Kyle Hoehn

Research Program

My research team investigates mitochondrial function and metabolism in both normal physiology and disease states. We have discovered a novel class of small molecule mitochondrial uncouplers that boost metabolism and decrease oxidative stress. The current focus of our research involves the therapeutic potential of mitochondrial uncouplers to slow aging-related metabolic decline and to reverse metabolic disorders related to obesity, diabetes, and fatty liver disease. 

Selected publications (of 76)

1. 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.
2. 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.
3. 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.
4. 2020 - Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Molecular Medicine. Jun 10:e12088. doi: 10.15252/emmm.202012088. 
5. 2020 - Murray J, Hargett S, Hoehn KL*, and Santos W*L. Anilinopyrazines as potential mitochondrial uncouplers, Bioorganic Medicinal Chemistry Letters. Apr 15;30(8):127057. doi: 10.1016/j.bmcl.2020.127057.*co-corresponding.
6. 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. 
7. 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.
8. 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.
9. 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, LacknerC, 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.
10. 2015 – Healy ME, Chow JDY, Byrne FL, Breen DS, Leitinger N, Li C, LacknerC, 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.  
17. 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.
18. 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 identify new molecules that improve healthy ageing
• To develop molecules that reverse obesity and metabolic diseases
• To develop new and better chemical tools for assessing mitochondrial function
• To determine how dietary nutrients contribute to cancer initiation and/or progression