Dr. Jennifer Watts
Room: BLS 433
Room: BLS 440
Research & Interests
Our lab is interested in the mechanisms through which the physical properties and regulatory actions of specific lipids impact the cell biology and physiology of animals. The implications of this research extend from understanding how specific fatty acids affect cell signaling to dissecting the fat regulatory pathways involved in obesity and related diseases. We use the nematode modelCaenorhabditis elegans and a combination of genetic, genomic and biochemical approaches to understand the regulation, function and biosynthesis of unsaturated fatty acids.
Genetic pathways of fat storage
Animals deficient in stearoyl-CoA desaturase have reduced fat content. We are currently using C. elegans mutants to examine how fatty acid desaturase pathways interact with other metabolic pathways that regulate fat storage. We have identified transcriptional regulators of stearoyl-CoA desaturase, including several nuclear hormone receptors and SREBP (sterol repeat element binding protein). These important regulators of lipid homeostasis are involved in the end-product feed-back regulation of transcription of lipid metabolism genes in mammals. Studies of these proteins in C. elegans contribute to the understanding, and possibly the future manipulation, of fat regulatory pathways involved in obesity and related diseases.
Functions of polyunsaturated fatty acids
Unsaturated fatty acids play vital roles as structural components of membranes and as signaling molecules. We have isolated C. elegans mutants with altered capacity to synthesis unsaturated fatty acids. These mutants provide new tools to understand the roles unsaturated fatty acids in membrane biology and cell function. We discovered that dietary supplementation with an omega-6 long-chain polyunsaturated fatty acid, DGLA (20:3n-6), causes defects in the development and maintenance of germ cells. Nematodes feeding on DGLA, but not other long-chain polyunsaturated fatty acids become sterile, partly due to excess apoptosis of germ cells. Our molecular, genetic, and biochemical studies of this process promise to shed light on the roles of polyunsaturated fatty acids in reproductive processes.
Deline M, Keller J, Rothe M, Schunck WH, Menzel R, Watts JL. Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C.elegans. Sci Rep. 2015 Oct 21;5:15417. doi: 10.1038/srep15417. PMID: 26486965
Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK. s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. Cell Metab. 2015 Oct 6;22(4):633-45. doi: 10.1016/j.cmet.2015.07.013. Epub 2015 Aug 27. PMID: 26321661.
Vrablik TL, Petyuk VA, Larson EM, Smith RD, Watts JL. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein. Biochim Biophys Acta. 2015 Oct;1851(10):1337-45. doi: 10.1016/j.bbalip.2015.06.004. Epub 2015 Jun 27. PMID: 26121959.
Hou, N., Choi, D.Y., Pather, K., Gutschmidt, A., Shi, X, Watts, JL, Hoppe, T., Taubert, S. (2014) Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. Proc. Natl. Acad. Sci. USA 111 (22) E2271-E2280.
Deline, M, Vrablik, TL, Watts, JL. Dietary Supplementation of Polyunsaturated Fatty Acids in Caenorhabditis elegans. Journal of Visualized Experiments 2013 Nov 29;(81). doi: 10.3791/50879.
Shi, X., Li, J., Zou, X., Greggain, J., Rodkaer, S.V., Faergeman, N.J., Liang, B., and& Watts, J.L. Regulation of lipid droplet size and phospholipid compostion by stearoyl-CoA desaturase. Journal of Lipid Research 54 (2013), 2504-2514.
Vrablik TL, Watts JL. Polyunsaturated fatty acid derived signaling in reproduction and development: Insights from Caenorhabditis elegans and Drosophila melanogaster. Mol Reprod Dev. 2013 Feb 25. doi: 10.1002/mrd.22167. [Epub ahead of print] PMID: 23440886
Webster CM, Deline ML, Watts JL. Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans. Dev Biol. 2013 Jan 1;373(1):14-25. doi: 10.1016/j.ydbio.2012.10.002. PMID:23064027
Vrablik TL, Watts JL. Emerging roles for specific fatty acids in developmental processes. Genes Dev. 2012 Apr 1;26(7):631-7. doi: 10.1101/gad.190777.112. PMID: 22474257
Lim MA, Selak MA, Xiang Z, Krainc D, Neve RL, Kraemer BC, Watts JL, Kalb RG. Reduced Activity of AMP-Activated Protein Kinase Protects against Genetic Models of Motor Neuron Disease. J Neurosci. 2012 Jan 18;32(3):1123-1141.
Walker AK, Jacobs RL, Watts JL, Rottiers V, Jiang K, Finnegan DM, Shioda T, Hansen M, Yang F, Niebergall LJ, Vance DE, Tzoneva M, Hart AC, Näär AM. A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell. 2011 Nov 11;147(4):840-52. Epub 2011 Oct 27.
Liang B, Ferguson K, Kadyk L, Watts JL. The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One. 2010 Mar 25;5(3):e9869.PMID: 20360843
Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Näär AM. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010 Jul 1;24(13):1403-17.PMID: 20595232
Kyleann K. Brooks, Bin Liang, Jennifer L. Watts (2009) "The Influence of Bacterial Diet on Fat Storage in C. elegans" PlosOne 4(10) e7545. PDF
Jennifer L. Watts (2009) "Fat Synthesis and Adiposity Regulation in Caenorhabditis elegans" Trends in Endocrinology and Metabolism 20: 58-65. PDF
Trisha J. Brock, John Browse and Jennifer L. Watts. “Fatty Acid Desaturation and the Regulation of Adiposity in Caenorhabditis elegans.” Genetics 176(2007) 865-875. PDF
Lena K. Schroeder, Susan Kremer, Maxwell J. Kramer, Erin Currie, Elizabeth Kwan, Jennifer L. Watts, Andrea L. Lawrenson and Greg Hermann. “Function of the Caenorhabditis elegans ABC transporter PGP-2 in the biogenesis of a lysosome-related fat storage organelle”. Mol Biol Cell 18 (2007) 995- 1008.PDF
Homare M. Kubagawa, Jennifer L. Watts, Chad Corrigan, Johnathan W. Edmonds, Elizabeth Sztul, John Browse, and Michael A. Miller. “Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo. Nature Cell Biology 8 (2006) 1143-1148. PDF
Fajun Yang, Bryan W. Vought, John S. Satterlee, Z.-Y. Jim Sun, Jennifer L. Watts, Rosalie DeBeaumont, R. Mako Saito, Sven G. Hyberts, Shaosong Yang, Christine Macol, Lakshmanan Iyer, Robert Tjian, Sander van den Heuvel, Anne Hart, Gerhard Wagner, and Anders M. Näär. “An ARC/ Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.” Nature 442 (2006) 700-704. PDF
Trisha J. Brock, John Browse, and Jennifer L. Watts. “Genetic Regulation of Unsaturated Fatty Acid Composition in C. elegans”PLOS Genetics 2 (2006) e108. PDF
Jennifer L. Watts and John Browse. "Dietary manipulation implicates lipid signaling in the maintenance of C. elegans germ cells" Developmental Biology 292(2006) 381-392. PDF
Amanda H. Kahn-Kirby, J.L.M Dantzker, John Browse, Cornelia I. Bargmann, and Jennifer L Watts. “Specific polyunsaturated fatty acids drive TRPV-dependent sensory signaling in vivo. Cell 119 (2004), 889-900. PDF
Kaveh Ashrafi, Francesca Y. Chang, Jennifer L. Watts, Andrew G. Fraser, Ravi S. Kamath, Julie Ahringer, and Gary Ruvkun. "Genome-wide RNAi analysis of C. elegans fat regulatory genes" Nature 421(2003) 268-272. PDF
Jennifer L. Watts, Eric Phillips, Katharine R. Griffing, and John Browse. "Deficiencies in C20 polyunsaturated fatty acids cause behavioral and developmental defects in C. elegans fat-3 mutants" Genetics 163 (2003) 581-589. PDF
Marina Kniazeva, Matt Sieber, Scott McCauley, Kang Zhang, Jennifer L. Watts, and Min Han. "Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in C. elegans." Genetics 163 (2003) 159-160.PDF
Jennifer L. Watts and John Browse. "Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans" Proc. Nat. Acad. Sci. USA 99 (2002) 5854-5859. PDF
James G. Wallis, Jennifer L. Watts, and John Browse. "Polyunsaturated fatty acid synthesis. What will they think of next?" Trends Biochem Sci. 27 (2002) 467-473 PDF
Jennifer L. Watts and John Browse. “A Palmitoyl-CoA-Specific D 9 Fatty Acid Desaturase from Caenorhabditis elegans” Biochem. Biophys. Res. Comm. 272 (2000) 263-269. PDF
Marlyse Peyou-Ndi, Jennifer L. Watts, John Browse. "Identification and Characterization of an Animal D12 Fatty Acid Desaturase from Caenorhabditis elegans" Archives of Biochemistry and Biophysics 376 (2000) 399-408. PDF
Jennifer L. Watts and John Browse. “Isolation and Characterization of a D5-Fatty Acid Desaturase from Caenorhabditis elegans” Archives of Biochemistry and Biophysics 362 (1999) 175-182. PDF