Jonathan Long, Assistant Professor, Pathology, Stanford School of Medicine
Research Description: The long-term goal of the Long Laboratory is to discover new metabolite signaling pathways and to identify the enzymes, transporters, and receptors that regulate their signaling in mammalian metabolism and physiology. To accomplish these goals, we use a unique and multidisciplinary approach that combines synthetic chemistry, biochemistry, mass spectrometry, and genetics to uncover new metabolite signaling pathways directly in complex organismal settings. In recent years, we have mapped entire branches of previously unknown bioactive metabolites and identified their functions in mammalian physiology, including a circulating PM20D1/N-acyl amino acid pathway in blood that regulates energy metabolism. We hope to translate these discoveries into pharmacologically tractable opportunities (e.g., enzyme inhibitors, transporter antagonists, or receptor modulators) for therapeutic intervention in obesity or associated metabolic disorders including diabetes and cardiovascular disease.
Selected relevant publications (Stanford DRC members are in BOLD):
- Long JZ, Svensson KJ, Bateman LA, Lin H, Kamenecka T, Lokurkar IA, Lou J, Rao RR, Chang MR, Jedrychowski MP, Paulo JA, Gygi SP, Griffin PR, Nomura DK, Spiegelman BM. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria. Cell. 2016 Jul 14;166(2):424-35.
- Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X, Rao RR, Lou J, Lokurkar I, Baur W, Castellot JJ Jr, Rosen ED, Spiegelman BM. A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014 May 6;19(5):810-20.
- Long JZ, Cisar JS, Milliken D, Niessen S, Wang C, Trauger SA, Siuzdak G, Cravatt BF. Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids. Nat Chem Biol. 2011 Sep 18;7(11):763-5.
- Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, Pavón FJ, Serrano AM, Selley DE, Parsons LH, Lichtman AH, Cravatt BF. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44.”