Research: The broad spectrum of VIP biological functions are mediated by its receptor. In the lung, VIP acts as a potent smooth muscle relaxant and it may also regulate lung cancer proliferation. The long-term goal of this proposal is to determine molecular mechanisms that regulate VIP receptor expression during development and in disease.
The specific aims are to isolate and characterized the rat VIP receptor gene (2). Identity regulatory elements and factors that control VIP receptor transcription in both normal and cancerous lung cells transfection and DNA-protein binding assays (3). Study the regulation of VIP receptor expression during development by in situ hybridization and by homologous recombination to generate mice that lack functional VIP receptors. These studies will provide important insight into the physiology of VIP receptor regulation and function to this ubiquitous hormone. This will lead to enhanced understanding mechanisms for VIP-responsive malignancies. Candidate: Dr. Lin Pei, M.D., Ph.D., has a strong background training in molecular biology. During early postdoctoral training at UCLA, she also acquired skills in protein chemistry. This will enable her to effectively perform and interpret the experiments in this proposal. Dr. Pei is committed to applying molecular biological techniques to answer questions of disease pathophysiology and is embarked on a career in academic medicine. She is assured of Departmental support as an independent faculty member both during and by the end of the award. Environment: The applicant will perform the research in the well-equipped laboratory of the sponsor which is funded as a NIDDK Program Project in endocrine aspects of neoplasia. As such, Dr. Pei's proposal will meet with the overall goals of the group. She will have full access to all core facilities available in the Davis Research Building including molecular oligonucleotide synthesis, transgenic mouse and vivarium. There are weekly research-in-progress laboratory meeting, departmental research seminars and visiting scientists (growth factors, transcription, gene regulator) providing continued exposure to basic and clinical research advances. In addition, Dr. Pei will enjoy the continued exposure to the expert endocrine faculty at Cedars-Sinai, as well as associated productive groups in molecular genetics, membrane biology, transplantation biology, virology and protein chemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK002346-01A1
Application #
2134265
Study Section
Special Emphasis Panel (SRC)
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1995-09-30
Budget End
1996-08-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Pei, L (2001) Transcriptional repressor of vasoactive intestinal peptide receptor mediates repression through interactions with TFIIB and TFIIEbeta. Biochem J 360:633-8
Pei, L (2001) Identification of c-myc as a down-stream target for pituitary tumor-transforming gene. J Biol Chem 276:8484-91
Chien, W; Pei, L (2000) A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product. J Biol Chem 275:19422-7
Pei, L (2000) Phosphorylation modulates the function of the vasoactive intestinal polypeptide receptor transcriptional repressor protein. J Biol Chem 275:1176-82
Pei, L (2000) Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. J Biol Chem 275:31191-8
Pei, L (1999) Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells. J Biol Chem 274:3151-8
Pei, L (1998) Molecular cloning of a novel transcriptional repressor protein of the rat type 1 vasoactive intestinal peptide receptor gene. J Biol Chem 273:19902-8
Pei, L (1998) Genomic organization and identification of an enhancer element containing binding sites for multiple proteins in rat pituitary tumor-transforming gene. J Biol Chem 273:5219-25
Pei, L; Melmed, S (1997) Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol 11:433-41
Pei, L (1996) Identification of a negative glucocorticoid response element in the rat type 1 vasoactive intestinal polypeptide receptor gene. J Biol Chem 271:20879-84