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| 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 |
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CVRI Scientists
Steven D. Rosen, Ph.D.
Professor of Anatomy
Research Interests:
Molecular mechanisms of leukocyte-endothelial interactions
Summary:
There are a number of ' inflammatory diseases' in which white blood cells in the blood migrate into tissues and produce damage. Two of the most serious diseases of this kind are rheumatoid arthritis (RA) and bronchial asthma. The invading white blood cells damage the tissue, for example by degrading cartilage in joints or by producing substances that cause the airways to narrow in asthma. We are studying how white blood cells migrate from the blood into these tissue sites. Under normal circumstances, white blood cells are an essential part of the body's defense against infections and diseases and they patrol blood and return to specialized organs (such as lymph nodes) where an immune response can be initiated. This process occurs in response to chemical signals instructing the white blood cells to enter these organs by exiting through blood vessels that supply the organs.
We have identified novel enzymes that are critical to producing the chemical signals which recruit white blood cells to lymph nodes under normal conditions. Our work indicates that these same enzymes are also involved in attracting white blood cells to the joints or lungs, thereby causing the painful inflammation associated with arthritis or the difficulty in breathing for asthmatics. Interfering with these enzymes or the chemical signals they produce will block the migration of white blood cells to these tissues and thereby prevent the damage that they produce. To study arthritis, we are using a mouse model of RA in which white blood cells invade and damage the joints. Using recombinant DNA technology, we have generated mice lacking the enzymes. Understanding the invasion processes in these mice may help us to explain the analogous processes in RA. With this understanding may come new therapeutic approaches for treatment of this condition. We are also studying asthma in sheep models of this disease looking for interventions that block the chemical signals which attract white blood cells to the lungs. Success here may lead to the development of new drugs to treat asthma, a disease of increasing incidence in the world.
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