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Robert N. Helsley, PhD

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859-257-3446
robert.helsley@uky.edu
BBSRB Rm: B347, 741 South Limestone Street

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. Highlighted in Rockefeller University Press Releases on 05/06/2014. Highlighted in Science Daily, The Medical News, MedicalXpress, Newswise, Scicasts, and Diagnostic and Interventional Cardiology.
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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. PMC6850774
  16. 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
  17. 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
  18. Helsley, R.N. and Softic, S. (2020) Fructose metabolism by the guts cuts liver fat. J Mol Med. 98(5):733-734. PMID: 32318746
  19. 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. PMC7311702 
  20. 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. PMC7469577
  21. 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
  22. 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). PMC8528699
  23. 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. PMC8361265
  24. 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. PMC8813054
  25. 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. PMC8853661.
  26. 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
  27. 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

  28. 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

  29. 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

  30. 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. PMC10071415
  31. 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
  32. 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. PMC10568566
  33. 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. PMC11034944 
  34. 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. PMC10878791 
  35. 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. Front. Physiol. PMC11061533 
  36. Helsley, R.N. #, Zelows, M.M., Noffsinger, V.P., Anspach, G.B., Dharanipragada, N., Mead, A.E., Cobo, I., Carter, A., Wu, Q., Shalaurova, I., Saito, K., Morganti, J.M., Gordon, S.M., and Graf, G.A.# (2025) Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers Apolipoprotein B Containing Lipoproteins in Mice. ATVB. PMC12286734. # co-corresponding authors. 
  37. Selected as Editors Pick and Cover for August Issue (2025).
  38. Anspach, G.B., Kaur, R., Chauhan, I., Savage, E.L., Poole, B., Noffsinger, V.P., Fu, X., Wang, Z., Temel, R.E., Gordon, S.R., Helsley, R.N., and Graf, G.A. (2025) ABCG5 ABCG8-independent Mechanisms Fail to Maintain Sterol Balance in Mice Fed a High Cholesterol Diet. JLR. PMC12550799
  39. Orabi, D., Massey, W.J., Fung, K.K, Varadharajan, V., Ramachandiran, I., Banerjee, R., Silver, D.J., Osborn, L.J., Brown, A.L., Marshall, S., Ferguson, D., Cao, S., Schugar, R.C., Finney, C., Neumann, C., Burrows, A.C., Horak, A.J., Pathak, P., Helsley, R.N., Bulfon, D., Zimmermann, R., Leung, Y.H., Madiraju, S.R.M., Prentki, M., Lee, R.G., Mullick, A.E., Zergeeva, O., Dasarathy, S., Lee, Z., Allende, D.S., Aucejo, F., Lathia, J.D., and Brown, J.M. (2025) The Lipid Hydrolase ABHD6 is a Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Related Hepatocellular Carcinoma. BioRxiv. In peer review at Mol Metab. PMC12324370
  40. Turner, M.B., Pangilinan, H-R, Park, S-H, Angoma, B., Helsley, R.N., and Loria, A.S. (2025) Adipocyte-specific Deletion of the Mineralocorticoid Receptor Improves Glucose Homeostasis and Associates With FGF21-adiponectin Signaling in Obese Male Mice. Diabetes Obes Metab. PMID: 41153082.
  41. Anspach, G.B., Flight, R.M., Park, S-H., Moseley, H.N.B., and Helsley, R.N. (2026) An Integrated Multi-omic Analysis Reveals Novel Gene-Metabolite Relationships in Human Steatohepatitic Hepatocellular Carcinoma. MedRxiv doi: https://doi.org/10.64898/2026.01.28.26344977. In peer review at JLR.
  42. Sewell, K.M., Oriakh, K., Tenlep, S.Y.N., Weaver, M., Bawa, M.S., Vsevolozhskaya, O., Park, S-H., Helsley, R.N., Softic, S., and Rashid, C.S. (2026) A Ubiquitious Organophosphate Flame Retardant Disrupts Energy and Glucose Homeostasis in Mice. Ecotoxicol Environ Saf. PMID: 41650571
  43. Ganjayi, M.S., Krauss, T.A., Demster, G.E., Park, S-H., Anspach, G.B., Anthony, S.R., Wang, S., Tranter, M., Helsley, R.N., and Baumann, C.W. (2026) Systemic Consequences of Chronic Ethanol Intake: From Microbiome Shifts to Metabolic Impairment. In-press at Compr Physiol.