A5010242048- Cancer, Hypoxia, and Metabolism
- High Altitude and Hypoxia
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- Mitochondrial Function and Pathology
- Pregnancy and preeclampsia studies
- Adipose Tissue and Metabolism
- NF-κB Signaling Pathways
- Blood Coagulation and Thrombosis Mechanisms
- Adrenal and Paraganglionic Tumors
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Metabolomics and Mass Spectrometry Studies
- Erythropoietin and Anemia Treatment
- Hemoglobinopathies and Related Disorders
- Immune Response and Inflammation
- Metalloenzymes and iron-sulfur proteins
- Cancer-related gene regulation
- Advanced Proteomics Techniques and Applications
- Protein Tyrosine Phosphatases
- Complement system in diseases
- Orthopedic Surgery and Rehabilitation
- Hydrogen Storage and Materials
- Cancer Genomics and Diagnostics
California University of Pennsylvania
2020-2025
Hospital of the University of Pennsylvania
2024
University of Pennsylvania
2013-2023
Genapsys (United States)
2019
National Heart Lung and Blood Institute
2018
Mallinckrodt (United States)
2018
National Institutes of Health
2018
University of Colorado Anschutz Medical Campus
2018
Stanford University
2018
St. Louis Children's Hospital
2018
Hypoxia-inducible factor-1α (HIF-1α) 1 is a global transcriptional regulator of the hypoxic response. Under normoxic conditions, HIF-1α recognized by von Hippel-Lindau tumor-suppressor protein (VHL), component an E3 ubiquitin ligase complex. This interaction thereby promotes rapid degradation HIF-1α. stabilized. We have previously shown that VHL binds in hypoxia-sensitive manner to 27-aa segment HIF-1α, and this regulation depends on posttranslational modification Through combination vivo...
The number of red blood cells is normally tightly regulated by a classic homeostatic mechanism based on oxygen sensing in the kidney. Decreased delivery resulting from anemia induces production erythropoietin, which increases cell and hence delivery. Investigations erythropoietin regulation identified transcription factor hypoxia-inducible (HIF). HIF now recognized as being key regulator genes that function comprehensive range processes besides erythropoiesis, including energy metabolism...
Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of supply and demand oxygen throughout body. HIF-alpha a transcription that modulates wide range processes, including erythropoiesis, angiogenesis, cellular metabolism. We describe family with erythrocytosis mutation in HIF2A gene, encodes HIF-2alpha protein. Our functional studies indicate this leads stabilization protein suggest wild-type regulates erythropoietin production adults.
A critical step in the signal-induced activation of transcription factor NF-kappaB is site-specific phosphorylation its inhibitor, IkappaB, that targets latter for degradation by ubiquitin-proteasome pathway. We have previously shown mitogen-activated protein kinase/ERK kinase 1 (MEKK1) can induce both this IkappaB alpha at Ser-32 and Ser-36 vivo activity a high molecular weight complex vitro. Subsequently, others identified two proteins, (IKK-alpha) beta (IKK-beta), are present tumor...
Journal Article Calculations of antibody-antigen interactions: microscopic and semi-microscopic evaluation the free energies binding phosphorylcholine analogs to McPC603 Get access Frederick S. Lee, Lee Department Chemistry, University Sothern CaliforniaLos Angeles, CA 90089-1062 Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhen-Tao Chu, Chu Michael B. Bolger, Bolger 1Department Pharmaceutical Science, Southren 90033, USA Arieh Warshel Protein Engineering,...
Hypoxia-inducible factor (HIF) is a heterodimeric transcription induced by hypoxia. Under normoxic conditions, site-specific proline hydroxylation of the alpha subunits HIF allows recognition von Hippel-Lindau tumor suppressor protein (VHL), component an E3 ubiquitin ligase complex that targets these for degradation ubiquitin-proteasome pathway. hypoxic this inhibited, allowing to escape VHL-mediated degradation. Three enzymes, prolyl hydroxylase domain-containing proteins 1, 2, and 3 (PHD1,...
Recent evidence indicates that nuclear factor-κB (NF-κB), a transcription factor critically important for immune and inflammatory responses, is activated by protein kinase cascade. The essential features of this cascade are mitogen-activated (MAP3K) activates an IκB (IKK) site-specifically phosphorylates IκB. protein, which ordinarily sequesters NF-κB in the cytoplasm, subsequently degraded ubiquitin-proteasome pathway, thereby allowing translocation NF-κB. Thus far, only two MAP3Ks, NIK...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTight-binding inhibition of angiogenin and ribonuclease A by placental inhibitorFrank S. Lee, Robert Shapiro, Bert L. ValleeCite this: Biochemistry 1989, 28, 1, 225–230Publication Date (Print):January 10, 1989Publication History Published online1 May 2002Published inissue 10 January 1989https://pubs.acs.org/doi/10.1021/bi00427a031https://doi.org/10.1021/bi00427a031research-articleACS PublicationsRequest reuse permissionsArticle...
The central pathway for oxygen-dependent control of red cell mass is the prolyl hydroxylase domain protein (PHD):hypoxia inducible factor (HIF) pathway. PHD site specifically hydroxylates transcription HIF-α, thereby targeting latter degradation. Under hypoxia, this modification attenuated, allowing stabilized HIF-α to activate target genes, including that erythropoietin (EPO). Studies employing genetically modified mice point Hif-2α, one two main Hif-α isoforms, as being critical regulator...
Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO 2 max) altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans natural selection nominated Egl-9 homolog 1 gene ( EGLN1 ) as candidate gene. The encoded protein, EGLN1/PHD2, is an O sensor that controls levels the Hypoxia Inducible Factor-α (HIF-α), regulates cellular response From GW association and analysis covariance performed on total sample...
Transgenic mice harboring the int-2/Fgf-3 protooncogene under transcriptional control of mouse mammary tumor virus (MMTV) promoter/enhancer exhibit a dramatic, benign hyperplasia gland. In one int-2 transgenic line (TG.NX), this growth disturbance is evoked by pregnancy and regresses after parturition. Regression hyperplastic epithelium less complete successive pregnancies, and, within 10 months, most TG.NX stochastically develop carcinomas that are transplantable in virgin, syngeneic mice....
Prolyl hydroxylase domain protein 2 (PHD2, also known as Egg Laying Defective Nine homolog 1) is a key oxygen-sensing in metazoans. In an oxygen-dependent manner, PHD2 site-specifically prolyl hydroxylates the master transcription factor of hypoxic response, hypoxia-inducible factor-α (HIF-α), thereby targeting HIF-α for degradation. this report we show that heat shock 90 (HSP90) co-chaperones p23 and FKBP38 interact via conserved Pro-Xaa-Leu-Glu motif (where Xaa = any amino acid) these...
The schuhli nut is a device designed to lock an AO 4.5-mm cortical screw dynamic compression plate independent of bony contact with the plate. engages below plate, elevating and locking at 90° angle, thus preventing toggling. Photoelastic modeling biomechamical testing on sheep tibias were done determine mechanical properties constructs using nuts. Use nuts was shown decrease stress in bone initial axial stiffness construct fixed less than standard screws, but rate loss cyclic loading...