A5102727449- Ion Transport and Channel Regulation
- Magnesium in Health and Disease
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Ion channel regulation and function
- Zebrafish Biomedical Research Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Hydrogen Storage and Materials
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Marine Invertebrate Physiology and Ecology
- Acute Kidney Injury Research
- Electrolyte and hormonal disorders
- Adenosine and Purinergic Signaling
- Metabolism, Diabetes, and Cancer
- Aquaculture disease management and microbiota
- Metabolomics and Mass Spectrometry Studies
- Angiogenesis and VEGF in Cancer
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Potassium and Related Disorders
- Diet, Metabolism, and Disease
- Hormonal Regulation and Hypertension
- Marine Sponges and Natural Products
- Retinal Diseases and Treatments
Oregon Health & Science University
2017-2024
Ohio Northern University
2012
Significance Intestinal epithelial barrier dysregulation is a hallmark of inflammatory bowel diseases (IBDs). A central role for hypoxic signaling has been defined in modulation during inflammation. We demonstrate that genes involved creatine metabolism, the kinases (CKs), are coordinately regulated by hypoxia-inducible transcription factors (HIFs) and such regulation critical to function. Inhibition CK pathway abrogates apical junction assembly integrity. Dietary supplementation profoundly...
Article22 June 2020Open Access Transparent process Identification and characterization of diverse OTU deubiquitinases in bacteria Alexander F Schubert orcid.org/0000-0002-1834-3787 Medical Research Council Laboratory Molecular Biology, Cambridge, UK Search for more papers by this author Justine V Nguyen orcid.org/0000-0001-9739-5261 Department Microbiology & Immunology, Oregon Health Science University, Portland, OR, USA Tyler G Franklin orcid.org/0000-0002-0311-1190 Paul P Geurink...
Mutations in the ubiquitin ligase scaffold protein Cullin 3 (CUL3) cause disease familial hyperkalemic hypertension (FHHt). In kidney, mutant CUL3 (CUL3-Δ9) increases abundance of With-No-Lysine [K] Kinase 4 (WNK4), with excessive activation downstream Sterile 20 (STE20)/SPS-1-related proline/alanine-rich kinase (SPAK) increasing phosphorylation Na+-Cl- cotransporter (NCC). CUL3-Δ9 promotes its own degradation via autoubiquitination, leading to hypothesis that Cul3 haploinsufficiency causes...
K+ deficiency stimulates renal salt reuptake via the Na+-Cl- cotransporter (NCC) of distal convoluted tubule (DCT), thereby reducing losses in downstream nephron segments while increasing NaCl retention and blood pressure. NCC activation is mediated by a kinase cascade involving with no lysine (WNK) kinases upstream Ste20-related proline-alanine-rich (SPAK) oxidative stress-responsive kinase-1 (OSR1). In deficiency, WNKs SPAK/OSR1 concentrate spherical cytoplasmic domains DCT termed "WNK...
Peripheral sensory neurons are a critical part of the nervous system that transmit multitude stimuli to central system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory (RBs). RBs optically accessible amenable experimental manipulation, making them powerful for mechanistic investigation neurons. Previous studies provided evidence fall into multiple subclasses; however, number molecular make up these potential RB subtypes have not been...
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along distal convoluted tubule, an effect central phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels connecting collecting tubules have also been documented, WNK4 typically believed little role in modulating chloride reabsorption thick ascending limb loop Henle. Yet wnk4-/- mice (knockout lacking WNK4) do not demonstrate hypocalciuria typical...
Significance Statement Familial hyperkalemic hypertension (FHHt) results from inappropriate activation of the Na + Cl – cotransporter (NCC). Causative mutations have been identified in gene encoding Cullin3 (CUL3). with substrate binding adaptor Kelch-like 3 (KLHL3) forms an E3 ubiquitin ligase that mediates degradation NCC regulatory kinases. The mechanism by which mutant CUL3 causes FHHt is unclear, but lower abundance and KLHL3 proteins loss to regulator JAB1 implicated. Using several...
Hypomagnesemia is associated with reduced kidney function and life-threatening complications sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg 2+ excretion and, via activity of the Na + -Cl − cotransporter (NCC), also plays a key role in K homeostasis by metering delivery to segments. Little known about mechanisms which plasma concentration regulates NCC how low-plasma interact modulate activity. To address this, we performed dietary manipulation studies...
ABSTRACT Peripheral sensory neurons are a critical part of the nervous system that transmit multitude stimuli to central system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory (RBs). RBs optically accessible amenable experimental manipulation, making them powerful for mechanistic investigation neurons. Previous studies provided evidence fall into multiple subclasses; however, number molecular make up these potential RB subtypes have not...
The distal nephron is essential for calcium homeostasis. This evidenced by disordered transport following disrupted function occurring in salt-wasting tubulopathies or with diuretic use. A plethora of studies support a role WNK4 thick ascending limb (TAL) and convoluted tubule ion most focusing on sodium transport. Little known about the vivo regulating homeostsis. Here, we investigated using knockout animals (WNK4-/- ). As has been shown previously, found that baseline urinary levels are...
NF-κB is an evolutionarily conserved eukaryotic transcription factor that plays a role in many important developmental and immune-related processes by activating target gene expression. The goal of these experiments was to define the sequences required for sea anemone NF-κB's intrinsic transactivation activity using mutant proteins with serial deletions N- C-terminal sequences. Deletion mutants were constructed missing 15, 32 or 47 amino acids (aa) N-terminal 17, 27 aa 440 protein from...
ABSTRACT Manipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing signals, for example, invading pathogens can inactivate immune response pathways evade detection. The Ovarian Tumor (OTU) family deubiquitinases regulates diverse signals in humans. Viral have also extensively co-opted the OTU fold to subvert signaling, but extent which bacteria utilize was unknown. We predicted validated a set encoded...
Endothelial cell proliferation is required for angiogenesis. Our laboratory has previously shown that activation of the A2B adenosine receptor (A2BAR) through cAMP effector Epac1 activates extracellular signal‐regulated kinase (ERK1/2), a key protein endothelial proliferation. Presently, we hypothesize small GTPase Rac1 involved in signaling from A2BAR and to ERK1/2 activation. In human microvascular cells (HMVEC), Rac inhibitor NSC23766 diminished by agonist 5‐N‐ethylcarboxamidoadenosine...