The long-term objective of the Physician-Scientist Award is for the principal investigator to prepare for a career as an independent researcher in the biomedical sciences through five years of basic science training. Phase I will consist of intensive training in molecular and cell biology which will be primarily accomplished through work on a research project in the Laboratory of Cell Biology at Rockefeller University. Specifically, the project will be concerned with characterization of protein components of the nuclear pore complex, an organelle involved in the transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells. Pore complex proteins will be purified by monoclonal antibody affinity chromatography with antibodies found to inhibit macromolecule transport across the nuclear envelope of isolated nuclei. Polyclonal antibodies will be raised against these purified proteins and oligonucleotide probes will be synthesized complementary to the determined amino acid sequences of fragments if these proteins. The polyclonal antibodies and oligonucleotide probes will be used to screen cDNA libraries to islolate clones encoding pore complex proteins. The cDNA clones will be sequenced to obtain the entire amino acid sequences of the pore complex proteins. Such information should provide a better understanding of the role of the nuclear pore complex in the selective transport of macromolecules across the nuclear envelope. In Phase II of the Award, research will be conducted in the Department of Medicine at Cornell University Medical College. Methodology learned during Phase I will be used to characterize membrane bound proteins of hepatocytes or intestinal epithelial cells. Such proteins are involved in physiological functions ranging from billirubin metabolism to ion transport, and these proteins may be defective in various disease states. Characterization of membrane bound proteins of hepatic or intestinal cells at the molecular level should provide a better understanding of their functions in normal physiology and possible dysfunction in disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Physician Scientist Award (K11)
Project #
7K11DK001790-04
Application #
3086380
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Hytiroglou, P; Choi, S W; Theise, N D et al. (1993) The expression of nuclear lamins in human liver: an immunohistochemical study. Hum Pathol 24:169-72
Soullam, B; Worman, H J (1993) The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal. J Cell Biol 120:1093-100
Courvalin, J C; Segil, N; Blobel, G et al. (1992) The lamin B receptor of the inner nuclear membrane undergoes mitosis-specific phosphorylation and is a substrate for p34cdc2-type protein kinase. J Biol Chem 267:19035-8
Dannenberg, A J; Worman, H J; Scarlata, S (1992) Developmental changes in the amount and functional state of UDP-glucuronosyltransferase. Biochim Biophys Acta 1116:250-5
Worman, H J; Ip, J H; Winters, S L et al. (1992) Hypersensitivity reaction associated with acute hepatic dysfunction following a single intravenous dose of procainamide. J Intern Med 232:361-3
Berk, P D; Worman, H J (1992) An introduction to molecular biology and recombinant DNA technology for the hepatologist. Semin Liver Dis 12:227-45
Worman, H J; Courvalin, J C (1991) Autoantibodies against nuclear envelope proteins in liver disease. Hepatology 14:1269-79
Courvalin, J C; Lassoued, K; Worman, H J et al. (1990) Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J Exp Med 172:961-7
Worman, H J (1990) Cellular intermediate filament networks and their derangement in alcoholic hepatitis. Alcohol Clin Exp Res 14:789-804
Worman, H J; Evans, C D; Blobel, G (1990) The lamin B receptor of the nuclear envelope inner membrane: a polytopic protein with eight potential transmembrane domains. J Cell Biol 111:1535-42

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