by Connie Jeffery and Gabriela Popescu
Lily Jan is the Jack and DeLoris Lange Professor of Molecular Physiology at the University of California at San Francisco (UCSF) and the Howard Hughes Medical Institute (HHMI).
Born in Fu-chow, China, she moved with her family to Taiwan as a baby. After majoring in physics as an undergraduate at the National Taiwan University, Lily moved to Caltech in 1968 to continue studying theoretical high-energy physics, but switched to biology after attending a seminar sponsored by Max Delbruck, winner of the 1969 Nobel Prize in Physiology or Medicine. She moved to his lab to complete her Ph.D. thesis research and learned a lot through the guidance of Delbruck, a fellow physicist-turned-biologist. Around that time she also started collaborating with Yuh Nung, her husband, and they continue as a team to this day. A summer lab course at Cold Spring Harbor Laboratory helped her get started learning neurobiology in preparation for her postdoc and also led to long term friendships and collaborations. She continued at Caltech for postdoctoral research with Seymour Benzer and then moved to Harvard Medical School to work with Steve Kuffler where she showed that some peptides function as neurotransmitters.
Lily and Yuh Nung started as assistant professors at UCSF in 1979 and were chosen to be HHMI investigators in 1984. Their research led to a major achievement in our understanding of ion channels in 1987: the cloning of the founding members of the voltage-gated potassium channel family, shaker and its mammalian homolog. The flow of potassium ions through these transmembrane channels is a key part of neuronal signaling from the brain throughout the body. Potassium channel activity is needed for everything from muscle contraction to maintaining the heart rate. Problems in function of potassium channels are linked to many diseases including heart arrhythmias, deafness, high blood pressure, neonatal diabetes, and epilepsy.
Another important factor about this achievement was that identifying the sequence of shaker and its human homolog helped show that mutations in fruit flies can lead to physical problems similar to those brought about by comparable mutations in humans. The lab continued to make important discoveries as they also cloned the first members of the inwardly rectifying potassium channel and a calcium-activated chloride channel protein families. Related projects in neural development led to discoveries of proteins involved in the molecular mechanisms by which neurons acquire their specific cell fates and morphologies, including a proneural gene that endows cells with a neuronal cell fate (atonal) and a protein found in neural precursar cells and involved in cell fate determination (numb).
Current questions being addressed in the lab include the mechanisms of ion channel activity and how they are regulated – both through regulation of channel activity in response to electrical and chemical signals as well as how their number and cellular location are regulated. The lab is also interested in how diversity is generated in neuronal morphology, especially in the development of dendritic trees, and how dendritic morphogenesis and channel modulation contribute to the wiring of the nervous system and plasticity of neuronal circuits in the brain.
Lily’s work in biophysics and neuroscience has led to her receiving many awards including the Gruber Foundation Neuroscience Prize, the Wiley Prize in Biomedical Sciences, the Edward M. Scolnick Prize in Neuroscience (McGovern Institute for Brain Research at MIT), and the Ralph W. Gerard Prize (Society for Neuroscience). She has been elected to the National Academy of Sciences, the American Academy of Arts and Sciences, and the Academia Sinica (Taiwan).
In addition to their teamwork in the laboratory, Lily and Yuh also worked as a team in raising their two children. When the children were young, Lily and Yuh took shifts working in the lab and taking care of the children. They took turns going to conferences so that one was always home with the children.
In her autobiography, she concludes with a number of reflections: First, she mentions the importance of working at top research institutions with first-rate peers who help inspire each other: National Taiwan University, Caltech, HMS, UCSF, and HHMI. She notes the importance of nurturing and enhancing the careers of students or postdocs who join the lab, and the value of the freedom to choose research projects, enabled by her financial support from HHMI. And finally, she emphasizes the significance of choosing interesting and important research problems, saying, “It takes just as much effort to study something relatively trivial; you might as well choose some potentially important problems to work on.”