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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
Lily Y. Jan, Ph.D.
Professor of Physiology and Biochemistry & Biophysics; Investigator, Howard Hughes Medical Institute; Jack and DeLoris Lange Endowed Chair of Physiology and Biophysics
Research Interests:
Studies of potassium channels
Summary:
Potassium channels are widely distributed. In the brain, potassium channels regulate neuronal signaling. Potassium channels may also regulate cell volume and the flow of salt across epithelia, control heart rate, vascular tone, the release of hormones such as insulin, and protect neurons and muscles under metabolic stress.
How can potassium channels serve so many different physiological functions? Potassium channels come in many different flavors; they differ in how their activities are regulated as well as the exact manner they allow passage of potassium ions. Many different potassium channels often co-exist in a cell. This richness in potassium channel variety was one of the factors that stemmed early attempts for biochemical purification of potassium channels.
How does a potassium channel allow potassium ions but not the smaller sodium ions to go through? How does a potassium channel alter its activity in response to electrical and chemical signals? How do potassium channels contribute to signaling and plasticity in the brain? How does a cell control the number and type of potassium channels in its subcellular compartments? How might potassium channels have arisen during evolution? We have been fascinated with these questions, and believe what potassium channels will teach us may also be of relevance to other membrane proteins.
To study potassium channels, we have chosen a molecular approach that isolates individual potassium channel genes so that the channels they give rise to can be studied one at a time and then compared with potassium channels in native tissues. This molecular study was initiated by positional cloning of the Shaker voltage-gated potassium (Kv) channel gene in the fruit fly and expression cloning of mammalian inwardly rectifying potassium (Kir) channels, founding members of two large, distantly related families of potassium channels in organisms ranging from bacteria to man.
Potassium channel mutations cause diseases of the brain (epilepsy, episodic ataxia), ear (deafness), heart (arrhythmia), muscle (myokymia, periodic paralysis), kidney (hypertension), pancreas (hyperinsulinemic hypoglycemia, neonatal diabetes), and developmental abnormalities of neural crest-derived tissues (Andersen's syndrome). Conversely, the KCNK9 potassium channel gene acts as a dominant oncogene and is amplified or otherwise over-expressed in several types of human carcinomas. Underscoring potassium channels' critical physiological functions, potassium channel openers and blockers have been developed for pharmaceutical purposes. A better understanding of potassium channel function will not only satisfy our curiosity, but will have clinical significance.
How do we study potassium channels? One unique advantage in channel studies is the possibility to examine one channel at a time, with sub-millisecond resolution, for many seconds, in experimentally determined intracellular and extracellular environments. In addition to biophysical, biochemical, and cell biological studies of channel assembly, trafficking, regulation and function, we need to learn how potassium channels are targeted to specific subcellular compartments of neurons in the mammalian brain, how they respond dynamically to neuronal activity and in turn modulate neuronal signaling. To understand how potassium channels work, it will be necessary to explore advances in genomics as well as genetics, and incorporate any useful methodologies suited for membrane proteins.
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