Scholars@Duke
Erik James Soderblom

Erik James Soderblom

Associate Research Professor of Cell Biology
Cell Biology
erik.soderblom@duke.edu
701 W Main St., Suite 310, Durham, NC 27708
701 W Main St., Suite 320, Durham, NC 27708

Selected Publications

Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions.

Journal Article Nat Commun · August 9, 2024 One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism ri ... Full text Link to item Cite

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

Journal Article Elife · July 24, 2024 One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associat ... Full text Link to item Cite

Deciphering the TET3 interactome in primary thymic developing T cells.

Journal Article iScience · May 17, 2024 Ten-eleven translocation (TET) proteins are DNA dioxygenases that mediate active DNA demethylation. TET3 is the most highly expressed TET protein in thymic developing T cells. TET3, either independently or in cooperation with TET1 or TET2, has been implica ... Full text Link to item Cite

Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Journal Article Sci Transl Med · May 2024 Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be update ... Full text Link to item Cite

An osteoarthritis pathophysiological continuum revealed by molecular biomarkers.

Journal Article Sci Adv · April 26, 2024 We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six serum peptides, corresponding to six proteins, reached AUC 77% probability to distinguis ... Full text Link to item Cite

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-RKT.

Journal Article Cell Rep · March 26, 2024 An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274 ... Full text Link to item Cite

Serum proteomic biomarkers diagnostic of knee osteoarthritis.

Conference Osteoarthritis Cartilage · March 2024 OBJECTIVE: To better understand the pathogenesis of knee osteoarthritis (OA) through identification of serum diagnostics. DESIGN: We conducted multiple reaction monitoring mass spectrometry analysis of 107 peptides in baseline sera of two cohorts: the Foun ... Full text Link to item Cite

Serum proteomic panel validated for prediction of knee osteoarthritis progression.

Journal Article Osteoarthr Cartil Open · March 2024 OBJECTIVE: To further validate a serum proteomics panel for predicting radiographic (structural) knee OA progression. DESIGN: Serum peptides were targeted by multiple-reaction-monitoring mass spectrometry in the New York University cohort (n ​= ​104). Knee ... Full text Link to item Cite

Assessing Trans-Inhibition of OATP1B1 and OATP1B3 by Calcineurin and/or PPIase Inhibitors and Global Identification of OATP1B1/3-Associated Proteins

Journal Article Pharmaceutics · January 1, 2024 Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are key determinants of drug–drug interactions (DDIs). Various drugs including the calcineurin inhibitor (CNI) cyclosporine A (CsA) exert preincubation-induced trans-inhibitory effects upon OATP ... Full text Cite

Immune system-related plasma extracellular vesicles in healthy aging.

Journal Article Front Immunol · 2024 OBJECTIVES: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. METHODS: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial fre ... Full text Link to item Cite

Comprehensive characterization of pathogenic synovial fluid extracellular vesicles from knee osteoarthritis.

Journal Article Clin Immunol · December 2023 Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were pos ... Full text Link to item Cite

Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice.

Journal Article Cell Rep · October 31, 2023 The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vacc ... Full text Link to item Cite

Signal transduction at GPCRs: Allosteric activation of the ERK MAPK by β-arrestin.

Journal Article Proc Natl Acad Sci U S A · October 24, 2023 β-arrestins are multivalent adaptor proteins that bind active phosphorylated G protein-coupled receptors (GPCRs) to inhibit G protein signaling, mediate receptor internalization, and initiate alternative signaling events. β-arrestins link agonist-stimulate ... Full text Link to item Cite

O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations.

Journal Article Nat Commun · October 17, 2023 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly ... Full text Link to item Cite

Crosstalk between RNA m6A and DNA methylation regulates transposable element chromatin activation and cell fate in human pluripotent stem cells.

Journal Article Nat Genet · August 2023 Transposable elements (TEs) are parasitic DNA sequences accounting for over half of the human genome. Tight control of the repression and activation states of TEs is critical for genome integrity, development, immunity and diseases, including cancer. Howev ... Full text Link to item Cite

Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling.

Journal Article J Cell Physiol · March 2023 A common adverse response to the clinical use of glucocorticoids (GCs) is elevated intraocular pressure (IOP) which is a major risk factor for glaucoma. Elevated IOP arises due to impaired outflow of aqueous humor (AH) through the trabecular meshwork (TM). ... Full text Link to item Cite

A "best-in-class" systemic biomarker predictor of clinically relevant knee osteoarthritis structural and pain progression.

Journal Article Sci Adv · January 25, 2023 We aimed to identify markers in blood (serum) to predict clinically relevant knee osteoarthritis (OA) progression defined as the combination of both joint structure and pain worsening over 48 months. A set of 15 serum proteomic markers corresponding to 13 ... Full text Link to item Cite

GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans.

Journal Article Sci Adv · December 21, 2022 Aging causes functional decline and degeneration of neurons and is a major risk factor of neurodegenerative diseases. To investigate the molecular mechanisms underlying neuronal aging, we developed a new pipeline for neuronal proteomic profiling in young a ... Full text Link to item Cite

Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus.

Journal Article J Fungi (Basel) · March 30, 2022 Cellular recycling via autophagy-associated proteins is a key catabolic pathway critical to invasive fungal pathogen growth and virulence in the nutrient-limited host environment. Protein kinase A (PKA) is vital for the growth and virulence of numerous fun ... Full text Link to item Cite

Dataset on the mass spectrometry-based proteomic profiling of mouse embryonic fibroblasts from a wild type and DYT-TOR1A mouse model of dystonia, basally and during stress.

Journal Article Data Brief · December 2021 Here, we present quantitative subcellular compartment-specific proteomic data from wildtype and DYT-TOR1A heterozygous mouse embryonic fibroblasts (MEFs) basally and following thapsigargin (Tg) treatment [1]. In this experiment, we generated MEFs from wild ... Full text Link to item Cite

Cnksr2 Loss in Mice Leads to Increased Neural Activity and Behavioral Phenotypes of Epilepsy-Aphasia Syndrome.

Journal Article J Neurosci · November 17, 2021 Epilepsy Aphasia Syndromes (EAS) are a spectrum of childhood epileptic, cognitive, and language disorders of unknown etiology. CNKSR2 is a strong X-linked candidate gene implicated in EAS; however, there have been no studies of genetic models to dissect ho ... Full text Link to item Cite

BioID reveals an ATG9A interaction with ATG13-ATG101 in the degradation of p62/SQSTM1-ubiquitin clusters.

Journal Article EMBO Rep · October 5, 2021 ATG9A, the only multi-pass transmembrane protein among core ATG proteins, is an essential regulator of autophagy, yet its regulatory mechanisms and network of interactions are poorly understood. Through quantitative BioID proteomics, we identify a network ... Full text Link to item Cite

TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.

Journal Article Nat Commun · September 9, 2021 TNK1 is a non-receptor tyrosine kinase with poorly understood biological function and regulation. Here, we identify TNK1 dependencies in primary human cancers. We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction be ... Full text Link to item Cite

Action potential-coupled Rho GTPase signaling drives presynaptic plasticity.

Journal Article Elife · July 16, 2021 In contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling to presynaptic plasticity remain controversial and poorly understood. To identify and evaluate these signaling pathways, we conducted a proteomic ... Full text Link to item Cite

Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans.

Journal Article Elife · March 22, 2021 Mutation of the Wiskott-Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revea ... Full text Open Access Link to item Cite

The Protein Kinase A-Dependent Phosphoproteome of the Human Pathogen Aspergillus fumigatus Reveals Diverse Virulence-Associated Kinase Targets.

Journal Article mBio · December 15, 2020 Protein kinase A (PKA) signaling plays a critical role in the growth and development of all eukaryotic microbes. However, few direct targets have been characterized in any organism. The fungus Aspergillus fumigatus is a leading infectious cause of death in ... Full text Open Access Link to item Cite

Chemico-genetic discovery of astrocytic control of inhibition in vivo.

Journal Article Nature · December 2020 Perisynaptic astrocytic processes are an integral part of central nervous system synapses1,2; however, the molecular mechanisms that govern astrocyte-synapse adhesions and how astrocyte contacts control synapse formation and function are largely unknown. H ... Full text Link to item Cite

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Journal Article Front Oncol · 2020 Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, su ... Full text Link to item Cite

CDK12 Activity-Dependent Phosphorylation Events in Human Cells.

Journal Article Biomolecules · October 22, 2019 We asked whether the C-terminal repeat domain (CTD) kinase, CDK12/CyclinK, phosphorylates substrates in addition to the CTD of RPB1, using our CDK12analog-sensitive HeLa cell line to investigate CDK12 activity-dependent phosphorylation events in human cell ... Full text Link to item Cite

Calcineurin-dependent dephosphorylation of the transcription factor CrzA at specific sites controls conidiation, stress tolerance, and virulence of Aspergillus fumigatus.

Journal Article Mol Microbiol · July 2019 Calcium signaling through calcineurin and its major transcription factor (TF), CrzA, is integral to hyphal growth, stress response and virulence of the pathogenic fungus Aspergillus fumigatus, the leading etiology of invasive aspergillosis. Dephosphorylati ... Full text Link to item Cite

Immediate Release of Gastrin-Releasing Peptide Mediates Delayed Radiation-Induced Pulmonary Fibrosis.

Journal Article Am J Pathol · May 2019 Radiation-induced pulmonary fibrosis (RTPF) is a progressive, serious condition in many subjects treated for thoracic malignancies or after accidental nuclear exposure. No biomarker exists for identifying the irradiated subjects most susceptible to pulmona ... Full text Link to item Cite

In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation.

Journal Article Nat Commun · January 23, 2019 Excitatory synapse formation during development involves the complex orchestration of both structural and functional alterations at the postsynapse. However, the molecular mechanisms that underlie excitatory synaptogenesis are only partially resolved, in p ... Full text Link to item Cite

Hypothesis testing with proteomics: A case study using wound healing mechanisms in fluids associated with barnacle glue

Journal Article Frontiers in Marine Science · January 1, 2019 Growth, molting, and hardening cuticle are intertwined processes for arthropods and share common protein systems to execute these functions. For barnacles, these processes are also tied to adhesion, which is vital to their survival and under great selectio ... Full text Cite

Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.

Journal Article Nat Commun · December 5, 2018 The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that young macrophage cells produce factors that promote ost ... Full text Open Access Link to item Cite

Kin1 kinase localizes at the hyphal septum and is dephosphorylated by calcineurin but is dispensable for septation and virulence in the human pathogen Aspergillus fumigatus.

Journal Article Biochem Biophys Res Commun · November 2, 2018 Studies in yeasts have implicated the importance of Kin1 protein kinase, a member of the eukaryotic PAR1/MARK/MELK family, in polarized growth, cell division and septation through coordinated activity with the phosphatase, calcineurin. Kin1 is also require ... Full text Link to item Cite

Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · November 1, 2018 In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with ... Full text Link to item Cite

Proteomics and immunohistochemistry identify the expression of α-cardiac myosin heavy chain in the jaw-closing muscles of sooty mangabeys (order Primates).

Journal Article Arch Oral Biol · July 2018 OBJECTIVE: The jaw-closing muscles of humans and nonprimate mammals express alpha-cardiac fibers but MyHC α-cardiac has not been identified in the jaw adductors of nonhuman primates. We determined whether MyHC α-cardiac is expressed in the superficial mass ... Full text Link to item Cite

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

Journal Article Proc Natl Acad Sci U S A · June 5, 2018 O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events rema ... Full text Open Access Link to item Cite

The proximity-labeling technique BioID identifies sorting nexin 6 as a member of the insulin-like growth factor 1 (IGF1)-IGF1 receptor pathway.

Journal Article J Biol Chem · April 27, 2018 The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase with critical roles in various biological processes. Recent results from clinical trials targeting IGF1R indicate that IGF1R signaling pathways are more complex than previously ... Full text Link to item Cite

The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif.

Journal Article Vet Immunol Immunopathol · March 2018 Ideally, CD8+ T-cell responses against virally infected or malignant cells are defined at the level of the specific peptide and restricting MHC class I element, a determination not yet made in the dog. To advance the discovery of canine CTL epitopes, we so ... Full text Link to item Cite

The tail domain of the Aspergillus fumigatus class V myosin MyoE orchestrates septal localization and hyphal growth.

Journal Article J Cell Sci · February 7, 2018 Myosins are critical motor proteins that contribute to the secretory pathway, polarized growth, and cytokinesis. The globular tail domains of class V myosins have been shown to be important for cargo binding and actin cable organization. Additionally, phos ... Full text Link to item Cite

Scanning Quadrupole Data-Independent Acquisition, Part A: Qualitative and Quantitative Characterization.

Journal Article J Proteome Res · February 2, 2018 A novel data-independent acquisition (DIA) method incorporating a scanning quadrupole in front of a collision cell and orthogonal acceleration time-of-flight mass analyzer is described. The method has been characterized for the qualitative and quantitative ... Full text Link to item Cite

Scanning Quadrupole Data-Independent Acquisition, Part B: Application to the Analysis of the Calcineurin-Interacting Proteins during Treatment of Aspergillus fumigatus with Azole and Echinocandin Antifungal Drugs.

Journal Article J Proteome Res · February 2, 2018 Calcineurin is a critical cell-signaling protein that orchestrates growth, stress response, virulence, and antifungal drug resistance in several fungal pathogens. Blocking calcineurin signaling increases the efficacy of several currently available antifung ... Full text Link to item Cite

Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.

Journal Article Biochemistry · January 9, 2018 The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing ... Full text Open Access Link to item Cite

A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.

Journal Article Front Endocrinol (Lausanne) · 2018 O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurod ... Full text Open Access Link to item Cite

Phosphorylation of Aspergillus fumigatus PkaR impacts growth and cell wall integrity through novel mechanisms.

Journal Article FEBS Lett · November 2017 Protein kinase A (PKA) signaling is essential for growth and virulence of the fungal pathogen Aspergillus fumigatus. Little is known concerning the regulation of this pathway in filamentous fungi. Employing liquid chromatography-tandem mass spectroscopy, w ... Full text Link to item Cite

Acylation of Superoxide Dismutase 1 (SOD1) at K122 Governs SOD1-Mediated Inhibition of Mitochondrial Respiration.

Journal Article Mol Cell Biol · October 15, 2017 In this study, we employed proteomics to identify mechanisms of posttranslational regulation on cell survival signaling proteins. We focused on Cu-Zn superoxide dismutase (SOD1), which protects cells from oxidative stress. We found that acylation of K122 o ... Full text Link to item Cite

A Genoproteomic Approach to Detect Peptide Markers of Bacterial Respiratory Pathogens.

Journal Article Clin Chem · August 2017 BACKGROUND: Rapid identification of respiratory pathogens may facilitate targeted antimicrobial therapy. Direct identification of bacteria in bronchoalveolar lavage (BAL) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is co ... Full text Link to item Cite

Glycosylation of KEAP1 links nutrient sensing to redox stress signaling.

Journal Article EMBO J · August 1, 2017 O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations i ... Full text Open Access Link to item Cite

Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.

Journal Article Biochem Biophys Res Commun · April 1, 2017 Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators ... Full text Link to item Cite

Probing the Allosteric Role of the α5 Subunit of α3β4α5 Nicotinic Acetylcholine Receptors by Functionally Selective Modulators and Ligands.

Journal Article ACS Chem Biol · March 17, 2017 Nicotinic acetylcholine receptors regulate the nicotine dependence encountered with cigarette smoking, and this has stimulated a search for drugs binding the responsible receptor subtypes. Studies link a gene cluster encoding for α3β4α5-D398N nicotinic ace ... Full text Link to item Cite

Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

Journal Article EBioMedicine · March 2017 Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with infl ... Full text Open Access Link to item Cite

A Novel Phosphoregulatory Switch Controls the Activity and Function of the Major Catalytic Subunit of Protein Kinase A in Aspergillus fumigatus.

Journal Article mBio · February 7, 2017 UNLABELLED: Invasive aspergillosis (IA), caused by the filamentous fungal pathogen Aspergillus fumigatus, is a major cause of death among immunocompromised patients. The cyclic AMP/protein kinase A (PKA) signaling pathway is essential for hyphal growth and ... Full text Link to item Cite

Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.

Journal Article J Neurochem · February 2017 Vagal Nerve Stimulation (VNS) Therapy® is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are un ... Full text Link to item Cite

Identification of an elaborate complex mediating postsynaptic inhibition.

Journal Article Science · September 9, 2016 Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity- ... Full text Link to item Cite

Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

Journal Article PLoS Pathog · September 2016 Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substra ... Full text Open Access Link to item Cite

Proteomic Profiling Reveals Adaptive Responses to Surgical Myocardial Ischemia-Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats.

Journal Article Anesthesiology · June 2016 BACKGROUND: Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes that are characteristic of th ... Full text Link to item Cite

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.

Journal Article Gut · April 2016 OBJECTIVE: The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell ... Full text Open Access Link to item Cite

Identification of Proteins Bound to Dengue Viral RNA In Vivo Reveals New Host Proteins Important for Virus Replication.

Journal Article mBio · January 5, 2016 UNLABELLED: Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Due to the limited coding capacity of the viral genome and the complexity of the viral life cycle, host cell proteins play essential roles throughout the course of ... Full text Link to item Cite

Dephosphorylation of the Core Septin, AspB, in a Protein Phosphatase 2A-Dependent Manner Impacts Its Localization and Function in the Fungal Pathogen Aspergillus fumigatus.

Journal Article Front Microbiol · 2016 Septins are a conserved family of GTPases that form hetero-oligomeric complexes and perform diverse functions in higher eukaryotes, excluding plants. Our previous studies in the human fungal pathogen Aspergillus fumigatus revealed that the core septin, Asp ... Full text Link to item Cite

Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.

Journal Article EBioMedicine · November 2015 Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that ... Full text Link to item Cite

Hsp70 and the Cochaperone StiA (Hop) Orchestrate Hsp90-Mediated Caspofungin Tolerance in Aspergillus fumigatus.

Journal Article Antimicrob Agents Chemother · August 2015 Aspergillus fumigatus is the primary etiologic agent of invasive aspergillosis (IA), a major cause of death among immunosuppressed patients. Echinocandins (e.g., caspofungin) are increasingly used as second-line therapy for IA, but their activity is only f ... Full text Link to item Cite

The Aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.

Journal Article Fungal Genet Biol · August 2015 Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the human pathogenic yeasts Candida albicans and Cry ... Full text Link to item Cite

Calcium-Mediated Induction of Paradoxical Growth following Caspofungin Treatment Is Associated with Calcineurin Activation and Phosphorylation in Aspergillus fumigatus.

Journal Article Antimicrob Agents Chemother · August 2015 The echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of Aspergillus fumigatus, a phenomenon known as the "paradoxical effect," which is not consistently observed with other echinocandins (micafungin and anidula ... Full text Link to item Cite

Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.

Journal Article Genome Biol Evol · July 10, 2015 Although transcriptomic profiling has become the standard approach for exploring molecular differences in the primate brain, very little is known about how the expression levels of gene transcripts relate to downstream protein abundance. Moreover, it is un ... Full text Open Access Link to item Cite

Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

Journal Article J Proteome Res · February 6, 2015 The proteomic analysis of bronchoalveolar lavage fluid (BALF) can give insight into pulmonary disease pathology and response to therapy. Here, we describe the first gel-free quantitative analysis of BALF in idiopathic pulmonary fibrosis (IPF), a chronic an ... Full text Link to item Cite

Identification and mutational analyses of phosphorylation sites of the calcineurin-binding protein CbpA and the identification of domains required for calcineurin binding in Aspergillus fumigatus.

Journal Article Front Microbiol · 2015 Calcineurin is a key protein phosphatase required for hyphal growth and virulence in Aspergillus fumigatus, making it an attractive antifungal target. However, currently available calcineurin inhibitors, FK506 and cyclosporine A, are immunosuppressive, lim ... Full text Link to item Cite

Metabolic control of Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated caspase-2 suppression by the B55β/protein phosphatase 2A (PP2A).

Journal Article J Biol Chem · December 26, 2014 High levels of metabolic activity confer resistance to apoptosis. Caspase-2, an apoptotic initiator, can be suppressed by high levels of nutrient flux through the pentose phosphate pathway. This metabolic control is exerted via inhibitory phosphorylation o ... Full text Link to item Cite

Convergent transcriptional specializations in the brains of humans and song-learning birds.

Journal Article Science · December 12, 2014 Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and huma ... Full text Open Access Link to item Cite

Structure and DNA-binding traits of the transition state regulator AbrB.

Journal Article Structure · November 4, 2014 The AbrB protein from Bacillus subtilis is a DNA-binding global regulator controlling the onset of a vast array of protective functions under stressful conditions. Such functions include biofilm formation, antibiotic production, competence development, ext ... Full text Open Access Link to item Cite

Hydrolytic function of Exo1 in mammalian mismatch repair.

Journal Article Nucleic Acids Res · June 2014 Genetic and biochemical studies have previously implicated exonuclease 1 (Exo1) in yeast and mammalian mismatch repair, with results suggesting that function of the protein in the reaction depends on both its hydrolytic activity and its ability to interact ... Full text Link to item Cite

A DNA mimic: the structure and mechanism of action for the anti-repressor protein AbbA.

Journal Article J Mol Biol · May 1, 2014 Bacteria respond to adverse environmental conditions by switching on the expression of large numbers of genes that enable them to adapt to unfavorable circumstances. In Bacillus subtilis, many adaptive genes are under the negative control of the global tra ... Full text Open Access Link to item Cite

Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus.

Journal Article Antimicrob Agents Chemother · 2014 Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced Asp ... Full text Link to item Cite

Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.

Journal Article PLoS One · 2014 Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, ... Full text Link to item Cite

Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

Journal Article PLoS One · 2014 The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart fail ... Full text Open Access Link to item Cite

A flexible statistical model for alignment of label-free proteomics data--incorporating ion mobility and product ion information.

Journal Article BMC Bioinformatics · December 16, 2013 BACKGROUND: The goal of many proteomics experiments is to determine the abundance of proteins in biological samples, and the variation thereof in various physiological conditions. High-throughput quantitative proteomics, specifically label-free LC-MS/MS, a ... Full text Open Access Link to item Cite

Automated, reproducible, titania-based phosphopeptide enrichment strategy for label-free quantitative phosphoproteomics.

Journal Article J Biomol Tech · April 2013 An automated phosphopeptide enrichment strategy is described using titanium dioxide (TiO2)-packed, fused silica capillaries for use with liquid chromatography (LC)-mass spectrometry (MS)/MS-based, label-free proteomics workflows. To correlate an optimum pe ... Full text Link to item Cite

NADPH:quinone oxidoreductase 1 regulates host susceptibility to ozone via isoprostane generation.

Journal Article J Biol Chem · February 15, 2013 NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently repor ... Full text Link to item Cite

Filamentous fungal-specific septin AspE is phosphorylated in vivo and interacts with actin, tubulin and other septins in the human pathogen Aspergillus fumigatus.

Journal Article Biochem Biophys Res Commun · February 15, 2013 We previously analyzed the differential localization patterns of five septins (AspA-E), including a filamentous fungal-specific septin, AspE, in the human pathogen Aspergillus fumigatus. Here we utilized the A. fumigatus strain expressing an AspE-EGFP fusi ... Full text Link to item Cite

Application of a label-free, gel-free quantitative proteomics method for ecotoxicological studies of small fish species.

Journal Article Environ Sci Technol · January 15, 2013 Although two-dimensional electrophoresis (2D-GE) remains the basis for many ecotoxicoproteomic analyses, newer non-gel-based methods are beginning to be applied to overcome throughput and coverage limitations of 2D-GE. The overall objective of our research ... Full text Link to item Cite

Proteomic analysis of ERK1/2-mediated human sickle red blood cell membrane protein phosphorylation.

Journal Article Clin Proteomics · January 3, 2013 BACKGROUND: In sickle cell disease (SCD), the mitogen-activated protein kinase (MAPK) ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs). ERK1/2 is involved in activatio ... Full text Open Access Link to item Cite

Phosphorylation of Calcineurin at a novel serine-proline rich region orchestrates hyphal growth and virulence in Aspergillus fumigatus.

Journal Article PLoS Pathog · 2013 The fungus Aspergillus fumigatus is a leading infectious killer in immunocompromised patients. Calcineurin, a calmodulin (CaM)-dependent protein phosphatase comprised of calcineurin A (CnaA) and calcineurin B (CnaB) subunits, localizes at the hyphal tips a ... Full text Link to item Cite

Role of unusual P loop ejection and autophosphorylation in HipA-mediated persistence and multidrug tolerance.

Journal Article Cell Rep · September 27, 2012 HipA is a bacterial serine/threonine protein kinase that phosphorylates targets, bringing about persistence and multidrug tolerance. Autophosphorylation of residue Ser150 is a critical regulatory mechanism of HipA function. Intriguingly, Ser150 is not loca ... Full text Link to item Cite

Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.

Journal Article Sci Signal · July 17, 2012 Chemokine signaling is critical for T cell function during homeostasis and inflammation and directs T cell polarity and migration through the activation of specific intracellular pathways. Here, we uncovered a previously uncharacterized role for the Abl fa ... Full text Link to item Cite

The protein expression landscape of the Arabidopsis root.

Journal Article Proc Natl Acad Sci U S A · May 1, 2012 Because proteins are the major functional components of cells, knowledge of their cellular localization is crucial to gaining an understanding of the biology of multicellular organisms. We have generated a protein expression map of the Arabidopsis root pro ... Full text Link to item Cite

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

Journal Article Blood · February 2, 2012 The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is funct ... Full text Link to item Cite

Peptide array X-linking (PAX): a new peptide-protein identification approach.

Journal Article PLoS One · 2012 Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Arr ... Full text Link to item Cite

SH3 domain-based phototrapping in living cells reveals Rho family GAP signaling complexes.

Journal Article Sci Signal · November 29, 2011 Rho family GAPs [guanosine triphosphatase (GTPase) activating proteins] negatively regulate Rho family GTPase activity and therefore modulate signaling events that control cytoskeletal dynamics. The spatial distribution of these GAPs and their specificity ... Full text Link to item Cite

Quantitative label-free phosphoproteomics strategy for multifaceted experimental designs.

Journal Article Anal Chem · May 15, 2011 Protein phosphorylation is a critical regulator of signaling in nearly all eukaryotic cellular pathways and dysregulated phosphorylation has been implicated in an array of diseases. The majority of MS-based quantitative phosphorylation studies are currentl ... Full text Link to item Cite

Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis.

Journal Article Infect Immun · October 2010 Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we h ... Full text Link to item Cite

Mass spectrometry-based thermal shift assay for protein-ligand binding analysis.

Journal Article Anal Chem · July 1, 2010 Described here is a mass spectrometry-based screening assay for the detection of protein-ligand binding interactions in multicomponent protein mixtures. The assay utilizes an oxidation labeling protocol that involves using hydrogen peroxide to selectively ... Full text Open Access Link to item Cite

Characterization of a new family of protein kinases from Arabidopsis containing phosphoinositide 3/4-kinase and ubiquitin-like domains.

Journal Article Biochem J · January 1, 2008 At least two of the genes predicted to encode type II PI4K (phosphoinositide 4-kinase) in Arabidopsis thaliana (thale cress), namely AtPI4Kgamma4 and AtPI4Kgamma7, encode enzymes with catalytic properties similar to those of members of the PIKK (phosphoino ... Full text Link to item Cite

Location and role of free cysteinyl residues in the Sindbis virus E1 and E2 glycoproteins.

Journal Article J Virol · June 2007 Sindbis virus is a single-stranded positive-sense RNA virus. It is composed of 240 copies of three structural proteins: E1, E2, and capsid. These proteins form a mature virus particle composed of two nested T=4 icosahedral shells. A complex network of disu ... Full text Link to item Cite

Tandem mass spectrometry acquisition approaches to enhance identification of protein-protein interactions using low-energy collision-induced dissociative chemical crosslinking reagents.

Journal Article Rapid Commun Mass Spectrom · 2007 Chemical crosslinking combined with mass spectrometry is a useful tool for studying the topological organization of multiprotein interactions, but it is technically challenging to identify peptides involved in a crosslink using tandem mass spectrometry (MS ... Full text Link to item Cite

Collision-induced dissociative chemical cross-linking reagents and methodology: Applications to protein structural characterization using tandem mass spectrometry analysis.

Journal Article Anal Chem · December 1, 2006 Chemical cross-linking combined with mass spectrometry is a viable approach to study the low-resolution structure of protein and protein complexes. However, unambiguous identification of the residues involved in a cross-link remains analytically challengin ... Full text Link to item Cite

A mass spectrometry-based proteomic approach to study Marek's Disease Virus gene expression.

Journal Article J Virol Methods · July 2006 Marek's Disease Virus (MDV) is an avian herpesvirus that causes a lymphoproliferative disorder in chickens. MDV transitions between a lytic phase in which new viruses are produced and a latent phase in which the virus lays dormant. The mechanism controllin ... Full text Link to item Cite

Novel protein purification system utilizing an N-terminal fusion protein and a caspase-3 cleavable linker.

Journal Article Protein Expr Purif · May 2006 Coupled with over-expression in host organisms, fusion protein systems afford economical methods to obtain large quantities of target proteins in a fast and efficient manner. Some proteases used for these purposes cleave C-terminal to their recognition seq ... Full text Link to item Cite

Identification and functional analysis of in vivo phosphorylation sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 receptor kinase.

Journal Article Plant Cell · June 2005 Brassinosteroids (BRs) regulate multiple aspects of plant growth and development and require an active BRASSINOSTEROID-INSENSITIVE1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1) for hormone perception and signal transduction. Many animal receptor kina ... Full text Link to item Cite