kdo is 3-deoxy-α-D-manno-oct-2-ulosonic acid) with high affinity and specificity. These antibodies recognize the entire trisaccharide antigen in a linkage dependent manner via a groov...
Article
Full-text available
Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants. Methods The phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysi...
Data
Pedigrees of select multi-variant families. (DOCX)
Data
Detailed classification scheme for all variants in the population. (DOCX)
Data
Detailed material and methodology. (DOCX)
Article
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants. Methods The phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysiology Socie...
Article
Full-text available
Self-assembling protein surface (S-) layers are common cell envelope structures of prokaryotes and have critical roles from structural maintenance to virulence. S-layers of Gram-positive bacteria are often attached through the interaction of S-layer homology (SLH) domain trimers with peptidoglycan-linked secondary cell wall polymers (SCWPs). Here w...
Article
Full-text available
Homologous glycosyltransferases GTA and GTB perform the final step in human ABO(H) blood group A and B antigen synthesis by transferring the sugar moiety from donor UDP-GalNAc/UDP-Gal to the terminal H antigen disaccharide acceptor. Like other GT-A fold family 6 glycosyltransferases, GTA and GTB undergo major conformational changes in two mobile re...
Article
The process of natural selection favours germ-line gene segments that encode CDRs that have the ability to recognize a range of structurally related antigens. This presents an immunological advantage to the host, as it can confer protection against a common pathogen and still cope with new or changing antigens. Cross-reactive and polyspecific antib...
Article
Full-text available
Aberrant glycosylation and the overexpression of specific carbohydrate epitopes is a hallmark of many cancers, and tumor-associated oligo-saccharides are actively investigated as targets for immunotherapy and diagnostics. Wisteria floribunda agglutinin (WFA) is a legume lectin that recognizes terminal N-acetylgalactosaminides with high affinity. WF...
Article
Full-text available
Lipopolysaccharide dispersed in the blood by Gram-negative bacteria can be a potent inducer of septic shock. One research focus has been based on antibody sequestration of lipid A (the endotoxic principle of LPS), however none have been successfully developed into a clinical treatment. Comparison of a panel of anti-lipid A antibodies reveals highly...
Article
Full-text available
Homologous glycosyltransferases GTA and GTB catalyze the final step in ABO(H) blood group A and B antigen synthesis through sugar transfer from activated donor to the H antigen acceptor. These enzymes have a GT-A-fold-type with characteristic mobile polypeptide loops that cover the active site upon substrate binding and, despite intense investigati...
Article
Full-text available
Septic shock is a leading cause of death, and, results from an inflammatory cascade triggered by the presence of microbial products in the blood. Certain LPS from Gram-negative bacteria are very potent inducers and responsible for a high percentage of septic shock cases. Despite decades of research, mAbs specific for lipid A (the endotoxic principl...
Article
Full-text available
Carbohydrate antigens are valuable as components of vaccines for bacterial infectious agents and human immunodeficiency virus (HIV), and for generating immunotherapeutics against cancer. The crystal structures of anti-carbohydrate antibodies in complex with antigen reveal the key features of antigen recognition and provide information that can guid...
Article
Full-text available
The structure of the antigen-binding fragment of mAb S25-26 determined to 1.95 Å resolution in complex with the Chlamydiaceae family-specific trisaccharide antigen Kdo(2→8)-Kdo(2→4)Kdo (Kdo=3-deoxy-α-D-manno-oct-2-ulopyranosonic acid) displays a germline-coded paratope that differs significantly from previously characterized Chlamydiaceae-specific...
Conference Paper
Full-text available
Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine k...

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