A group of several independent scientists at The University of Chicago seeks to create a coordinated program in sickle cell disease research. Their approaches vary widely, but they share a common interest: the erythrocyte in health and disease, sickle cell disease in particular.
Their aims are to draw closer together around the topic of sickle cell disease; to create a highly interactive scientific group whose diverse interests will be synergistic; to foster new and better research, both individual and collaborative; and to expedite such research through coordinated sharing of scientific information, instrumentation, core facilities, patients, and data. The benefits of the program project will be the promotion of mutual education, new scientific insights, improved collaboration, and increased efficiency and economy of research through a central focus on sickle cell disease. This application seeks support for this program. The theme of this program is the biology of the erythrocyte in sickle cell disease. In that the research emanates from independent scientific programs, it is not unitary but diverse and complementary. The program thus draws strength from the breadth of its membership and a wide range of expertise. There is, nevertheless, considerable continuity in the scope of the research. Huttenlocher seeks to relieve the occlusive cerebral vascular disease arising from the compromised rheology of sickled cells. Shen proposes to elucidate the structural basis for the irreversibly-sickled cell; an altered sub-membrane filamentous network. Josephs will continue his characterization of hemoglobin S fibers by high resolution electron microscopy. Potel will apply computer techniques to the analysis of Josephs's EM data and Huttenlocher's positron emission tomographs. Steck will test a novel hypothesis which explains and promises to reverse the increased passive permeability of sickle cell membranes to small solutes. Goldwasser will study the expression of globin genes and Gross will study the control of their translation. Not all projects interact with all others; this would be an unrealistic goal for research programs that originate with investigators rather than with a single organizer. There is, however, a stong element of mutual interest that is bound to help advance the science in each subproject.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL030121-14
Application #
2430632
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1988-12-01
Project End
1999-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Chicago
Department
Biochemistry
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Cassady, Kevin A; Gross, Martin (2002) The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain. J Virol 76:2029-35
Gupta, M; Mungai, P T; Goldwasser, E (2000) A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene. Blood 96:491-7
Kung, C; Fan, L; Goldwasser, E (2000) The role of tyrosine 15 in erythropoietin action. Arch Biochem Biophys 379:85-9
Gross, M; Hessefort, S; Olin, A (1999) Purification of a 38-kDa protein from rabbit reticulocyte lysate which promotes protein renaturation by heat shock protein 70 and its identification as delta-aminolevulinic acid dehydratase and as a putative DnaJ protein. J Biol Chem 274:3125-34
Cassady, K A; Gross, M; Roizman, B (1998) The second-site mutation in the herpes simplex virus recombinants lacking the gamma134.5 genes precludes shutoff of protein synthesis by blocking the phosphorylation of eIF-2alpha. J Virol 72:7005-11
Cassady, K A; Gross, M; Roizman, B (1998) The herpes simplex virus US11 protein effectively compensates for the gamma1(34.5) gene if present before activation of protein kinase R by precluding its phosphorylation and that of the alpha subunit of eukaryotic translation initiation factor 2. J Virol 72:8620-6
He, B; Gross, M; Roizman, B (1998) The gamma134.5 protein of herpes simplex virus 1 has the structural and functional attributes of a protein phosphatase 1 regulatory subunit and is present in a high molecular weight complex with the enzyme in infected cells. J Biol Chem 273:20737-43
He, B; Gross, M; Roizman, B (1997) The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activa Proc Natl Acad Sci U S A 94:843-8
Picot, D; Loll, P J; Garavito, R M (1997) X-ray crystallographic study of the structure of prostaglandin H synthase. Adv Exp Med Biol 400A:107-11
Goldwasser, E (1996) Erythropoietin: a somewhat personal history. Perspect Biol Med 40:18-32

Showing the most recent 10 out of 62 publications