Richard B. Weinberg
Professor of Internal Medicine
Associate in Biochemistry
Associate Director, General Clinical Research Center 
 

A.B., 1971 Harvard University 
M.D., 1975 Johns Hopkins University

Email: weinberg@wfubmc.edu 
Phone: 336-716-4638

Research in our laboratory is focused upon the elucidation of the structure and function of human apolipoprotein A-IV (apo A-IV), a 46 kD intestinal protein that is synthesized during lipid absorption and incorporated into the surface of nascent chylomicrons. Recently, we have found that apo A-IV possesses dynamic interfacial properties that are optimal for stabilizing surface tension and molecular packing at lipid/aqueous interfaces. We propose that by controlling the density of lipid packing at the expanding chylomicron surface, apo A-IV can modulate the efficiency of intestinal lipid absorption.

We utilize a broad array of biophysical techniques to study the structure-function relationships of apo A-IV. We use UV, fluorescence, and circular dichroism spectroscopy to probe the effect of naturally occurring and recombinant apo A-IV mutations on its molecular structure. We then use sophisticated surface chemistry techniques, such as a Langmuir surface balance and an ITC oil-drop tensiometer to examine how structure alterations in apo A-IV affect its interfacial behavior and ability to stabilize expanding lipid surfaces.

A second aim of our research examines the functional genomics of apo A-IV. We use human apo A-IV transgenic and knock-out mice to examine the impact of apo A-IV expression and dietary fatty acids on intestinal cholesterol absorption. We also study the interaction of diet and human genetic apo A-IV polymorphisms of cholesterol absorption and triglyceride metabolism in the General Clinical Research Center.

We expect that these studies will provide novel insights into the specific biological function of apo A-IV, the complex process of cholesterol absorption, and the impact of apo A-IV genetic polymorphisms on the dietary treatment of atherosclerotic cardiovascular disease. This research has been continuously supported by the NIH National Heart, Lung, and Blood Institute for over 16 years; our current funding cycle extends through 2004. Opportunities exist for both pre- and post-doctoral study. 

Recent Publications (selected):

Hockey KJ, Anderson RA, Hantgan RR, Weinberg RB: Effect of the apolipoprotein A-IV Q360H polymorphism on post-prandial plasma triglyceride clearance. J Lipid Res 42:211-217 (2001).

Weinberg RB, Geissinger BW, Kasala K, Hockey KJ, Terry JG, Easter L, Crouse JR: The effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption. J Lipid Res 41:2035-2041 (2000).

Weinberg RB, Anderson RA, Cook VR, Emmanuel F, Denefle P, Hermann M, Steinmetz A: Structure and interfacial properties of chicken apolipoprotein A-IV. J Lipid Res (cover article) 41:1410-1418 (2000).

Weinberg RB, Cook VR, Delozier JA, Shelness GS: Dynamic interfacial properties of human apolipoproteins A-IV and B17 at the air/water and oil/water interface. J Lipid Res 41:1419-1427 (2000).

Weinberg RB: The apolipoprotein A-IV-2 allele: association of its worldwide distribution with adult persistence of lactase and speculation on its function and origin. Genet. Epidemiol. 17:285-297 (1999).