Research Program

The focus of my research laboratory is mitochondrial uncoupler drug development for the treatment of ageing, obesity and related metabolic diseases.

Selected publications (of 99)

1. 2024 - Zhou M, Li C, Byrne FL, Vancuylenburg CS, Olzomer EM, Hargreaves A, Wu LE, Shackel NA, Santos WL, Hoehn KL. Beneficial effects of MGL-3196 and BAM15 combination in a mouse model of fatty liver disease. Acta Physiologica. 2024 Aug 16:e14217. doi: 10.1111/apha.14217.
2. 2024 – Beretta M, Dai Y, Olzomer EM, Vancuylenburg CS, Santiago-Rivera JA, Philp AM, Hargett SR, Li K, Shah DP, Chen SY, Alexopoulos SJ, Li C, Harris TE, Lee B, Wathier M, Cermak JM, Tucker SP, Turner N, Bayliss DA, Philp A, Byrne FL, Santos WL and Hoehn KL. Liver-selective imidazolopyrazine mitochondrial uncoupler SHD865 reverses adiposity and glucose intolerance in mice. Diabetes. March 1;73(3):374-384. doi: 10.2337/db23-0233. 
3. 2024 - Chen SY, Telfser AJ, Olzomer EM, Vancuylenberg CS, Zhou M, Beretta M, Li C, Alexopoulos SJ, Turner N, Byrne FL, Santos WL, Hoehn KL. Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice. Clinical Science. Feb 21;138(4):173-187. doi: 10.1042/CS20231016.
4. 2023 – Chen SY, Beretta M, Olzomer EM, Shah DP, Wong DYH, Alexopoulos SJ, Aleksovska I, Salamoun JM, Garcia CJ, Cochran BJ, Rye KA, Smith GC, Byrne FL, Morris MJ, Santos WL, Cantley J, Hoehn KL. Targeting negative energy balance with calorie restriction and mitochondrial uncoupling in db/db mice. Molecular Metabolism. Mar;69:101684. doi: 10.1016/j.molmet.2023.101684.
5. 2023 – Chen SY, Beretta M, Olzomer EM, Alexopoulos SJ, Shah DP, Byrne FL, Salamoun JM, Garcia CJ, Smith GC, Larance M, Philp A, Turner N, Santos WL, Cantley J, and Hoehn KL. Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice. BBA - Molecular Basis of Disease. doi: 10.1016/j.bbadis.2023.166908
6. 2023 - Murray JH, Burgio AL, Beretta M, Hargett SR, Harris TE, Olzomer E, Grams RJ, Garcia CJ, Li C, Salamoun JM, Hoehn KL*, Santos WL*. Oxadiazolopyridine Derivatives as Efficacious Mitochondrial Uncouplers in the Prevention of Diet-Induced Obesity. Journal of Medicinal Chemistry. Mar 23;66(6):3876-3895. doi: 10.1021/acs.jmedchem.2c01573.
7. 2022 - Yeudall S, Upchurch CM, Seegren PV, Pavelec CM, Greulich J, Lemke MC, Harris TE, Desai BN, Hoehn KL, Leitinger N. Macrophage acetyl-CoA carboxylase regulates acute inflammation through control of glucose and lipid metabolism. Science Advances. Nov 25;8(47):eabq1984. doi: 10.1126/sciadv.abq1984. Epub 2022 Nov 23.
8. 2021 - Chen SY, Beretta M, Alexopoulos SJ, Shah DP, Olzomer EM, Hargett SR, Childress ES, Salamoun JM, Aleksovska I, Roseblade A, Cranfield C, Rawling T, Quinlan KGR, Morris MJ, Tucker SP, Santos WL and Hoehn KL. Mitochondrial uncoupler SHC517 reverses obesity in mice without affecting food intake. Metabolism. Apr;117:154724. doi: 10.1016/j.metabol.2021.154724.
9. 2020 – Alexopoulos, A.J.; Chen, S-Y.; Brandon, A.E.; Salamoun, J.; Garcia, C.J.; Beretta, M.; Olzomer, E.; Byrne, F.B.; Shah, D.; Lawrence, R.; Carrive, P.; Tucker, S.P.; Cooney, G.J.; Santos, WL; Hoehn KL. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice. Nature Communications. May 14;11(1):2397. doi: 10.1038/s41467-020-16298-2.
10. 2020 – Salamoun J, Garcia C, Hargett S, Murray J, Chen SY, Beretta M, Alexopoulos S, Shah D, Olzomer E, Tucker S, Hoehn KL*, and Santos WL*. 6-Amino-[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol Derivatives as Efficacious Mitochondrial Uncouplers in STAM Mouse Model of Non-alcoholic Steatohepatitis. Journal of Medicinal Chemistry. Jun 11;63(11):6203-6224. doi: 10.1021/acs.jmedchem.0c00542. *co-corresponding
11. 2020 – Childress E, Salamoun J, Hargett SH, Alexopoulos SJ, Chen SY, Shah D, Santiago-Rivera J, Garcia C, Dai Y, Tucker SJ, Hoehn KL*, and Santos WL*. [1,2,5]Oxadiazolo[3,4-b]pyrazine-5,6-diamine Derivatives  as Mitochondrial Uncouplers for the Potential Treatment of Nonalcoholic Steatohepatitis. Journal of Medicinal Chemistry. Feb 4. doi: 10.1021/acs.jmedchem.9b01440 *co-corresponding
12. 2020 - Byrne FL, Olzomer EM, Marriott GR, Quek LE, Katen A, Su J, Nelson ME, Hart-Smith G, Larance M, Sebesfi VF, Cuff J, Martyn GE, Childress E, Alexopoulos SJ, Poon IK, Faux MC, Burgess AW, Reid G, McCarroll JA, Santos WL, Quinlan KG, Turner N, Fazakerley DJ, Kumar N, and Hoehn KL. Phenotypic screen for oxygen consumption rate identifies an anti-cancer naphthoquinone that induces mitochondrial oxidative stress. Redox Biology. Jan;28:101374. doi: 10.1016/j.redox.2019.101374.
13. 2020 - Knights AJ, Vohralik EJ, Houweling PJ, Stout ES, Norton LJ, Alexopoulos SJ, Yik JJ, Mat Jusoh H, Olzomer EM, Bell-Anderson KS, North KN, Hoehn KL, Crossley M, Quinlan KGR. Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3). Nature Communications. Jun 10;11(1):2922. doi: 10.1038/s41467-020-16758-9
14. 2018 – Byrne FL, Hargett SR, Lahiri S, Roy RJ, Berr SS, Caldwell SH, Hoehn KL. Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver Tumor Growth. Cancers. Sep 5;10(9). doi: 10.3390/cancers10090312.
15. 2017 – Nelson ME, Lahiri S, Chow JDY, Byrne FL, Hargett SR, Breen DS, Olzomer EM, Wu LE, Cooney GJ, Turner N, James DE, Slack-Davis JK, Lackner C, Caldwell SH, and Hoehn KL. Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defense and promoting cell survival. Nature Communications. Mar 14;8:14689. doi: 10.1038/ncomms14689.
16. 2015 – Healy ME, Chow JDY, Byrne FL, Breen DS, Leitinger N, Li C, Lackner C, Caldwell SH, and Hoehn KL. Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine. Journal of Hepatology. Mar;62(3):599-606.
17. 2015 – Serasinghe MN, Weider SY, Thibaud TR, Elkholi R, Asciolla JJ, Yao JL, Jabado O, Hoehn K, Kageyama Y, Sesake H, and Chipuk JE. Mitochondrial division is requisite to RAS-induced transformation and targeted by mitooncogenic MAPK pathway inhibitors. Molecular Cell. Feb 5;57(3):521-536.
18. 2015 – Kashatus JA, Nascimento A, Myers L, Sher A, Byrne FL, Hoehn KL, Counter CM, and Kashatus DF. Erk2 phosphorylation of Drp1 promotes mitochondrial fission and Ras-driven tumor growth. Molecular Cell. Feb 5;57(3):537-551.
19. 2013 – Taddeo EP, Laker RC, Breen DS, Akhtar YN, Kenwood BM, Liao JA, Zhang M, Fazakerley DJ, Tomsig JL, Chow JD, Lynch KR, Chokki M, Molkentin JD, Turner N, James DE, Yan Z, and Hoehn KL. Opening of the Mitochondrial Permeability Transition Pore is Required for Insulin Resistance in Skeletal Muscle. Molecular Metabolism. Nov 26;3(2):124-34.
20. 2013 – Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomsig JL, Okabe K, Columbus L, Lynch KR, Ravichandran KS, Yan Z, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, and Hoehn KL. Identification of a Novel Mitochondrial Uncoupler that Does Not Depolarize the Plasma Membrane. Molecular Metabolism. Nov 28;3(2):114-23.
21. 2011 – Park D, Han C, Elliott MR, Kinchen JM, Trampont PC, Das S, Collins S, Lysiak JJ, Hoehn KL, and Ravichandaran KS. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. Aug 21; 477(7363):220-4.
22. 2010 - Hoehn KL*, Turner N*, Swarbrick MM, Wilks D, Preston E, Phua Yuwei, Joshi H, Furler SM, Larance M, Hegarty BD, Leslie SJ, Pickford R, Hoy AJ, Kraegen EW, James DE, and Cooney GJ. Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole body energy expenditure or adiposity. Cell Metabolism. Jan; 11(1):70-6.  
23. 2009 - Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, James DE. Insulin resistance is a cellular antioxidant defense mechanism. PNAS. Oct 20; 106 (42):17787-92.
24. 2008 - Hoehn KL, Hohnen-Behrens C, Cederberg A, Turner N, Wu L, Yuasa T, Ebina Y, James DE.  IRS-1 Independent Defects Define Major Nodes of Insulin Resistance. Cell Metabolism. May; 7(5):421-33.

Education

• Bachelor degree in Chemistry, Univ. of Northern Colorado 2000
• Bachelor degree in Biology, Univ. of Northern Colorado 2000
• Master of Science degree in Biochemistry, Colorado State University 2001
• PhD degree in Biochemistry and Molecular Biology, Colorado State University 2005

Research Projects

• To understand the role of acetyl-CoA carboxylase enzymes in nutrient metabolism
• To develop new molecules that improve healthy ageing
• To develop molecules that reverse obesity and related metabolic disorders
• To determine how dietary nutrients contribute to cancer initiation and/or progression