The major accomplishment of my scientific career has been to advance the idea that sphingolipids such as ceramides regulate nutrient homeostasis and contribute to diabetes and other metabolic diseases. The opinion was initially controversial and few publications other than my own appeared on the topic. Nonetheless, the data were robust and the therapeutic potential of the pathway obvious. Through research reports, review articles and invited seminars, our work has influenced the directions of new and established researchers and the number of publications containing the words ceramide and insulin has risen exponentially. Our research has been continuously funded since 2000 and our articles have been cited more than 11,700 times. Building upon our research discoveries, in 2015 I co-founded Centaurus Therapeutics, a biotechnology company that has developed novel dihydroceramide desaturase inhibitors to lower ceramides and ameliorate cardiometabolic disease. Our current research efforts seek to determine (a) the tissue-specific responses of sphingolipids towards the regulation of metabolism, (b) the intracellular targets that mediate their effects, and (c) the regulatory events controlling their accumulation. Moreover, (d) we seek to develop drugs targeting enzymes in the ceramide-synthesizing pathway, which we believe hold enormous potential in a broad spectrum of metabolic disorders.
As my research program developed, I had the opportunity to assume leadership roles within the diabetes research community. Indeed, I relish the opportunity to grow collaborative programs and enhance the success of junior faculty members. I’ve served as the chair of several national conferences in the diabetes arena (e.g. the Keystone Symposia on Lipid Biology and Lipotoxicity and the FASEB Science Research Conference on the Regulation of Glucose Metabolism), on the editorial board of various preeminent journals (e.g. Journal of Clinical Investigation), as the Director of the Singapore Diabetes Consortium, as the Director of the Duke-NUS Graduate School’s Metabolic Phenotyping Core (Singapore), and as the Director of the Metabolism and Inflammation Program at the Baker Heart and Diabetes Institute (Melbourne, Australia). After running laboratories abroad for 8 years, I returned to the USA and the University of Utah in 2016 to become the chair of a new Department of Nutrition and Integrative Physiology and the Co-Director (with Jared Rutter, HHMI) of the Diabetes and Metabolism Research Center. I am committed to the success of these endeavors, which have a major research focus on “translational metabolic health” and are tightly aligned. The university leadership is fully committed to these integrated programs and provides me with ample protected time to serve in these administrative capacities.
Professor Summers had been a dominant voice advancing the idea that sphingolipids such as ceramide, which are produced by over-nutrition and inflammation, contribute to insulin resistance and metabolic disease. The opinion was initially controversial, and few publications other than his appeared on the topic. Nonetheless, the data were robust and the therapeutic potential of the pathway obvious. His work has appeared in the highest impact journals (e.g. Nature Medicine, Cell Metabolism, Journal of Clinical Investigation and others) and have been cited over 8000 times. He has given over 100 presentations in at least 20 different countries, including keynote talks in Japan, Finland and the USA, and received over 10 million dollars in research grant support. His work has influenced the directions of new and established researchers and the number of publications containing the words ceramide and insulin has risen exponentially. His current group continues to explore the therapeutic potential of the pathway with an eye towards developing new therapies to treat diabetes and metabolic disease.
- Chaurasia B, Tippetts TS, Mayoral Monibas R, Liu J, Li Y, Wang L, Wilkerson JL, Sweeney CR, Pereira RF, Sumida DH, Maschek JA, Cox JE, Kaddai V, Lancaster GI, Siddique MM, Poss A, Pearson M, Satapati S, Zhou H, McLaren DG, Previs SF, Chen Y, Qian Y, Petrov A, Wu M, Shen X, Yao J, Nunes CN, Howard AD, Wang L, Erion MD, Rutter J, Holland WL, Kelley DE, Summers SA (2019). Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science, 365(6451), 386-392.
- Kiser PD, Kolesnikov AV, Kiser JZ, Dong Z, Chaurasia B, Wang L, Summers SA, Hoang T, Blackshaw S, Peachey NS, Kefalov VJ, Palczewski K (2019). Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. FASEB J, 33(4), 5782-5792.
- Poss AM Holland WL Summers (02/01/2019). Risky Lipids. Refining the Ceramide Score that Measures Cardiovascular Health. Eur Heart J.
- Kiser (01/2019). Conditoinal.
- Chaurasia B (01/2019). Targeting.
- Karanth (01/2019). Fox.
- Cai J, Pires KM, Ferhat M, Chaurasia B, Buffolo MA, Smalling R, Sargsyan A, Atkinson DL, Summers SA, Graham TE, Boudina S (2017). Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk. Cell Rep, 25(7), 1708-1717.e5.
- Chaurasia B, Holland WL, Summers SA (2018). Does This Schlank Make Me Look Fat? Trends Endocrinol Metab, 29(9), 597-599.
- Tippetts TS, Holland WL, Summers SA (2018). The ceramide ratio: a predictor of cardiometabolic risk. J Lipid Res, 59(9), 1549-1550.
- Holland WL, Summers SA (2019). Strong Heart, Low Ceramides. Diabetes, 67(8), 1457-1460.
- de Carvalho LP, Tan SH, Ow GS, Tang Z, Ching J, Kovalik JP, Poh SC, Chin CT, Richards AM, Martinez EC, Troughton RW, Fong AY, Yan BP, Seneviratna A, Sorokin V, Summers SA, Kuznetsov VA, Chan MY (2018). Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction. JACC Basic Transl Sci, 3(2), 163-175.
- An J, Wang L, Patnode ML, Ridaura VK, Haldeman JM, Stevens RD, Ilkayeva O, Bain JR, Muehlbauer MJ, Glynn EL, Thomas S, Muoio D, Summers SA, Vath JE, Hughes TE, Gordon JI, Newgard CB (2018). Physiological mechanisms of sustained fumagillin-induced weight loss. JCI Insight, 3(5).
- Summers SA (2018). Could Ceramides Become the New Cholesterol? Cell Metab, 27(2), 276-280.
- Chaurasia B, Summers SA (2017). Ceramides - Lipotoxic Inducers of Metabolic Disorders: (Trends in Endocrinology and Metabolism 26, 538-550; 2015). Trends Endocrinol Metab, 29(1), 66-67.
- Summer Sa (01/2018). Could ceramides become the new cholesterol? . Cell Metab.
- An J (01/2018). Physiological mechanisms of sustained fumagillin-induced weight loss. .
- Chaurasia B (01/2018). Does this Schlank make me look fat. Trends in Endocrinology and Metabolism.
- Holland WL (01/2018). Strong Heart.
- Tippetts (01/2018). The Ceramide Ratio.
- de (01/2018). Plasma.
- Cai (01/2018). Ablation.
- Meikle PJ (01/2017). Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. . 13(2), 79-91.
- Liu JJ (01/2017). Profiling of plasma metabolite suggests altered mitochondrial fuel usage and remodeling of sphingolipid metabolism in individuals with type 2 diabetes and kidney disease. . Kidney Int Rep, 2(3), 470-480.
- Liu JJ, Ghosh S, Kovalik JP, Ching J, Choi HW, Tavintharan S, Ong CN, Sum CF, Summers SA, Tai ES, Lim SC (2016). Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease. Kidney Int Rep, 2(3), 470-480.
- Chaurasia B (11/2016).
- Summers SA Goodpaster BH (06/01/2016). Rebuttal from Scott A. Summers and Bret H. Goodpaster. J Physiol, 594, 3175-6.
- Summers SA Goodpaster BH (06/01/2016). CrossTalk proposal: Intramyocellular ceramide accumulation does modulate insulin resistance. J Physiol, 594, 3167-70.
- Lee MH Goralczyk AG Kriszt R Ang XM Badowski C Li Y Summers SA Toh SA Yassin MS Shabbir A Sheppard A Raghunath M (02/01/2016). ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs. Sci Rep, 6, 21173.
- Lee MH (01/2016). ECM microenvironment unlocks down adipogenic potential of adult human bone marrow-derived MSCs. . 21173.
- Goodpaster B (01/2016). CrossTalk Proposal: Intramyocellular ceramides do not cause insulin resistance. . 594(12)316703170.
- Goodpaster B (01/2016). Rebuttal to CrossTalk Proposal: Intramyocellular ceramides do no cause insulin resistance. 594, 3167-3170.
- Park M (01/2016). Role for Ceramides, but NOT Sphingomyelins, as antagonists of insulin signaling and mitochondrial metabolism in C2C12 myotubes. . J Biol Chem, 291, 23978-23988.
- Bharath LP Ruan T Li Y Ravindran A Wan X Nhan JK Walker ML Deeter L Goodrich R Johnson E Munday D Mueller R Kunz D Jones D Reese V Summers SA Babu PV Holland WL Zhang QJ Abel ED Symons JD (10/01/2015). Ceramide-Initiated Protein Phosphatase 2A Activation Contributes to Arterial Dysfunction In Vivo. 64, 3914-26.
- Chaurasia B Summers SA (09/01/2015). Ceramides - Lipotoxic Inducers of Metabolic Disorders. 26(10), 538-50.
- Siddique MM Li Y Chaurasia B Kaddai VA Summers SA (06/01/2015). Dihydroceramides: From Bit Players to Lead Actors. 290(25), 15371-9.
- Teh JT Zhu WL Ilkayeva OR Li Y Gooding J Casey PJ Summers SA Newgard CB Wang M (06/01/2015). Isoprenylcysteine carboxylmethyltransferase regulates mitochondrial respiration and cancer cell metabolism. Oncogene, 34, 3296-304.
- Goodspeed D Seferovic MD Holland W Mcknight RA Summers SA Branch DW Lane RH Aagaard KM (03/01/2015). Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. 29(3), 807-19.
- Barbarroja N Rodriguez-Cuenca S Nygren H Camargo A Pirraco A Relat J Cuadrado I Pellegrinelli V Medina-Gomez G Lopez-Pedrera C Tinahones FJ Symons JD Summers SA Oresic M Vidal-Puig A (03/01/2015). Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function. 64, 1180-92.
- Sinha RA Farah BL Singh BK Siddique MM Li Y Wu Y Ilkayeva OR Gooding J Ching J Zhou J Martinez L Xie S Bay BH Summers SA Newgard CB Yen PM (03/01/2014). Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. 59, 1366-80.
- Chavez JA Siddique MM Wang ST Ching J Shayman JA Summers SA (01/01/2014). Ceramides and glucosylceramides are independent antagonists of insulin signaling. 289, 723-34.
- Chua EC Shui G Lee IT Lau P Tan LC Yeo SC Lam BD Bulchand S Summers SA Puvanendran K Rozen SG Wenk MR Gooley JJ (08/01/2013). Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans. Proc Natl Acad Sci U S A, 110, 14468-73.
- Siddique MM Li Y Wang L Ching J Mal M Ilkayeva O Wu YJ Bay BH Summers SA (05/01/2013). Ablation of dihydroceramide desaturase 1, a therapeutic target for the treatment of metabolic diseases, simultaneously stimulates anabolic and catabolic signaling. Mol Cell Biol, 33, 2353-69.
- Kolak M Gertow J Westerbacka J Summers SA Liska J Franco-Cereceda A Orei M Yki-Jrvinen H Eriksson P Fisher RM (10/01/2012). Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue. Lipids Health Dis, 11, 115.
- Siddique MM Bikman BT Wang L Ying L Reinhardt E Shui G Wenk MR Summers SA (09/01/2012). Ablation of dihydroceramide desaturase confers resistance to etoposide-induced apoptosis in vitro. PLoS One, 7, e44042.
- Sinha RA You SH Zhou J Siddique MM Bay BH Zhu X Privalsky ML Cheng SY Stevens RD Summers SA Newgard CB Lazar MA Yen PM (07/01/2012). Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. 122, 2428-38.
- Zhang QJ Holland WL Wilson L Tanner JM Kearns D Cahoon JM Pettey D Losee J Duncan B Gale D Kowalski CA Deeter N Nichols A Deesing M Arrant C Ruan T Boehme C McCamey DR Rou J Ambal K Narra KK Summers SA Abel ED Symons JD (06/01/2012). Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. 61(7), 1848-59.
- Chavez JA Summers SA (05/01/2012). A ceramide-centric view of insulin resistance. Cell Metab, 15, 585-94.
- Bikman BT Guan Y Shui G Siddique MM Holland WL Kim JY Fabris G Wenk MR Summers SA (05/01/2012). Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. 287, 17426-37.
- Bikman BT Summers SA (11/01/2011). Ceramides as modulators of cellular and whole-body metabolism. 121, 4222-30.
- Bikman BT Summers SA (09/01/2011). Sphingolipids and hepatic steatosis. Adv Exp Med Biol, 721, 87-97.
- Holland WL Bikman BT Wang LP Yuguang G Sargent KM Bulchand S Knotts TA Shui G Clegg DJ Wenk MR Pagliassotti MJ Scherer PE Summers SA (05/01/2011). Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. 121, 1858-70.
- Holland WL Miller RA Wang ZV Sun K Barth BM Bui HH Davis KE Bikman BT Halberg N Rutkowski JM Wade MR Tenorio VM Kuo MS Brozinick JT Zhang BB Birnbaum MJ Summers SA Scherer PE (01/01/2011). Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med, 17, 55-63.
- Summers SA (07/01/2010). Sphingolipids and insulin resistance: the five Ws. Curr Opin Lipidol, 21, 128-35.
- Chavez JA Summers SA (02/01/2010). Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochim Biophys Acta, 1801, 252-65.
- Fujii N Ho RC Manabe Y Jessen N Toyoda T Holland WL Summers SA Hirshman MF Goodyear LJ (10/01/2008). Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. 57, 2958-66.
- Holland WL Summers SA (06/01/2008). Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev, 29, 381-402.
- Meikle P (10/2016). [Review].
- Wilkerson JL, Summers SA, Holland WL (2019). Listen to your heart when ceramide's calling for higher glucose. [Letter to the editor]. EBioMedicine, 41, 3-4.
- Summers (01/2019). Metabolic. n/a.
- Wilkerson (01/2019). Listen. n/a.
- Verkerke (01/2019). Phospholipid. n/a.
- Poss (01/2019). Risky. n/a.
- Funai (01/2019). Reign. n/a.
- Summers SA (08/01/2015). The ART of Lowering Ceramides. Cell Metab (22, pp. 195-6). Cell metabolism.
- Raichur S, Wang ST, Chan PW, Li Y, Ching J, Chaurasia B, Dogra S, hman MK, Takeda K, Sugii S, Pewzner-Jung Y, Futerman AH, Summers SA (2014). CerS2 Haploinsufficiency Inhibits β-Oxidation and Confers Susceptibility to Diet-Induced Steatohepatitis and Insulin Resistance. Cell Metab (20(5), p. 919). United States.
- Summers SA Matijevic A Almond MK (07/01/2004). Successful re-introduction of recombinant human erythropoietin following antibody induced pure red cell aplasia. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (19, pp. 2137-9). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.