Jean Vance
Jean Vance
Ph.D, University of Pittsburgh
FRSC
Professor, Department of Medicine
Research:
Dr. Vance's research focuses on understanding the mechanisms of intracellular lipid trafficking in mammalian cells. She identified a region of the endoplasmic reticulum, designated mitochondria-associated membranes (MAM), which forms contact sites with mitochondrial outer membranes. These contact zones are required for the regulation of calcium homeostasis as well as the import of phosphatidylserine (PS) into mitochondria for decarboxylation to phosphatidylethanolamine (PE) via PS decarboxylase (PSD). Her lab has generated and characterized mice lacking either of the two PS synthases, and mice lacking PSD in which mitochondrial function was severely impaired. Moreover, reduction of PSD expression in cultured cells reduced mitochondrial PE content and markedly reduced mitochondrial functions, demonstrating the importance of a threshold level of PE in mitochondria for normal mitochondrial function. In addition Dr. Vance was a major contributor to a study in which mutations in PS synthase-1 were shown to cause Lenz-Majewski syndrome, a severe developmental disorder. In fibroblasts from these patients, mutations in PS synthase-1 induced a gain-of-function phenotype due to profound attenuation of end-product inhibition of PS synthesis.
Dr. Vance's other major research interest is in cholesterol trafficking in the brain. Her lab has studied cholesterol transport defects in the neurodegenerative disease, Niemann-Pick type C (NPC) disease, using primary neurons and glial cells isolated from brains of NPC1-deficient mice. Her lab recently elucidated neuronal mechanisms in the brain that underlie the beneficial effects of cyclodextrin, currently being investigated as a treatment for NPC disease.
Dr. Vance has served on editorial boards of the Journal of Biological Chemistry and the Biochemical Journal, and is currently an editorial board member of the Journal of Lipid Research and Biochimica Biophysica Acta (Lipids). Dr. Vance was Chair of a Gordon Conference on the Molecular and Cellular Biology of Lipids, as well as Chair of the Deuel Conference on Lipids and of the Kern Aspen Lipid Conference. In addition, she served as co-chair of two international ASBMB conferences on lipids. She co-edited with Dr. Dennis Vance five editions of an advanced textbook: "Biochemistry of Lipids, Lipoproteins and Membranes". Her research contributions were recognized by her election as a Fellow of the Royal Society of Canada.Selected Publications:
- Vance, J.E. (1990) "Phospholipid Synthesis in a Membrane Fraction Associated with Mitochondria". J. Biol. Chem.265, 7248-7256.
- Steenbergen, R., Nanowski, T.S., Beigneux, A., Kulinski, A., Young, S.G. and Vance, J.E. (2005) "Disruption of the Phosphatidylserine Decarboxylase Gene in Mice Causes Embryonic Lethality and Mitochondrial Defects" J. Biol. Chem. 280, 40032-40040.
- Arikketh, D., Nelson, R. and Vance, J.E. (2008) "Defining the Importance of Phosphatidylserine Synthase-1 (PSS1): Unexpected Viability of PSS1-deficient Mice" J. Biol. Chem 283, 12888-12897.
- Peake, K.B. and Vance, J.E. (2012) "Normalization of Cholesterol Homeostasis by 2-Hydroxy-ß-Cyclodextrin in Neurons and Glia from Niemann-Pick C-deficient Mice" J. Biol. Chem. 287, 9290-9298.
- Tasseva, G., Bai, H.D., Davidescu M., Haromy, A., Michelakis, E. and Vance, J.E. (2013) "Phosphatidylethanolamine Deficiency in Mammalian Mitochondria Impairs Oxidative Phosphorylation and Alters Mitochondrial Morphology" J. Biol. Chem. 288, 4158-4173.
- Sousa, S.B., Jenkins, D., Chanudet, E., Tasseva, G., Ishida, M., Anderson, G., Satnier, P., Ryten, M., Sa, J., Saraiva, J.M., Barnicoat, A., Scott, R., Calder, A., Wattanasirichaigoon, D., Chrzanowska, K., Simandlova, M., van Maldergem, L., Beales, P.L., Vance, J.E. and Moore, G.E. (2014) "Gain-of-Function Mutations in the Phosphatidylserine Synthase 1 (PTDSS1) Gene Cause Lenz-Majewski Syndrome" Nature Genetics 46, 70-76.
- Keckesova, Z., Donaher, J.L., De Cock, J., Freinkman, E., Lingrell, S., Bachovchin, D.A., Bierie, B., Tischler, V., Noske, A., Reinhardt, F., Thiru, P., Golub, T.R., Vance, J.E. and Weinberg, R.A. (2016) "LACTB, a tumor suppressor that modulates mitochondrial lipid metabolism and cancer cell differentiation". Nature (in press).