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Robert N. Helsley, PhD

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859-218-1608
robert.helsley@uky.edu
741 S. Limestone, BBSRB B347, Lexington, KY 40536

Positions

  • Assistant Professor

College Unit(s)

Other Affiliation(s)
  • Internal Medicine - Endocrinology
  • CVRC - Core Faculty

Biography and Education

Summary:

Bachelors of Science (Miami, OH); PhD (U. of Kentucky)
Hometown: Monroe, OH

Selected Publications

  1. Tranter, M., Helsley, R.N., Paulding, W., McGuinness, M., Brokamp, C., Haar, L., Ren, X., and Jones, W.K. (2011) Coordinated post-transcriptional regulation of the Hsp70.3 gene by micro-RNA and alternative polyadenylation. Journal of Biological Chemistry. 286(34): 29828-37. PMID: 21757701
  2. Park, S-H., Sui, Y., Gizard, F., Xu, J., Pilier-Rios, J., Helsley, R.N., Han, S-S., and Zhou, C. (2012) Myeloid-specific IKKβ deficiency decreases atherosclerosis in LDL receptor-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 32(12): 2869-76. PMID: 23023371
  3. Helsley, R.N.*, Sui, Y.*, Ai, N., Park, S-H., Welsh, W.J., and Zhou, C. (2013) Pregnane x receptor mediates dyslipidemia induced by the HIV protease inhibitor amprenavir in mice. Molecular Pharmacology. 83(6):1190-9. PMID: 23519392
  4. Sui, Y., Park, S-H., Helsley, R.N., Sunkara, M., Gonzalez, F.J., Morris, A.J., and Zhou, C. (2014) Bisphenol A increases atherosclerosis in pregnane x receptor-humanized ApoE deficient mice. Journal of the American Heart Association. 3(2): e000492. PMID: 24755147
  5. Sui, Y., Park, S.H., Xu, J., Monette, S., Helsley, R.N., Han, S-S., and Zhou, C. (2014) IKKβ links vascular inflammation to obesity and atherosclerosis. Journal of Experimental Medicine. 211(5): 869-886. PMID: 24799533
  6. Sui, Y.*, Helsley, R.N.*, Park, S.H., Song, X., Liu, Z., and Zhou, C. (2015) Intestinal PXR links xenobiotic exposure and hypercholesterolemia. Molecular Endocrinology. 29(5): 765-776. PMID: 25811240
  7. Helsley, R.N., Sui, Y., Park, S-H., Liu, Z., Lee, R.G., Zhu, B., Kern, P.A., and Zhou, C. (2016) Targeting IKKβ in adipocyte lineage cells for treatment of obesity and metabolic dysfunctions. Stem Cells. 34(7): 1883-95. PMID: 26991836
  8. Park, S-H., Liu, Z., Sui, Y., Helsley, R.N., Zhu, B., Powell, D.K., Kern, P.A., and Zhou, C. (2016) IKKβ is essential for adipocyte survival and adaptive adipose remodeling in obesity. Diabetes. 65(6): 1616-29. PMID: 26993069
  9. Helsley, R.N. and Zhou, C. (2017) Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view. Environ Epigenet. 3(4): 1-15   PMID: 29119010
  10. Ferguson, D., Zhang, J., Davis, M.A., Helsley, R.N., et al. (2017) The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis. J Lipid Res. 58(2): 420-432. PMID: 27941027
  11. Schugar, R.C., Shih, D.M., Warrier, M., Helsley, R.N., et al. (2017) The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue. Cell Rep. 19(12): 2451-2461. PMID: 28683320
  12. Gromovsky, A.D., Schugar, R.C., Brown, A.L., Helsley, R.N., et al (2018) Δ-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators. Arterioscler Thromb Vasc Biol. 38(1): 218-231. PMID: 29074585
  13. Gwag, T., Meng, Z., Sui, Y., Helsley, R.N., Park, S.H., Wang, S., Greenberg, R.N., and Zhou, C. (2019) Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis. J Hepatol. 70(5): 930-940. PMID: 30677459
  14. Helsley, R.N., Venkateshwari, V., Brown, A.L, et al (2019) Obesity-Linked Suppression of Membrane-Bound O-Acyltransferase 7 (MBOAT7) Drives Non-Alcoholic Fatty Liver Disease. eLife. 17;8e49882. PMID: 31621579
  15. Anthony, S.R., Guarnieri, A.R., Gozdiff, A., Helsley, R.N., Owens, A.P., and Tranter, M. (2019) Mechanisms Linking Adipose Tissue Inflammation to Cardiac Hypertrophy and Fibrosis. Clin Sci. 133(22):2329-2344. PMID: 31777927
  16. Brown, A.L., Conrad, K., Allende, D.S., Gromovsky, A.D., Neumann, C., Owens, P.A., Tranter, M., and Helsley, R.N. (2019) Choline Supplementation Attenuates High Fat Diet-Induced Hepatocellular Carcinoma (HCC) in Mice. J Nutr. 150(4):775-783. PMID: 31851339
  17. Helsley, R.N. and Softic, S. (2020) Fructose metabolism by the guts cuts liver fat. J Mol Med. 98(5):733-734. PMID: 32318746
  18. Pathak, P., Helsley, R.N., Brown, A.L., Buffa, J.A., et al. (2020) Small Molecule Inhibition of Gut Microbial Choline Trimethylamine Lyase Activity Alters Host Cholesterol and Bile Acid Metabolism. Am J Physiol Heart Circ Physiol. 318(6):H1474-1486 PMID:  32330092
  19. Anthony, S.R., Guarnieri, A., Lanzillotta, L., Gozdiff, A., Green, L.C., O’Grady, K., Helsley, R.N., Owens, P.A., and Tranter, M. (2020) HuR Expression in Adipose Tissue Mediates Energy Expenditure and Acute Thermogenesis Independent of UCP1 Expression. Adipocyte. 9(1): 335-345 PMID: 32713230
  20. Helsley, R.N.*, Moreau, F.*, Gupta, M.K., Radulescu, A, DeBosch, B., and Softic, S. (2020) Tissue-Specific Fructose Metabolism in Obesity and Diabetes. Curr Diab Rep. 20(11):64 PMID: 33057854
  21. Damen, M.S.M.A, Stankiewicz, T., Park, S-H., Helsley, R.N., et al. (2021) Non-hematopoietic IL-4Ra expression contributes to fructose-driven obesity and metabolic sequelae. Int J Obes (Lond). Doi: 10.1038/s41366-021-00902-6. PMID: 34302121
  22. Park, S.H., Helsley, R.N., et al. (2021) A Luminescence-Based Protocol for Assessing Fructose Metabolism via Quantification of Ketohexokinase Enzymatic Activity in Mouse or Human Hepatocytes. STAR Protoc. Doi: 10.1016/j.xpro.2021.100731. PMCID: PMC8361265
  23. Schugar, R.C., Gliniak, C.M., Osborn, L.J., Massey, W., Sangwan, N., Horak, A., Banerjee, R., Orabi, D., Helsley, R.N., et al. (2022) Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms. eLife. Doi: 10.7554/eLife.63998 PMID: 35072627
  24. Helsley, R.N.*, Miyata, T.*, Kadam, A.*, et al (2022) Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice. eLife. Doi: 10.7554/eLife.76554 PMID: 35084335
  25. Couch, S.C., Helsley, R.N., et al. (2022) Design and rational for the supermarket and web-based intervention targeting nutrition (SuperWIN) for cardiovascular risk reduction trial. Am Heart J. 248:21-34. PMID: 35218725
  26. Steen, D., Helsley, R.N., et al. (2022) Efficacy of Supermarket and Web-based Interventions for Improving Dietary Quality: A Randomized, Controlled Trial. Nat Med. PMID: 36456831
  27. Inci, M.K., Park, S.H., Helsley, R.N., et al. (2022) Fructose Impairs Fat Oxidation: Implications for the Mechanism of Western-Diet Induced NAFLD. J Nutr Biochem. PMID: 36403701
  28. Helsley, R.N., Park, S-H., Vekaria, V., et al. (2023) Ketohexokinase-C Mediates Global Protein Acetylation to Decrease Carnitine Palmitoyltransferase 1a Mediated Fatty Acid Oxidation. J Hepatol. PMID: 36822479
  29. Benson, T.W., Conrad, K.A., Li, X.S., Wang, Z., Helsley, R.N., et al. (2023) Gut Microbiota-derived Trimethylamine N-oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms. Circulation. PMCID: PMC10071415
  30. Park, S.H., Helsley, R.N., Fadhul, T. et al. (2023) Fructose Induced KHK-C Increases ER Stress and Modules Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD. Metabolism. PMID: 37230214
  31. Zelows, M.M., Cady, C., Dharanipragada, N., Mead, A.M., Kipp, Z.A., Bates, E.A., Varadharajan, V., Banerjee, R., Park, S-H, Shelman, N.R., Clarke, H.A., Hawkinson, T.R., Medina, T., Sun, R.C., Lydic, T.A., Hinds, T.D., Brown, J.M., Softic, S., Graf, G.A. and Helsley, R.N. (2023) Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice. Mol Metab. PMCID: PMC10568566
  32. Varadharajan, V., Ramachandiran, L., Massey, W.J., Jain, R., Banerjee, R., Horak, A.J., McMullen, M.R., Huang, E., Bellar, A., Lorkowski, S.W., Guilshan, K., Helsley, R.N., et al. (2024) Membrane Bound O-Acyltransferase (Mboat7) Shapes Lysosomal Lipid Homeostasis and Function to Control Alcohol-Associated Liver Injury. eLife. PMCID: PMC11034944 
  33. Bates, E.A., Kipp, Z.A., Lee, W-H., Martinez, G.J., Weaver, L., Becker, K.N., Pauss, S.N., Creeden, J.F., Anspach, G.A., Helsley, R.N., et al. (2024) FOXS1 is Increased in Liver Fibrosis and Regulates TGFβ Responsiveness and Proliferation Pathways in Human Hepatic Stellate Cells. J Biol Chem. PMCID: PMC10878791 
  34. Hohe, R., Banerjee, R., Cao, S., Jung, B.M., Horak, A.J., Massey, W.J., Varadharajan, W., Zajczenko, N., Burrows, A.C., Dutta, S., Goudarzi, M., Carter, A., Helsley, R.N., et al. (2024) The Nonvesicular Sterol Transporter Aster-C Plays a Minor Role in Whole Body Cholesterol Balance. In Press at Front. Physiol.