Faculty



Lois S. Weisman

Sarah Winans Newman Collegiate Professor in the Life Sciences, Research Professor, Life Sciences Institute and Professor of Cell and Developmental Biology, Medical School

Ph.D., University of California, Berkeley
Postdoctoral Fellow, UCLA

Research Focus: Myosin V based transport, and phosphoinositide lipid signaling in yeast and in neurons

Phone: 734.647.2539
E-mail: lweisman@umich.edu


How studies of yeast and protein biochemistry aid in understanding human diseases

Our laboratory studies how the yeast lysosome (vacuole) is partitioned between mother and daughter cells during cell division. Yeast have been instrumental in determining the molecular basis of many biological processes in higher eukaryotes. These include events that are unique to complex, multi-cellular organisms. For example several advances in understanding the molecular basis of synaptic transmission came from studies in yeast. Our studies of vacuole inheritance are likely to provide general insight into organelle movement, cell polarization/differentiation and cellular signaling. Unexpectedly, they have also revealed new information about synaptic transmission. Vacuole inheritance is a highly dynamic, regulated process. In order to identify the molecules required, we developed screens for yeast vac mutants. Analysis of these mutants led to the discovery that there are organelle-specific, myosin V transport complexes. The complex for the vacuole is very similar to a complex that moves melanosomes in melanocytes, and synaptic vesicles in neurons. We have recently found that the regulated synthesis and turnover of this complex deposits the vacuole at the correct place at the proper time. We have also discovered a set of mutants that are defective in the phosphatidylinositol 3,5 bis-phosphate lipid signaling pathway. Molecules required for this pathway include Fab1, Vac7, Vac14 and Fig4. While these proteins were first identified in yeast, higher eukaryotes also have genes encoding Fab1/PIKfyve, Vac14 and Fig4. Minor changes in this pathway cause severe neurological diseases, including Charcot-Marie-Tooth syndrome and ALS. In addition, mutations that partially affect this pathway in mice lead to neurodegeneration and perinatal lethality. Based on these observations we are focused on the following questions. 1) How is the PI3,5P2 lipid signaling pathway regulated? 2) What are the downstream effectors that are regulated by this lipid? 3) Are defects in this pathway a common cause of human disease? 4) Does upregulation of this pathway show therapeutic value? If we find that it does, then we will pursue a screen that we developed for drugs that can modulate this pathway. The above studies are being pursued using isolated recombinant proteins, analysis of yeast mutants, cultured mammalian cells and mice.

 

Weisman Research Group

 

Awards

2013 Induction into the Douglass Society, highest honor conferred on alumnae of Douglass College, Rutgers University
2012 Elected, Fellow, American Association for the Advancement of Science
2009-2019
NIH NIGMS MERIT Award
2007
NIH Pioneer Award Finalist
2005-present
Sarah Winans Newman Collegiate Professor in the Life Sciences
2001-2004
American Heart Established Investigator Award


Representative Publications

  1. Jin, Y. and Weisman, L.S. (2015) The vacuole/lysosome is required for cell-cycle progression. eLife, DOI: http://dx.doi.org/10.7554/eLife.08160. PMCID: PMC4586482.

  2. McCartney, A.J., Zolov, S.N., Kauffman, E.J., Strunk, B.S., Zhang, Y., Weisman, L.S. and Sutton, M. (2014) Activity-dependent PI(3,5)P2 synthesis controls AMPA receptor trafficking during synaptic depression. PNAS, 111:E4896-48905. PMCID: PMC4234577.

  3. Jin, N., Mao, K., Jin, Y., Tevzade, G., Kauffman, E.J., Park, S., Bridges, D., Loewith, R., Saltiel, A.R., Klionsky, D.J. and Weisman, L.S. (2014) Roles for PI(3,5)P2 in nutrient sensing through TORC1. Mol. Bio. Cell, 25:1171-1185. PMCID: PMC3967979.

  4. Yau, R.G.W., Peng, Y., Valiathan, R., Birkeland, S.R., Wilson, T.E. and Weisman, L.S. (2014) Release from myosin V via spatially regulated recruitment of an E3 Ub ligase controls organelle localization. Dev. Cell, 28:520-533. PMCID: PMC3994899.

  5. Zolov S.N., Bridges, D., Zhang Y., Lee, W-W., Riehle, E., Verma R., Lenk, G.M., Converso-Baran, K., Weide, T., Albin R.L., Saltiel, A.R., Meisler, M.H., Russell, M.W. and Weisman L.S. (2012) In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. PNAS, 109:17472-7. PMCID: PMC3491506.

 

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