Ashrafi, Kaveh
Barber, Diane L
Bernstein, Harold S.
Black, Brian L
Blanc, Paul D
Boushey, Homer A
Broaddus, V Courtney
Brown, James K
Caughey, George H
Chapman, Harold A
Charo, Israel F
Chatterjee, Kanu
Chuang, Pao-Tien
Clyman, Ronald I
Conklin, Bruce R
Coughlin, Shaun R
Derynck, Rik M
Dobbs, Leland G
Eisner, Mark D
Engel, Joanne N
Erle, David J
Fahy, John Vincent
Farese, Robert V
Fielding, Christopher J
Fielding, Phoebe
Fineman, Jeffrey R
Glantz, Stanton A
Grossman, William
Hawgood, Samuel
Ingraham, Holly A
Jan, Lily Y
Kan, Yuet W
Kane, John P
Kornberg, Thomas B
Kurtz, Theodore W
Kwok, Pui-Yan
Lazarus, Stephen C
Malloy, Mary J.
Martin, Gail R
Matthay, Michael A
Mcdonald, Donald M
Mikawa, Takashi
Minor, Daniel L
Mostov, Keith E
Nadel, Jay A
Ordahl, Charles P
Pitas, Robert E
Reiter, Jeremy F.
Rosen, Steven D
Shaw, Robin M.
Sheppard, Dean
Simpson, Paul C
Stainier, Didier Y. R.
Wang, Rong
Weiner, Orion D
Weisgraber, Karl H
Weiss, Arthur
Weiss, Ethan J
Werb, Zena
Wiener-Kronish, Jeanine
Young, William L

CVRI Scientists

John P. Kane, M.S., M.D., Ph.D.
Professor of Medicine and Biochemistry & Biophysics

Research Interests:
Structure and function of lipoproteins; genetic determinants of arteriosclerosis

Summary:
Because it has been found that faulty transport of cholesterol and other lipids is an underlying element in the development of arteriosclerosis, elucidation of molecular mechanisms involved in cholesterol transport has been a major goal of this group. This has led to the identification of previously unidentified proteins that participate in the process. Certain complexes of cholesterol and other fatty substances with proteins (lipoproteins) are known to convey cholesterol to the artery wall to initiate the formation of diseased areas (plaques) that can eventually lead to occlusion of arteries serving the heart or brain. Others (High Density Lipoproteins, HDL) have the task of removing cholesterol to protect the arteries. Understanding how HDL accomplish this task requires the discovery and characterization of previously unknown molecular complexes. Whereas it was thought that there were two species of HDL, work by this group has identified sixteen to date, detecting the different proteins that comprise each species using the technique of mass spectrometry. Studies are conducted in parallel to discover the biochemical pathways by which they are assembled, and the processes they mediate. This has led to the discovery of species that have antioxidant and anti-inflammatory activities, and another that protects humans against the organism that causes Trypanosomiasis, better known as African sleeping sickness. It has also been found that the removal of chemically injurious fatty substances from the retina involves HDL, leading to important new insights that can be applied to understanding macular degeneration, the leading cause of blindness in people over fifty years of age in the U.S.

Another goal in this laboratory is the discovery of genes related to the development of heart attacks and stroke. To accomplish this, a very large collection of human DNA, approaching 30,000 individual samples, has been assembled by the group. Each sample is accompanied by an extensive clinical history. Over twelve thousand genes have been studied thus far. Variations in twenty-one genes have now been found to be associated with heart attack and four genes have been linked to stroke. Because risk genes may interact with one another, the group is collaborating with the Los Alamos National Laboratory, using its supercomputers to develop new mathematical formulas for accomplishing this challenging task. Discovery of the genes that are linked to heart attack and stroke is expected to lead to new strategies for prevention and treatment of those diseases. Other targets of the genetic research by this group that are related to heart disease are diabetes, HDL deficiency states, other lipoprotein disorders, and macular degeneration. Six previously unrecognized diseases caused by defective genes have been discovered in this effort.

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