University of California, San Francisco
Dr. Jan is also Jack and DeLoris Lange Professor of Physiology and Biophysics at the University of California, San Francisco.
Lily Jan's lab started their ion channel studies with molecular identification of the founding members of voltage-gated potassium channels (1987) and inwardly rectifying potassium channels (1993) and identification of TMEM16A and TMEM16B as calcium-activated chloride channels (2008). They now ask how these ion channels work, how the channel activity may be regulated at the level of channel property as well as channel density and localization, and how these channels contribute to cellular functions such as neuronal signaling.
Potassium channels serve as the gatekeepers of the cell membrane, admitting millions of potassium ions each second while intercepting all but one smaller sodium ion for every 1,000 potassium ions. It is this calculated flow of ions through the cell membrane that sends electrical impulses from the brain to specific destinations in the body, controlling functions such as the rate of the heartbeat and the movement of muscles. Potassium channel activities in other organs control the release of insulin and the flow of blood. In recent years, scientists have linked malfunctions of potassium channels to epilepsy, heart arrhythmias, deafness, and other diseases.
Neurobiologist Lily Y. Jan studies how potassium channels regulate the signaling of neurons in the brain. Specifically, she hopes to answer questions that have long intrigued scientists. Among them: How does a potassium channel allow potassium ions to enter the cell but not the smaller sodium ions? 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?
Jan works alongside her husband, fellow HHMI investigator Yuh Nung Jan, whose research focuses on the development of the nervous system. The two married in 1971, when they were graduate students at the California Institute of Technology, and have shared a laboratory since 1979. In 1987, they were the first to determine the DNA sequence of a potassium channel—the Shaker channel in fruit flies. This discovery laid the groundwork for studies by the Jans and others showing that potassium channel mutations in fruit flies cause the same health problems as similar mutations in higher organisms, including humans.
Despite her accomplishments in the field of neurobiology, Lily's early research interests were in physics. After earning a bachelor's degree in physics, she began her Ph.D. studies at Caltech set on a career in theoretical high-energy physics. During her second year of studies, however, one of her professors, the late Max Delbrück, a winner of the 1969 Nobel Prize in Physiology or Medicine, invited a colleague from UC Berkeley to give a weekly physics seminar, hoping that it would encourage physics students to become more aware of and interested in modern biology. It was a lecture that literally changed her career.
Delbrück, himself a physicist turned biologist, provided the guidance Jan needed to make the career switch to neurobiology. "I learned so much from Max Delbrück," Jan explained. "In his biophysics journal club, we covered any and all emerging topics that struck Max's interest; in his laboratory, casual and sincere discussions were initiated naturally when he strode by; and in his home, Max and his wife Manny graciously hosted students and celebrated their milestones with skits and puppet shows. Instead of getting one important lesson, I saw Max demonstrate his way of doing science and nurturing others in the scientific community."
Later, when Lily and Yuh Nung, who also had switched the focus of his studies from physics to biology, had to choose lab partners in a neurobiology course, they chose each other. The rest is history, so they say. In marriage and in the laboratory, they have worked as a team. When their two children were young, they took turns caring for them and working in shifts in the laboratory. "This made sense professionally as well, giving us the opportunity to achieve more together than we could manage individually," Jan said.
The Jans' recent research interests in neuronal function and development converge on the neuron's dendrites. Among the questions to be addressed are these: How do neurons elaborate their distinctive dendritic trees? How might neuronal activities alter the ways neurons process signals impinging onto their dendrites?