Research Topics
Species | Frank LeeSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylationMelanie J Percy
Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB, UK
Mol Cancer 2:31. 2003..The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE)...
The HIF pathway and erythrocytosisFrank S Lee
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Annu Rev Pathol 6:165-92. 2011..Rare patients with erythrocytosis have mutations in the genes encoding for PHD2, HIF-2α, and VHL, which implicates these proteins as critical to the proper control of red blood cell mass in humans...- Oxygen sensing: recent insights from idiopathic erythrocytosisFrank S Lee
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Cell Cycle 5:941-5. 2006..A recent report of familial erythrocytosis now implicates a different protein, Prolyl Hydroxylase Domain protein 2 (PHD2), which is an enzyme that hydroxylates HIF... - Genetic causes of erythrocytosis and the oxygen-sensing pathwayFrank S Lee
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 605 Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA
Blood Rev 22:321-32. 2008.... 
Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transferSteven E Raper
Department of Surgery, University of Pennsylvania School of Medicine, BRB II III Rm, 607 421 Curie Blvd, Philadelphia, PA 19104, USA
Mol Genet Metab 80:148-58. 2003....- Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging miceXiping Li
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Blood Cells Mol Dis 45:9-19. 2010..Conversely, other Hif targets, including Vegf, Pgk1, and Phd3 are upregulated in the liver but not in the kidney in both age groups. These findings have implications for targeting this pathway in the aging... - Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor prolinePaul W Furlow
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 284:9050-8. 2009.... - Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3Jianhe Huang
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 277:39792-800. 2002..Thus, these results provide evidence that the only obligatory residue for proline hydroxylation in HIF-1alpha is the hydroxylacceptor proline itself... - A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasisMelanie J Percy
Department of Haematology, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland, United Kingdom
Proc Natl Acad Sci U S A 103:654-9. 2006..Our findings indicate that PHD2 is critical for normal regulation of HIF in humans... - A gain-of-function mutation in the HIF2A gene in familial erythrocytosisMelanie J Percy
Belfast City Hospital, Northern Ireland, United Kingdom
N Engl J Med 358:162-8. 2008..Our functional studies indicate that this mutation leads to stabilization of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults... - Novel exon 12 mutations in the HIF2A gene associated with erythrocytosisMelanie J Percy
Department of Haematology, Belfast City Hospital, Belfast, United Kingdom
Blood 111:5400-2. 2008..These findings support the importance of HIF-2 alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis... - A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding grooveMelanie J Percy
Department of Haematology, Belfast City Hospital, Belfast, United Kingdom
Blood 110:2193-6. 2007..These findings substantiate PHD2 as a critical enzyme controlling HIF and therefore Epo in humans, and furthermore suggest the location of an active site groove in PHD2 that binds HIF... - Familial erythrocytosis: molecular links to red blood cell controlMelanie J Percy
Haematologica 93:963-7. 2008 - A novel beta-oxa polyunsaturated fatty acid downregulates the activation of the IkappaB kinase/nuclear factor kappaB pathway, inhibits expression of endothelial cell adhesion molecules, and depresses inflammationAntonio Ferrante
Department of Immunopathology, Women s and Children s Hospital, University of Adelaide, South Australia, Australia
Circ Res 99:34-41. 2006..These novel PUFAs could form the basis for a potential new class of pharmaceuticals for treating inflammatory diseases, including atherosclerosis... - Regulation of adult erythropoiesis by prolyl hydroxylase domain proteinsKotaro Takeda
Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 3501, USA
Blood 111:3229-35. 2008..These findings suggest that PHD1/3 double deficiency leads to erythrocytosis partly by activating the hepatic HIF-2alpha/Epo pathway, whereas PHD2 deficiency leads to erythrocytosis by activating the renal Epo pathway...
Research Grants
- Molecular Mechanisms of the Hypoxic ResponseFrank S Lee; Fiscal Year: 2010..The proposed experiments will have implications for treating diseases such as anemia, in which red blood cell mass is abnormally low. ..
- A Novel Regulator of Oxygen HomeostasisFrank Lee; Fiscal Year: 2009..We anticipate that these studies will define a new pathway by which cells respond to hypoxia. ..
- A Novel Regulator of Oxygen HomeostasisFrank Lee; Fiscal Year: 2007..We anticipate that these studies will define a new pathway by which cells respond to hypoxia. ..
- Molecular Mechanisms of the Hypoxic ResponseFrank Lee; Fiscal Year: 2006..We anticipate that the proposed studies will enlarge our understanding of both the molecular response to hypoxia and the role of a novel postranslational modification--proline hydroxylation. ..
- PATHOPHYSIOLOGY OF RENAL TUBULAR CELLSFrank Lee; Fiscal Year: 2002....
- The HydroxylprolylproteomeFrank S Lee; Fiscal Year: 2010..These studies will have implications for understanding diseases such as heart attacks, stroke, and cancer, because they are characterized by hypoxia. ..