Ronald P. Lynch Dean of the College of Agriculture and Life Sciences
Professor of Molecular Biology and Genetics
Publications | Research | Faculty
Background:
Susan Henry is the Ronald P. Lynch Dean of the College of Agriculture and Life Sciences, and Professor of Molecular Biology and Genetics. Dr. Henry received her B.S. degree in Zoology from the University of Maryland and her Ph.D. degree in Genetics from the University of California at Berkeley. She is a Fellow of the American Association for the Advancement of Science, and a Fellow of the American Academy of Microbiology. Dr. Henry's research is supported by a grant from the NIH.
Research Focus:
The research in Susan Henry’s laboratory focuses on regulation of membrane lipid metabolism in yeast and its coordination with membrane trafficking and signal transduction (Jesch et al., 2006; Gaspar et al., 2006; Gaspar et al., 2008; Nunez et al., 2008). We have shown that signals arising from lipid metabolism in the endoplasmic reticulum (ER) influence major transcriptional networks in the cell (Gaspar et al., 2006a; Jesch et al., 2006; Jesch et al., 2005; Loewen et al., 2004). This metabolism influences, and is influenced by, several major signal transduction pathways including the unfolded protein response pathway (Chang et al., 2004; Chang et al., 2002) and the protein-kinase (PKC) pathway (Sreenivas et al., 2001 Nunez et al., 2008;) and the glucose response pathway (Shirra et al., 2001).
Our work has focused on the relationship of transcriptional and metabolic responses to the phospholipid precursor, inositol. The transcription patterns of over 700 genes are altered within two hours (equivalent to about one doubling time) following introduction of inositol. Statistical analysis identified at least six distinct expression responses (Jesch et al., 2006) including repression of phospholipid biosynthetic genes regulated by Opi1p, as well as genes regulated by the UPR pathway and transient induction of lipid remodeling genes regulated by Mga2p. These three categories of genes are known to respond to signals arising in the ER and the kinetics of the changes in their transcript abundance were rapid, occurring within the first 15 to 30 minutes following introduction of inositol. Analysis of changes in lipid metabolism over the same time frame revealed rapid consumption of phosphatidic acid (PA) which was shown to interact with Opi1p and to be required for its retention in the ER (Loewen et al., 2004). Consumption of PA results in translocation of Opi1p to the nucleus and repression of phospholipid biosynthetic genes including INO1.
Cells defective in Protein Kinase C (PKC) signaling proved to be unable to adapt to growth in the absence of inositol. Wild type cells shifted to inositol-free medium activated PKC signaling via the Mpk1p protein kinase and the Rlm1p transcription factor, upregulating a number of Rlm1p target genes. Cells defective in PKC signaling were unable to mount this transcription response to inositol deficiency and also exhibited major changes in lipid metabolism (Nunez et al., 2008).
Cells defective in endoplasmic reticulum (ER) to Golgi trafficking such as the temperature sensitive sec13-1 mutant were shown to exhibit major changes in lipid metabolism upon shift to their restrictive temperature. Specifically, these cells exhibited a rapid decrease in synthesis of phosphatidylinositol (PI), while PI synthesis in wild type cells increased at higher temperatures. Simultaneously, sec13-1 cells increased synthesis of triacylglycerols (TAG) and other neutral lipids and accumulated lipid droplets upon shift to the restrictive temperature. Sec13-1 cells in which structural genes for the major TAG synthases were deleted exhibited decreases in their restrictive temperatures, indicating that synthesis of TAG under conditions in which ER to Golgi trafficking is impaired is physiologically relevant (Gaspar et al., 2008).
Links
Click here to view Dr. Henry's PubMed listings.
PUBLICATIONS 2004-PRESENT
C.J.R. Loewen, M. L. Gaspar, S. A. Jesch, C. Delon, N. T. Ktistakis, S. A. Henry, and T. P. Levine. 2004. Phospholipid Metabolism Regulated by a Transcription Factor Sensing Phosphatidic Acid. Science, 304: 1644-1647.
H. J. Chang, S. A. Jesch, M. L. Gaspar, and S. A. Henry. 2004. Role of the Unfolded Protein Response Pathway in Secretory Stress and Regulation of INO1 Expression in Saccharomyces cerevisiae. Genetics, 168: 1899-1913.
S. A. Jesch, X. Zhao, M. T. Wells, and S. A. Henry. 2005. Genome Wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast. J. Biol. Chem., 280: 9106-9118.
L. R. Nunez and S. A. Henry. 2005. Regulation of 1D-myo-inositol-3-phosphate Synthase in Yeast. In: Subcellular Biochemistry: Biology of Inositols and Phosphoinositides, Ed. A. L. Majumder and B. B. Biswas, Kluwer Academic/Plenum Publishers, London, UK, Vol. 39: 135-156.
S. A. Jesch and S. A. Henry. 2005. Yeast Inositol Lipids: Synthesis, Regulation, and Involvement in Membrane Trafficking and Lipid Signaling. In: Cell Biology and Dynamics of Yeast Lipids, G. Daum (Ed.). Research Signpost, Kerala, India, Vol: 37/661: 105-131.
H. A. Boumann, J. Gubbens, M. C. Koorengevel, C. S. Oh, C. E. Martin, A. J. Heck, J. Patton-Vogt, S. A. Henry, B. de Kruijff, and A. I. de Kroon. 2006. Depletion of Phosphatidylcholine in Yeast Induces Shortening and Increased Saturation of the Lipid Acyl Chains: Evidence for Regulation of Intrinsic Membrane Curvature in a Eukaryote. Mol Biol Cell, 17:1006-1017.
M. L. Gaspar, M. A. Aregullin, S. A. Jesch, and S. A. Henry. 2006a. Inositol Induces a Profound Alteration in the Pattern and Rate of Synthesis and Turnover of Membrane Lipids in Saccharomyces cerevisiae. J. Biol. Chem., 281: 22773-22785.
S. A. Jesch, P. Liu, X. Zhao, M. T. Wells, and S. A. Henry. 2006. Multiple endoplasmic reticulum-to-nucleus signaling pathways coordinate phospholipid metabolism with gene expression by distinct mechanisms. J. Biol. Chem., 281: 24070-24083.
M. L. Gaspar, M. A. Aregullin, S. A. Jesch, L. R. Nunez, M. Villa-Garcia, and S. A. Henry. 2006b. The emergence of yeast lipidomics. In: Regulation of Lipid Metabolism in Yeast, G. Carman and S. A. Henry (Ed.). Biochimica et Biophysica Acta, in press.
Nunez, L. 2006. Phospholipid biosynthesis in yeast: The role of the PKC1-MPK1 signal transduction pathway, Ph.D. Thesis, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY.
E. L. Krause, M. J. Villa-Garcia, S. A. Henry, and L. P. Walker. 2007. Determining the effects of inositol supplementation and the opi1 mutation on ethanol tolerance of Saccharomyces cerevisiae. Industrial Biotech., 3: 260-268.
G. M. Carman and S. A. Henry. 2007. Phosphatidic acid plays a central role in the transcriptional regulation of glycerophospholipid synthesis in Saccharomyces cerevisiae. J. Biol. Chem., 282: 37293-37297.
M. L. Gaspar, S. A. Jesch, R. Viswanatha, A. L. Antosh, W. J. Brown, S. D. Kohlwein, and S. A. Henry. 2008. A block in endoplasmic reticulum-to-Golgi trafficking inhibits phospholipid synthesis and induces neutral lipid accumulation. J. Biol. Chem., 283: 25735-25751.
L. R. Nunez, S. A. Jesch, M. L. Gaspar, C. Almaguer, M. Villa-Garcia, M. Ruiz-Noriega, J. Patton-Vogt and S. A. Henry. 2008. Cell wall integrity MAPK pathway is essential for lipid homeostasis. J. Biol. Chem., 283: 34204-24217.