Frank Lee

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation
    Melanie J Percy
    Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB, UK
    Mol Cancer 2:31. 2003
  2. doi request reprint The HIF pathway and erythrocytosis
    Frank S Lee
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Annu Rev Pathol 6:165-92. 2011
  3. pmc Oxygen sensing: recent insights from idiopathic erythrocytosis
    Frank S Lee
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell Cycle 5:941-5. 2006
  4. pmc Genetic causes of erythrocytosis and the oxygen-sensing pathway
    Frank 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
  5. ncbi request reprint Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
    Steven 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
  6. pmc Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging mice
    Xiping 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
  7. pmc Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline
    Paul 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
  8. pmc Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3
    Jianhe Huang
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:39792-800. 2002
  9. pmc A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis
    Melanie 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
  10. pmc A gain-of-function mutation in the HIF2A gene in familial erythrocytosis
    Melanie J Percy
    Belfast City Hospital, Northern Ireland, United Kingdom
    N Engl J Med 358:162-8. 2008

Research Grants

  1. Molecular Mechanisms of the Hypoxic Response
    Frank S Lee; Fiscal Year: 2010
  2. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2009
  3. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2007
  4. Molecular Mechanisms of the Hypoxic Response
    Frank Lee; Fiscal Year: 2006
  5. PATHOPHYSIOLOGY OF RENAL TUBULAR CELLS
    Frank Lee; Fiscal Year: 2002
  6. The Hydroxylprolylproteome
    Frank S Lee; Fiscal Year: 2010

Collaborators

Detail Information

Publications15

  1. pmc A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation
    Melanie 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)...
  2. doi request reprint The HIF pathway and erythrocytosis
    Frank 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...
  3. pmc Oxygen sensing: recent insights from idiopathic erythrocytosis
    Frank 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...
  4. pmc Genetic causes of erythrocytosis and the oxygen-sensing pathway
    Frank 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
    ....
  5. ncbi request reprint Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
    Steven 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
    ....
  6. pmc Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging mice
    Xiping 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...
  7. pmc Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline
    Paul 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
    ....
  8. pmc Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3
    Jianhe 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...
  9. pmc A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis
    Melanie 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...
  10. pmc A gain-of-function mutation in the HIF2A gene in familial erythrocytosis
    Melanie 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...
  11. pmc Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis
    Melanie 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...
  12. pmc A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
    Melanie 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...
  13. doi request reprint Familial erythrocytosis: molecular links to red blood cell control
    Melanie J Percy
    Haematologica 93:963-7. 2008
  14. ncbi request reprint 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 inflammation
    Antonio 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...
  15. pmc Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins
    Kotaro 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 Grants16

  1. Molecular Mechanisms of the Hypoxic Response
    Frank 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. ..
  2. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2009
    ..We anticipate that these studies will define a new pathway by which cells respond to hypoxia. ..
  3. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2007
    ..We anticipate that these studies will define a new pathway by which cells respond to hypoxia. ..
  4. Molecular Mechanisms of the Hypoxic Response
    Frank 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. ..
  5. PATHOPHYSIOLOGY OF RENAL TUBULAR CELLS
    Frank Lee; Fiscal Year: 2002
    ....
  6. The Hydroxylprolylproteome
    Frank 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. ..