Lois Weisman researches the underlying causes of neurodegeneration and other neurological diseases, of which little is known. Her work focuses on myosin V based transport and phosphoinositide lipid signaling in yeast and neurons, with the overall goal of uncovering new, essential subcellular processes and to determine how these impact human physiology.
Currently, Weisman is pursuing research about the PI3,5P2 signaling pathway, which her lab found causes a severe neuropathy in people when there are even minor defects in the pathway. It was an unexpected discovery; now, she is focused on understanding how the pathway is regulated, what downstream effectors are regulated by PI3,5P2, and if defects in the pathway are a common cause of human disease. She hopes to find that upregulation of this pathway will show therapeutic promise.
In addition, Weisman is working on solving a second puzzle: how do organelles move to the correct place at the proper time? This directed organelle movement is critical during cell division and differentiation, and defects in the movement have wide-ranging effects, such as neurological disease and defects in pigmentation.
Prior to joining the faculty at the University of Michigan Life Sciences Institute, Weisman was a Professor of Biochemistry at the University of Iowa. Weisman is currently the Sarah Winans Newman Collegiate Professor in the Life Sciences.
Innovations & Discoveries
Discovered that the yeast vacuole is inherited in a process that is controlled both spatially and temporally
Weisman discovered a means to produce an endogenous fluorophore in yeast vacuoles and documented their fate during cell division. She discovered that vacuole inheritance is tightly controlled both spatially and temporally — demonstrating that vacuole inheritance provides an excellent model to determine fundamental mechanisms of how subcellular pathways are coordinated in space and time.
Discovered mechanisms that enable Myo2 to specifically attach and detach from the vacuole, and mechanisms for how a myosin V motor transports multiple types of cargoes to distinct subcellular locations at different times
It was previously thought that myosin V motors attached to membranes via binding to lipids, and that organellar proteins were not required. The Weisman lab discovered Vac17 and Vac8, and found that they are myosin V cargo adaptors. Moreover, Vac17 is specifically required for movement of the vacuole, but not for the other five known Myo2 cargoes. Thus, Vac17 specifically regulates vacuole movement. Furthermore, Vac17 plays a critical role in the initiation of vacuole movement. With S. Ramaswamy, the lab determined a 2.2 angstrom, high-resolution structure of the cargo binding domain of Myo2. Utilizing genetic analysis, Weisman and her group mapped surface residues required to bind to Vac17 and a distinct region required to bind to secretory vesicles. Moreover, they mapped the binding sites for nine Myo2 adaptors.
Discovered the machinery required for the synthesis and dynamic regulation of the signaling lipid, PI(3,5)P2, and gained insights into its downstream effectors
The Weisman lab, and others, discovered that PI(3,5)P2 synthesis is catalyzed by the lipid kinase Fab1 (named PIKfyve in mammals). PI(3,5)P2, is an exceedingly low abundance and essential signaling lipid, yet little is known about its roles or its dynamic regulation. The lab developed a method to measure PI(3,5)P2, and uncovered a striking feature that specific stimuli in yeast induce a rapid, transient 20-fold elevation of PI(3,5)P2. We also discovered that PIKfyve provides most of the cellular pools of PI5P, and discovered that dynamic regulation of PI(3,5)P2 is critical for synaptic plasticity.
- saccharomyces cerevisiae
- cell cycle
- myosin type V motors
- A.B., Chemistry, Rutgers University
- Ph.D, Biochemistry, University of California-Berkeley
Honors & Awards
- Induction into the Douglass Society, highest honor conferred on alumnae of Douglass College, Rutgers University (2013)
- Elected Fellow, American Association for the Advancement of Science (2012)
- American Heart Established Investigator Award (2001-2004)
- National Science Foundation Early Career Development Award (1996-2000)
Professional Memberships & Other Service
- Editorial Board, Journal of Cell Biology