Jonathan Long

Jonathan Long, PhD, Associate Professor, Department of Pathology, Stanford University 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):

  1. Wei W, Riley NM, Yang AC, Kim JT, Terrell SM, Li VL, Garcia-Contreras M, Bertozzi CR, Long JZ. Cell type-selective secretome profiling in vivo. Nat Chem Biol. 2021 Mar;17(3):326-334. doi: 10.1038/s41589-020-00698-y. PMID: 33199915; PMCID: PMC7904581. 

  2. Kim JT, Jedrychowski MP, Wei W, Fernandez D, Fischer CR, Banik SM, Spiegelman BM, Long JZ. A Plasma Protein Network Regulates PM20D1 and N-Acyl Amino Acid Bioactivity. Cell Chem Biol. 2020 Sep 17;27(9):1130-1139.e4. doi: 10.1016/j.chembiol.2020.04.009. PMID: 32402239; PMCID: PMC7502524. [Cites P30] 

  3. Kim JT, Terrell SM, Li VL, Wei W, Fischer CR, Long JZ. Cooperative enzymatic control of N-acyl amino acids by PM20D1 and FAAH. Elife. 2020 Apr 9;9:e55211. doi: 10.7554/eLife.55211. PMID: 32271712; PMCID: PMC7145423. [Cites P30] 

  4. Kim JT, Li VL, Terrell SM, Fischer CR, Long JZ. Family-wide Annotation of Enzymatic Pathways by Parallel In Vivo Metabolomics. Cell Chem Biol. 2019 Nov21; 26(11): 1623-29. PMID: 31587987.  

  5. Lin H, Long JZ, Roche AM, Svensson KJ, Dou FY, Chang MR, Strutzenberg T, Ruiz C, Cameron MD, Novick SJ, Berdan CA, Louie SM, Nomura DK, Spiegelman BM, Griffin PR, Kamenecka TM. Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration. J Med Chem. 2018 Apr 12;61(7):3224-3230. doi: 10.1021/acs.jmedchem.8b00029. PMID: 29533650; PMCID: PMC6335027. 

  6. Ezran C, Liu S, Chang S, Ming J, Guethlein LA, Wang MFZ, Dehghannasiri R, Olivieri J, Frank HK, Tarashansky A, Koh W, Jing Q, Botvinnik O, Antony J; Tabula Microcebus Consortium; Pisco AO, Karkanias J, Yang C, Ferrell JE Jr, Boyd SD, Parham P, Long JZ, Wang B, Salzman J, De Vlaminck I, Wu AR, Quake SR, Krasnow MA. Mouse lemur cell atlas informs primate genes, physiology and disease. Nature. 2025 Aug;644(8075):185-196. doi: 10.1038/s41586-025-09114-8. Epub 2025 Jul 30. PMID: 40739355; PMCID: PMC12328237. 

  7. Wiggenhorn AL, Abuzaid HZ, Coassolo L, Li VL, Tanzo JT, Wei W, Lyu X, Svensson KJ, Long JZ. A class of secreted mammalian peptides with potential to expand cell-cell communication. Nat Commun. 2023 Dec 8;14(1):8125. doi: 10.1038/s41467-023-43857-0. PMID: 38065934; PMCID: PMC10709327. 

  8. Wei W, Riley NM, Lyu X, Shen X, Guo J, Raun SH, Zhao M, Moya-Garzon MD, Basu H, Sheng-Hwa Tung A, Li VL, Huang W, Wiggenhorn AL, Svensson KJ, Snyder MP, Bertozzi CR, Long JZ. Organism-wide, cell-type-specific secretome mapping of exercise training in mice. Cell Metab. 2023 Jul. PMID: 37141889; PMCID: PMC10524249. 

  9. Xiao S, Li VL, Lyu X, Chen X, Wei W, Abbasi F, Knowles JW, Tung AS, Deng S, Tiwari G, Shi X, Zheng S, Farrell L, Chen ZZ, Taylor KD, Guo X, Goodarzi MO, Wood AC, Chen YI, Lange LA, Rich SS, Rotter JI, Clish CB, Tahir UA, Gerszten RE, Benson MD, Long JZ. Lac-Phe mediates the effects of metformin on food intake and body weight. Nat Metab. 2024 Apr;6(4):659-669. doi: 10.1038/s42255-024-00999-9. Epub 2024 Mar 18. PMID: 38499766; PMCID: PMC11062621. 

  10. Xiao S, Li VL, Long JZ. Lac-Phe (N-lactoyl-phenylalanine). Trends Endocrinol Metab. 2024 Aug;35(8):758-759. doi: 10.1016/j.tem.2024.05.007. Epub 2024 Jul 13. PMID: 39137723; PMCID: PMC11446501. 

  11. Wei W, Lyu X, Markhard AL, Fu S, Mardjuki RE, Cavanagh PE, Zeng X, Rajniak J, Lu N, Xiao S, Zhao M, Moya-Garzon MD, Truong SD, Chou JC, Wat LW, Chidambaranathan-Reghupaty S, Coassolo L, Xu D, Shen F, Huang W, Ramirez CB, Jang C, Li L, Svensson KJ, Fischbach MA, Long JZ. PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity. Nature. 2024 Sep;633(8028):182-188. doi: 10.1038/s41586-024-07801-6. Epub 2024 Aug 7. PMID: 39112712; PMCID: PMC11374699. 

  12. Li VL, Xiao S, Schlosser P, Scherer N, Wiggenhorn AL, Spaas J, Tung AS, Karoly ED, Köttgen A, Long JZ. SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans. Nat Commun. 2024 Aug 12;15(1):6895. doi: 10.1038/s41467-024-51174-3. PMID: 39134528; PMCID: PMC11319466. 

  13. Moya-Garzon MD, Wang M, Li VL, Lyu X, Wei W, Tung AS, Raun SH, Zhao M, Coassolo L, Islam H, Oliveira B, Dai Y, Spaas J, Delgado-Gonzalez A, Donoso K, Alvarez-Buylla A, Franco-Montalban F, Letian A, Ward CP, Liu L, Svensson KJ, Goldberg EL, Gardner CD, Little JP, Banik SM, Xu Y, Long JZ. A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites. Cell. 2025 Jan 9;188(1):175-186.e20. doi: 10.1016/j.cell.2024.10.032. Epub 2024 Nov 12. PMID: 39536746; PMCID: PMC11724754.