Scott Summers

Scott Summers, PhD

Academic Information

Departments Adjunct - Biochemistry

Academic Office Information

scott.a.summers@health.utah.edu

Lab

The major accomplishment of my scientific career has been to advance the idea that sphingolipids such as ceramides regulate nutrient homeostasis and contribute to the chronic diseases associated with obesity and dyslipidemia, including diabetes and its complications. 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 exploring the link between ceramides and metabolic disease has risen exponentially. Our current research evaluates (a) the tissue-specific effects of sphingolipids in 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 associated with obesity. In 2015 I co-founded Centaurus Therapeutics, a biotechnology company that is developing novel dihydroceramide desaturase inhibitors to lower ceramides and ameliorate cardiometabolic disease.

As my research program developed, I had the opportunity to assume leadership roles within the diabetes and metabolism research community. I relish the opportunity to grow collaborative programs and enhance the success of junior faculty members and graduate and postdoctoral trainees. 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 Utah Diabetes and Metabolism Research Center (UDMRC). Both units have shown impressive growth, as we have sought to expand our programs and establish the University of Utah as a center of diabetes and metabolism research excellence. Indeed, since I assumed the mantle of leadership, the UDMRC has developed exceptionally strong interest groups focused on (i) Metabolism and (ii) Health Behaviors, while adding numerous accomplished researchers to our already strong faculty base. We’ve increased the university’s diabetes and metabolism funding portfolio, obtained or renewed fivetraining grants for junior investigators wishing to study these disciplines, developed new summer training programs for students interested in a biomedical research careers, greatly expanded our pilot and feasibility programs, and developed several research cores that catalyze innovation and discovery. The university gives me ample protected time to conduct research while working on these other endeavors.

Research Statement

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.

Selected Publications

Journal Article

  1. Holland WL, Summers S (2018). Strong Heart, Low Ceramides. Diabetes, 67(8), 1457-1460.
  2. Kiser PD, Kolesnikov AV, Kiser JZ, Dong Z, Chaurasia B, Wang L, Summers SA, Hoang T, Blackshaw S, Peachey NS, Kefalov VJ, Palczewski (2019). Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. FASEB journal, 33(4), 5782-5792.
  3. Tippetts TS, Holland WL, Summers S (2018). The ceramide ratio: a predictor of cardiometabolic risk. Journal of lipid research, 59(9), 1549-1550.
  4. 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 S (2019). Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science (New York, N.Y.), 365(6451), 386-392.
  5. Chaurasia B, Holland WL, Summers S (2018). Does This Schlank Make Me Look Fat?. Trends in endocrinology and metabolism, 29(9), 597-599.
  6. Chaurasia B, Summers S (2018). Ceramides - Lipotoxic Inducers of Metabolic Disorders: (Trends in Endocrinology and Metabolism 26, 538-550; 2015). Trends in endocrinology and metabolism, 29(1), 66-67.
  7. Summers S (2018). Could Ceramides Become the New Cholesterol?. Cell metabolism, 27(2), 276-280.
  8. Cai J, Pires KM, Ferhat M, Chaurasia B, Buffolo MA, Smalling R, Sargsyan A, Atkinson DL, Summers SA, Graham TE, Boudina (2018). Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk. Cell reports, 25(7), 1708-1717.e5.
  9. 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 C (2018). Physiological mechanisms of sustained fumagillin-induced weight loss. JCI insight, 3(5),
  10. 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 M (2018). Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction. JACC. Basic to translational science, 3(2), 163-175.
  11. Liu JJ, Ghosh S, Kovalik JP, Ching J, Choi HW, Tavintharan S, Ong CN, Sum CF, Summers SA, Tai ES, Lim S (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 international reports, 2(3), 470-480.
  12. Lee MH, Goralczyk AG, Kriszt R, Ang XM, Badowski C, Li Y, Summers SA, Toh SA, Yassin MS, Shabbir A, Sheppard A, Raghunath (2016). ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs. Scientific reports, 6, 21173.
  13. 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 S (2011). Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. 121, 1858-70.
  14. Poss AM, Holland WL, Summer (2019). Risky Lipids. Refining the Ceramide Score that Measures Cardiovascular Health. European heart journal,
  15. An (2018). Physiological mechanisms of sustained fumagillin-induced weight loss.
  16. Kise (2019). Conditoinal.
  17. Bikman BT, Summers S (2011). Ceramides as modulators of cellular and whole-body metabolism. 121, 4222-30.
  18. Fujii N, Ho RC, Manabe Y, Jessen N, Toyoda T, Holland WL, Summers SA, Hirshman MF, Goodyear L (2008). Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice. 57, 2958-66.
  19. Chaurasia (2018). Does this Schlank make me look fat. Trends in Endocrinology and Metabolism.
  20. Holland W (2018). Strong Heart.
  21. Chavez JA, Summers S (2010). Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochimica et biophysica acta, 1801, 252-65.
  22. 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 (2015). Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function. 64, 1180-92.
  23. Chavez JA, Summers S (2012). A ceramide-centric view of insulin resistance. Cell metabolism, 15, 585-94.
  24. Chavez JA, Siddique MM, Wang ST, Ching J, Shayman JA, Summers S (2014). Ceramides and glucosylceramides are independent antagonists of insulin signaling. 289, 723-34.
  25. Teh JT, Zhu WL, Ilkayeva OR, Li Y, Gooding J, Casey PJ, Summers SA, Newgard CB, Wang (2015). Isoprenylcysteine carboxylmethyltransferase regulates mitochondrial respiration and cancer cell metabolism. Oncogene, 34, 3296-304.
  26. Goodspeed D, Seferovic MD, Holland W, Mcknight RA, Summers SA, Branch DW, Lane RH, Aagaard K (2015). Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. 29(3), 807-19.
  27. 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 P (2014). Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. 59, 1366-80.
  28. Goodpaster (2016). Rebuttal to CrossTalk Proposal: Intramyocellular ceramides do no cause insulin resistance. 594, 3167-3170.
  29. Chaurasia (2019). Targeting.
  30. Ca (2018). Ablation.
  31. Bikman BT, Guan Y, Shui G, Siddique MM, Holland WL, Kim JY, Fabriàs G, Wenk MR, Summers S (2012). Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. 287, 17426-37.
  32. Holland WL, Summers S (2008). Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocrine reviews, 29, 381-402.
  33. Goodpaster (2016). CrossTalk Proposal: Intramyocellular ceramides do not cause insulin resistance. 594(12)316703170,
  34. 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 J (2012). Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. 61(7), 1848-59.
  35. Summers SA, Goodpaster B (2016). CrossTalk proposal: Intramyocellular ceramide accumulation does modulate insulin resistance. The Journal of physiology, 594, 3167-70.
  36. 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 P (2012). Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. 122, 2428-38.
  37. Summers S (2010). Sphingolipids and insulin resistance: the five Ws. Current opinion in lipidology, 21, 128-35.
  38. Meikle P (2017). Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. 13(2), 79-91.
  39. Siddique MM, Li Y, Wang L, Ching J, Mal M, Ilkayeva O, Wu YJ, Bay BH, Summers S (2013). Ablation of dihydroceramide desaturase 1, a therapeutic target for the treatment of metabolic diseases, simultaneously stimulates anabolic and catabolic signaling. Molecular and cellular biology, 33, 2353-69.
  40. Chaurasia, (2016).
  41. Chaurasia B, Summers S (2015). Ceramides - Lipotoxic Inducers of Metabolic Disorders. 26(10), 538-50.
  42. Siddique MM, Li Y, Chaurasia B, Kaddai VA, Summers S (2015). Dihydroceramides: From Bit Players to Lead Actors. 290(25), 15371-9.
  43. Tippett (2018). The Ceramide Ratio.
  44. Kolak M, Gertow J, Westerbacka J, Summers SA, Liska J, Franco-Cereceda A, Ore'i¿ M, Yki-Järvinen H, Eriksson P, Fisher R (2012). Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue. Lipids in health and disease, 11, 115.
  45. 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 J (2015). Ceramide-Initiated Protein Phosphatase 2A Activation Contributes to Arterial Dysfunction In Vivo. 64, 3914-26.
  46. d (2018). Plasma.
  47. Summers SA, Goodpaster B (2016). Rebuttal from Scott A. Summers and Bret H. Goodpaster. The Journal of physiology, 594, 3175-6.
  48. 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 P (2011). Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nature medicine, 17, 55-63.
  49. Siddique MM, Bikman BT, Wang L, Ying L, Reinhardt E, Shui G, Wenk MR, Summers S (2012). Ablation of dihydroceramide desaturase confers resistance to etoposide-induced apoptosis in vitro. PloS one, 7, e44042.
  50. Liu J (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 international reports, 2(3), 470-480.
  51. Summer S (2018). Could ceramides become the new cholesterol?. Cell metabolism,
  52. Lee M (2016). ECM microenvironment unlocks down adipogenic potential of adult human bone marrow-derived MSCs. 21173,
  53. Karant (2019). Fox.
  54. Bikman BT, Summers S (2011). Sphingolipids and hepatic steatosis. Advances in experimental medicine and biology, 721, 87-97.
  55. Park (2016). Role for Ceramides, but NOT Sphingomyelins, as antagonists of insulin signaling and mitochondrial metabolism in C2C12 myotubes. The Journal of biological chemistry, 291, 23978-23988.
  56. 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 J (2013). Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans. Proceedings of the National Academy of Sciences of the United States of America, 110, 14468-73.

Review

  1. Meikle, (2016).

Letter

  1. Wilkerson JL, Summers SA, Holland W (2019). Listen to your heart when ceramide's calling for higher glucose. EBioMedicine, 41, 3-4.

Other

  1. Raichur S, Wang ST, Chan PW, Li Y, Ching J, Chaurasia B, Dogra S, Öhman MK, Takeda K, Sugii S, Pewzner-Jung Y, Futerman AH, Summers S (2014). CerS2 Haploinsufficiency Inhibits ß-Oxidation and Confers Susceptibility to Diet-Induced Steatohepatitis and Insulin Resistance. Cell metabolism, 20(5), 919.
  2. Pos (2019). Risky.
  3. Verkerk (2019). Phospholipid.
  4. Summer (2019). Metabolic.
  5. Funa (2019). Reign.
  6. Summers S (2015). The ART of Lowering Ceramides. Cell metabolism, 22, 195-6.
  7. Wilkerso (2019). Listen.
  8. Summers SA, Matijevic A, Almond M (2004). Successful re-introduction of recombinant human erythropoietin following antibody induced pure red cell aplasia. 19, 2137-9.