jzw1@columbia.edu

ASSOCIATE PROFESSOR OF MEDICINE AND PHARMACOLOGY

Sterol mediated control of transcription; molecular analysis of ion channels

We are studying the molecular biology of two cell surface proteins that are important to both normal and abnormal function of the cardiovascular system. We seek to understand the molecular mechanisms controlling expression of the low density lipoprotein (LDL) receptor. This receptor is important in maintaining intracellular and whole organism cholesterol homeostasis. Normally cholesterol circulates in the blood primarily in the form of LDL particles. These particles are endocytodes, and cholesterol is liberated. As cytoplasmic levels of cholesterol and its derivatives rise, transcription of the LDL receptor gene is repressed. We are in the process of isolating nuclear proteins that bind to specific control regions in the promoter of this gene which are involved in the process of feedback repression of transcription. Another approach to understanding this mechanism involves a search for mutant cell lines with a defect in this process. Our goal is to understand both the intracellular signaling pathways and transcriptional control mechanisms involved in control of this receptor.

Another complex of cell surface proteins which are important in control of cardiac function, as well as muscle and nervous system function, are the voltage-gated calcium channels. These channels, together with other ionic channels, control electric signal generation and transmission in these tissues. Although similar channels are found in various tissues, distinct electrical activities of the corresponding Ca⁺⁺ channels suggest the likelihood that distinct channels are being expressed. Using probes derived from an already available skeletal muscle Ca⁺⁺ channel cDNA sequence, we are probing cDNA libraries to find the cardiac homologues of the muscle channel. Our goals in these studies are to understand the molecular basis of the heterogeneity of ionic channel function, and to provide structural insight into the function of these channels.

Selected Publications:

1. Reed EF, Hong B, Ho E, Harris PE, Weinberger J and Suciu-Foca N: Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation 61:566-572, 1996. Abstract

2. Gu J-W, Santiago D, Olowe Y and Weinberger J: Basic fibroblast growth factor as a biochemical marker of exercise-induced ischemia. Circulation 95:1165-1168, 1997. Abstract Full Text

3. Amols HI, Trichter F and Weinberger J: Intracoronary radiation for prevention of restenosis: Dose perturbations caused by stents. Circulation 98:2024-2029, 1998. Abstract PDF File

4. Weinberger J, Giedd KN, Simon AD, Marboe C, Knapp FF, Trichter F and Amols H: Radioactive beta-emitting solution-filled balloon treatment prevents porcine coronary restenosis. Cardiovasc. Rad. Med. 1:252-256, 1999. Abstract

5. Qu X and Weinberger J: Novel b-emitting poly(ethylene terephthalate) surface modification. J. Biomed. Mater. Res. 52:492-497, 2000. Abstract PDF File