Abstract

The main objective of this project is to improve our understanding of the hypoxia sensing by delineation of the molecular pathology of a congenital defect of this pathway that leads to a constitutive upregulation of the hypoxia sensing-Chuvash polycythemia (CP). Hypoxic sensing is an essential physiological mechanism that developed in mammals that control many important physiological and developmental processes including regulation of erythropoiesis. A gene that leads to a disease phenotype must be involved in an important, non-redundant physiological control point. Thus, the identification of the gene causing CP will improve our understanding of hypoxia sensing. The proposed research has the following specific aims:
Aim 1) Define the phenotype of CP;
Aim 2) Examine the in vitro growth of erythroid CP progenitors and elucidate the CP functional defect under intermittent hypoxic conditions;
and Aim 3) Map and isolate the CP gene and determine its mutation(s) leading to CP phenotype.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066333-02
Application #
6391213
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Program Officer
Evans, Gregory
Project Start
2000-09-30
Project End
2004-08-31
Budget Start
2001-09-30
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$261,625
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Yoon, Donghoon; Okhotin, David V; Kim, Bumjun et al. (2010) Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1alpha and HIF-2alpha. J Mol Med (Berl) 88:523-30
Sergueeva, Adelina I; Miasnikova, Galina Y; Okhotin, Daniel J et al. (2008) Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation. Haematologica 93:279-82
Agarwal, Neeraj; Gordeuk, Victor R; Prchal, Josef T (2007) Are erythropoietin receptors expressed in tumors? Facts and fiction--more careful studies are needed. J Clin Oncol 25:1813-4;author reply 1815
Bushuev, Vladimir I; Miasnikova, Galina Y; Sergueeva, Adelina I et al. (2006) Endothelin-1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. Haematologica 91:744-9
Gordeuk, Victor R; Prchal, Josef T (2006) Vascular complications in Chuvash polycythemia. Semin Thromb Hemost 32:289-94
Gordeuk, Victor R; Stockton, David W; Prchal, Josef T (2005) Congenital polycythemias/erythrocytoses. Haematologica 90:109-16
Mejia, Olga M; Prchal, Josef T; Leon-Velarde, Fabiola et al. (2005) Genetic association analysis of chronic mountain sickness in an Andean high-altitude population. Haematologica 90:13-9
Bento, Maria Celeste; Chang, Ko Tung; Guan, Yongli et al. (2005) Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: five new Caucasian patients. Haematologica 90:128-9
Prchal, Josef T (2005) Polycythemia vera and other primary polycythemias. Curr Opin Hematol 12:112-6
Gordeuk, Victor R; Sergueeva, Adelina I; Miasnikova, Galina Y et al. (2004) Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood 103:3924-32

Showing the most recent 10 out of 18 publications