Clinical Metabolomics: Current state and future directions
Andrew N. Hoofnagle
Andrew N. Hoofnagle
Department of Laboratory Medicine and Pathology,
University of Washington
M.D., University of Colorado School of Medicine, Denver, CO, USA
Ph.D., University of Colorado at Boulder, Boulder, CO, USA
Resident, Clinical Pathology, Departments of Laboratory Medicine and Pathology
University of Washington Medical Center, Seattle, WA, USA
Chief Resident, Clinical Pathology, Departments of Laboratory Medicine and Pathology
University of Washington Medical Center, Seattle, WA, USA
Pablo A, Hoofnagle AN, Mathias PC. Listening to your mass spectrometer: An open-source toolkit to visualize mass spectrometer data. (2021) J Mass Spectrom Adv Clin Lab. 23:44-49.
Huang D, Chowdhury S, Wang H, Savage SR, Ivey RG, Kennedy JJ, Whiteaker JR, Lin C, Hou X, Oberg AL, Larson MC, Eskandari N, Delisi DA, Gentile S, Huntoon CJ, Voytovich UJ, Shire ZJ, Yu Q, Gygi SP, Hoofnagle AN, Herbert ZT, Lorentzen TD, Calinawan A, Karnitz LM, Weroha SJ, Kaufmann SH, Zhang B, Wang P, Birrer MJ, Paulovich AG. (2021) Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer. Cell Rep Med. 2(12):100471.
Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum BR, Thummel KE, Hoofnagle AN, de Boer IH. (2022) Validation of the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio as a biomarker of 25-hydroxyvitamin D3 clearance. J Steroid Biochem Mol Biol. 217:106047.
Hsu S, Prince DK, Williams K, Allen NB, Burke GL, Hoofnagle AN, Li X, Liu KJ, McClelland RL, Michos ED, Psaty BM, Shea SJ, Rice KM, Rotter JI, Siscovick D, Tracy RP, Watson KE, Kestenbaum BR, de Boer IH. Clinical and biomarker modifiers of vitamin D treatment response: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr. 115(3):914-924.
Sempos CT, Williams EL, Carter GD, Jones J, Camara JE, Burdette CQ, Hahm G, Nalin F, Duewer DL, Kuszak AJ, Merkel J, Hoofnagle AN, Lukas P, Cavalier É, Durazo-Arvizu RA, Crump PM, Popp C, Beckert C, Schultess J, Van Slooten G, Tourneur C, Pease C, Kaul R, Villarreal A, Ivison F, Fischer R, van den Ouweland JMW, Ho CS, Law EWK, Simard JN, Gonthier R, Holmquist B, Batista MC, Meadows S, Cox L, Jansen E, Khan DA, Robyak K, Creer MH, Kilbane M, Twomey PJ, Freeman J, Parker N, Yuan J, Fitzgerald R, Mushtaq S, Clarke MW, Breen N, Simpson C, Wise SA. (2022) Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions. Anal Bioanal Chem. 414(2):1015-1028.
10:45 - 11:00
11:00 - 12:00
Glucose metabolism and its signaling in cancer and immune regulation
林慧觀 Hui-Kuan Lin
Director of Prostate Cancer Center
Department of Cancer Biology
Wake Forest University School of Medicine
National Taiwan University, Taipei, Taiwan, Taiwan, BS, 1993, Pharmacy
National Taiwan University, Taipei, Taiwan, Taiwan, MS, 1995, Pharmacology
University of Rochester, Rochester, NY, PHD, 2002, Pathology (Cancer Biology)
Zhang, W., Wang, G., Xu, ZG., Tu, F., Dai, J., Chang, Y., Chen, Y., Lu, Y., Zeng, H., Cai, Z., Han, F., Xu, C., Jin, G., Sun, L., Pan, BS., Lai, SW., Hsu, CC., Xu, J., Chen, Z., Li, HY., Seth P., Hu, J., Zhang, X., Li, H., Lin, HK. Lactate is a natural suppressor of RLR signaling by targeting MAVS. Cell. 2019 Jun 27;178(1):176-189.e15. doi: 10.1016/j.cell.2019.05.003. Epub 2019 May 30.
Wang G, Long J, Gao Y, Zhang. W, HanF, XuC, SunL, YangSC, Lan J, HouZ, CaiZ, Jin G, Hsu CC, Wang YH, Hu J, Chen TY, Li H, Lee MG, Lin HK.SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis. Nat. Cell Biol. 2019 Feb;21(2):214-225.
Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D, Logothetis CJ, Hung MC, Zhang S, Lin HK. Pharmacological Inactivation of Skp2 SCF Ubiquitin Ligase Restricts Cancer Stem Cell Traits and Cancer Progression. Cell 154(3):556-68, 8/2013.
Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y, Hazle JD, Yu D, Wei W, Sarbassov D, Hung MC, Nakayama KI, Lin HK. The Skp2-SCF E3 Ligase Regulates Akt Ubiquitination, Glycolysis, Herceptin Sensitivity, and Tumorigenesis. Cell 149(5):1098-111, 5/2012.
Yang WL, Wang J, Chan CH, Lee SW, Campos AD, Lamothe B, Hur L, Grabiner BC, Lin X, Darnay BG, Lin HK. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science 325(5944):1134-1138, 8/2009.
12:00 - 14:00
12:00 - 14:00
13:00 - 14:20
Communication between cancer cells and immune cells during tumor progression
楊慕華 Muh-Hwa Yang
Chair professor of Institute of Clinical Medicine, Yang Ming Chiao Tung University
Institute of Clinical Medicine, National Yang Ming Chiao Tung University
M.D., National Yang-Ming University
Ph.D., National Yang-Ming University
Resident and clinical fellow of Division of Hematology-Oncology, Taipei Veterans General Hospital
Chen HY, Hsieh, CH, Lin PH, Chen YT, Hsu DS, Tai SK, Chu PY, Yang MH*. Snail regulated microRNA-21 suppresses NLRP3 inflammasome activity to enhance cisplatin resistance. J Immunother Cancer 2022;10:e004832.
Ou DL, Chen CW, Hsu CL, Chung CH, Feng ZR, Lee BS, Cheng AL, Yang MH*, Hsu C*. Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. J Immunother Cancer 2021;9:e001657.
Liao TT, Lin CC, Jiang JK, Yang SH, Teng HW, Yang MH*. Harnessing stemness and PD-L1 expression by AT-rich interaction domain-containing protein 3 in colorectal cancer. Theranostics 2020;10:6095-6112.
Li CF, Chen JY, Ho YH, Hsu WH, Wu, LC, Lan HY, Hsu DS, Tai SK, Chang YC*, Yang MH*. Snail-induced claudin-11 prompts collective migration for tumor progression. Nat Cell Biol 2019;21:251-262.
Hwang WL*, Lan HY, Cheng WY, Huang SC, Yang MH*. Tumor stem-Like cells-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer. J Hematol Oncol 2019;12:10.
14:30 - 15:00
14:30 - 16:40
15:00 - 15:10
15:10 - 15:50
Metabolomics Enables Precision Medicine
蕭明熙 Ming-Shi Shiao
Adjunct Professor, Graduate Institute of Traditional Medicine, National Yang Ming Chau Ton University, Taipei
Department Biomedical Sciences, Chang Gung University, Professor Emeritus
1974 -1978 Ph.D., Bioorganic Chemistry, Brown University, Providence, RI, USA
1968 -1972 B.S., Chemistry, National Taiwan University, Taipei, Taiwan
1991 Outstanding Research Award, National Science Council, Taiwan
1987, 1988 Outstanding Research Prize, Vocational Assistance Commission for Retired Servicemen, Taiwan
1983 Public Health Service International Research Fellowship, John E. Fogarty International Center, National Institute of Health, USA
15:50 - 16:30
Rapid Characterization and Imaging of Drugs and Potential Metabolic Disease Biomarkers on Human Skin with Ambient Ionization Tandem Mass Spectrometry
謝建台 Jentaie Shiea
國立中山大學化學系 (Chemistry, NSYSU)
國立中興大學化學系畢業(1977-1981)，美國蒙大拿州立大學 (Montana State Univ) 有機地球化學碩士及分析化學博士(1985-1991)，賓州州立大學 (Pennsylvania State Univ) 材料科學系博士後研究(1991)，美國蒙大拿州立大學訪問副教授(1995-1996)，美國加州大學洛杉磯分校(UCLA)訪問教授(2004-2005)，國立中山大學化學系副教授、教授、特聘教授(1991起)。
Skin, the largest organ of human body, plays a key role in protecting the body against environmental pathogens and with numerous glands under the skin continually releasing metabolites and wastes onto the skin’s surface. Even some of these metabolites may be potential biomarkers for diseases, current analytical techniques are unable to efficiently characterize them for the difficulties in sampling, sample pretreatment, and their presence in extremely low quantity. In this study, an ambient ionization mass spectrometric technique—thermal desorption electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) was developed and applied to rapidly characterize trace drugs and potential metabolic biomarkers on skin without sample pretreatment, blood withdrawals, or urine collection. A stainless steel probe was used to gently scrap the skin surface for noninvasively skin sampling; the probe was then inserted into the ionization source to thermally desorb the analytes on it. The analytes were subsequently delivered by a nitrogen stream into an electrospray plume, where the analytes were ionized by reacting with the charged solvent species in the plume. Each analysis took less than 30 seconds to complete. With the features of simple, rapid and highly sensitive, TD-ESI/MS/MS was applied to determine metabolites profiles of patients with different diseases and normal controls. The results are helpful in understanding the relationship between skin metabolites and diseases.
Several drugs for targeted therapy of lung cancer patients were detected on patients’ skin. Detection of these drugs on skin without blood withdrawals or urine collection has the advantages for rapidly evaluating the effectiveness of the drugs and determination of individual pharmacokinetic profiles of drug on skin has the potential for precision medicine. The influence of physical therapy on the neurotransmitters on skin was studied. It was found that different individuals reacted differently on physical therapy. For some patients, it was found that certain metabolites were successfully stimulated on skin by physical therapy.
To explore the distribution of a metabolite or drug on whole body skin, three dimensional molecular imaging of skin metabolites were constructed from the data generated by multiple probe sampling (1400 probes) and TD-ESI/MS/MS analysis. The color of each sampling spot was assigned based on the intensity of the targeted metabolite signals. The molecular imaging reveal the distribution of drugs and nonpolar metabolites such as cholesterol and squalene on the surface of whole body.
16:30 - 17:10
The laboratory evaluation of glucose and lipid metabolism from Biochemical perspectives
Tjin-Shing Jap, M.D.
葉振聲 Tjin-Shing Jap, M.D.
Professor, School of Medicine, National Yang Ming University Physician, Division of Endocrinology and Metabolism, Taipei-Veterans General Hospital, Physician, Division of Endocrinology Weigong Memo
Division of Endocrinology and Metabolism, Taipei Veterans General hospital 112
1. Chang WL, Huang CJ, Lei TH, Niu DM, Chiu CY, Jap TS (corresponding author). A novel mutation of KCNJ11 gene in a patient with permanent neonatal diabetes mellitus. Diabetes Res Clin Pract 2014, 104: e29-e32
2. Jap TS, Jenq SF, YC Wu, CT Chiu, HM Cheng. Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in Taiwan. Pancreas 2003, 27: 122-6.
4. Jap, TS, Ho LT, Justin GS Won. Insulin secretion and sensitivity in hyperthyroidism. Hormone and Metabolic Research 1989;21:261-6. (SCI)
5.Tai WH, Jap, TS, Ho LT. Comparison of glucose, glucagon and standard meal-induced insulin release in patients with newly onset non-insulin dependent diabetes mellitus. Chin Med J (Taipei) 1988;42:353-8