Young-Jai You, Ph.D.Assistant Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Telephone: 804-628-4905 (office)
Telephone: 804-628-4913 (lab)
- B.S., 1988, Yonsei University, Seoul
- M.S., 1991, Yonsei University, Seoul
- Ph.D., 2004, University of Texas Southwestern Medical Center at Dallas
- Scientist Development Grant, American Heart Association: Principal Investigator
- University of Texas Southwestern Medical Center at Dallas , Advisors: Drs. Melanie Cobb and Leon Avery
Genetics of appetite control in C. elegans
All organisms must adapt to the quality and quantity of food available in their environment. Human responses to food evolved in an environment where high-calorie food was scarce and precious. In our novel, nutritionally rich environment, improper control of appetite contributes to diseases from anorexia to the current epidemic of obesity. Despite extraordinary recent advances, the molecular mechanisms of appetite control are still poorly understood, partly because they are so complex.
Our lab aims to investigate the cellular and molecular mechanisms of appetite control in a simple model system, Caenorhabditis elegans. In past few years we have discovered that, just as in mammals, C. elegans appetite is promoted by hunger and suppressed by full-feeding; when starved, worms become hungry and increase feeding motions through a muscarinic acetylcholine receptor MAP kinase signaling pathway. When they are fed an excess of food after fasting, they are satiated, stop feeding and become quiescent through insulin, TGFb and cGMP signaling pathways. Increasing feeding motion by muscarinic signaling and decreasing appetite by signaling such as insulin show similarities not only in behavior but also in molecular mechanisms for the response to food, suggesting strong conservation between mammals and worms in controlling appetite.
Based on this conservation, we aim to establish in C. elegans a genetic model system to study appetite control. First, we will examine molecular mechanisms of appetite control by TGFb and cGMP signals; despite the molecular conservation of TGFb and cGMP between mammals and worms, their functions in food intake and appetite control are poorly understood in both. Second, we will examine the role of metabolism and fat storage in appetite control.
We anticipate that molecular mechanisms will be fundamentally similar to those of mammals, but simpler and therefore easier to unravel in worms. Furthermore, the powerful genetic tools available in the worm will allow rapid elucidation of new pathways, whose relevance to mammalian behavior can subsequently be tested.
You YJ, Kim J, Cobb M, Avery L. Starvation activates MAP kinase through the muscarinic acetylcholine pathway in Caenorhabditis elegans pharynx. Cell Metab. 2006 Apr;3(4):237-45. PubMed PMID: 16581001.
Kang C, You YJ, Avery L. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 2007 Sep 1;21(17):2161-71. PubMed PMID: 17785524; PubMed Central PMCID: PMC1950855.
You YJ, Kim J, Raizen DM, Avery L. Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab. 2008 Mar;7(3):249-57. PubMed PMID: 18316030.
van der Linden AM, Wiener S, You YJ, Kim K, Avery L, Sengupta P. The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A to regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis elegans. Genetics. 2008 Nov;180(3):1475-91. Epub 2008 Oct 1. PubMed PMID: 18832350; PubMed Central PMCID: PMC2581950.
Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV, Pack AI. Lethargus is a Caenorhabditis elegans sleep-like state. Nature. 2008 Jan 31;451(7178):569-72. Epub 2008 Jan 9. Erratum in: Nature. 2008 Jun 12;453(7197):952. PubMed PMID: 18185515.
Whitehurst AW, Wilsbacher JL, You YJ, Luby-Phelps K, Moore MS, Cobb MH. ERK2 enters the nucleus by a carrier-independent mechanism. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7496-501. PubMed PMID: 12032311; PubMed Central PMCID: PMC124259.