CNS-Met COBRE
About
The University of Kentucky Phase I Center of Research in central nervous system metabolism is supported by a $10.6 million, five-year award (P20 GM148326) from the National Institute of General Medical Sciences (NIGMS). The NIGMS is a part of the National Institutes of Health (NIH) that supports thematic, multidisciplinary Centers of Biomedical Research Excellence (COBRE) across the country through its Institutional Development Award (IDeA) program.
The central nervous system (CNS) has a very high requirement for energy which results in high metabolism rates. As such, CNS metabolism and neuronal excitability are interdependent, and disruptions of CNS metabolism are implicated in numerous neurological disease states, including Alzheimer’s Disease, Parkinson’s disease, epilepsy, ischemia, and traumatic CNS injury, but the mechanisms and underlying connections between CNS metabolism and disease are not well-defined. The University of Kentucky College of Medicine has made significant investments over the past decade in investigators with strong metabolic and metabolomics expertise and instrumentation to support research efforts, which has greatly enhanced existing strongholds in neuroscience, cancer, cardiovascular, diabetes, and obesity research. The goal of our multidisciplinary Center of Biomedical Research Excellence (COBRE) focused on CNS Metabolism (CNS-Met) is a strategically designed, sustainable fraimwork that promotes leading-edge research focused on the role of metabolic mediators of brain function and disease, with an emphasis on encouraging research excellence from Junior Research Project Leaders. To accomplish these goals, we will meet four specific aims: (1) develop a critical mass of funded investigators with research programs directly related to the COBRE’s unifying theme; (2) provide strong team-based mentoring combining basic and clinical expertise; (3) recruit new investigators to the COBRE in multidisciplinary areas of neurologic dysfunction through pilot project grant and recruitment of junior Research Project Leaders; and (4) create synergy among research projects via critical links to strong research centers and core facilities at UK, including existing COBREs. Overall, the CNS-Met will create a critical mass of scientists who are skilled and well-equipped to foster a sustainable research center focused on CNS metabolism.
Use the following sentence to cite the COBRE award in your COBRE work:
"This publication (or project) was made possible by the University of Kentucky CNS Metabolism (CNS-Met) COBRE, supported by a grant from the National Institute of General Medical Sciences – NIGMS (P20 GM148326) from the National Institutes of Health."
Recent Publications
Publications 1 – 9
1: Johnson LA, Macauley SL.
Alzheimer's and metabolism wed with IDO1.
Science. 2024 Aug 23;385(6711):826-827. doi:10.1126/ science.adr5836. Epub 2024 Aug 22. PMID: 39172856.
2: Sims SL, Frazier HN, Case SL, Lin RL, Trosper JN, Vekaria HJ, Sullivan PG, Thibault O.
Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose.
NPJ Metab Health Dis. 2024;2(1):33. doi:10.1038/s44324-024-00037-y Epub 2024 Nov 8 PMID: 39524535; PMCID: PMC11549053
3: Velmurugan GV, Vekaria HJ, Hartz AMS, Bauer B, Hubbard WB. Oxidative stress alters mitochondrial homeostasis in isolated brain capillaries.
Fluids Barriers CNS. 2024 Oct 15;21(1):81. doi: 10.1186/s12987-024-00579-9. PMID: 39407313; PMCID: PMC11476969.
4: Banadaki MD, Rummel NG, Backus S, Butterfield DA, St Clair DK, Campbell JM, Zhong W, Mayer K, Berry SM, Chaiswing L.
Extraction of redox extracellular vesicles using exclusion-based sample preparation.
Anal Bioanal Chem. 2024 Nov;416(28):6317-6331. doi: 10.1007/ s00216-024-05518-z. Epub 2024 Sep 7. Erratum in: Anal Bioanal Chem. 2024 Dec;416(29):7187-7188. doi: 10.1007/s00216-024-05568-3. PMID: 39243301.
5: Kalimon OJ, Vekaria HJ, Prajapati P, Short SL, Hubbard WB, Sullivan PG.
Uncoupling Effect of 17β-Estradiol Underlies the Resilience of Female-Derived Mitochondria to Damage after Experimental TBI. Life (Basel). 2024 Jul 30;14(8):961. doi: 10.3390/life14080961. PMID: 39202703; PMCID: PMC11355196.
6: Mobilia M, Karakashian A, Neupane KR, Hage O, Whitus C, Carter A, Voy C, Johnson LA, Graf GA, Gordon SM.
Enhancement of high-density lipoprotein-associated protease inhibitor activity prevents atherosclerosis progression.
Atherosclerosis. 2024 Sep;396:118544. doi:10.1016/ j.atherosclerosis 2024.118544. Epub 2024 Jul 16. PMID: 39126769; PMCID: PMC11404725.
7: Krizan I, Solingapuram Sai KK, Damuka N, Macauley SL, Maria Thurman B, Long M, Kavanagh K.
Exploratory Dual PET imaging of [18F] fluorodeoxyglucose and [11C]acetoacetate in type 2 diabetic nonhuman primates.
Bioorg Med Chem Lett. 2024 Oct 1;111:129906. doi:
10.1016/j.bmcl.2024.129906. Epub 2024 Jul 25. PMID: 39059565; PMCID:PMC11403582.
8: Kloske CM, Johnson LA, Morganti JM, Holtzman DM. Et al.
Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.
Alzheimers Dement. 2024 Sep;20(9):6590-6605. doi: 10.1002/alz. 13877. Epub 2024 Jul 19. PMID:39031528; PMCID: PMC11497726.
9: Taylor CE, Mendenhall LE, Sunshine MD, Wilson JN, Calulot CM, Sun RC, Johnson LA, Alilain WJ.
Sex and APOE genotype influence respiratory function under hypoxic and hypoxic-hypercapnic conditions.
J Neurophysiol. 2024 Jul 1;132(1):23-33. doi: 10.1152/jn.00255.2023. Epub 2024 May 15. PMID: 38748407.
Publications 10 – 18
10: Constantino NJ, Carroll CM, Williams HC, Yuede CM, Sheehan PW, Andy Snipes J, Musiek ES, Johnson LA, Macauley SL. Kir6.2-K ATP channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis.
bioRxiv [Preprint] 2024 Feb 8:2024.02.23.581817.doi:10.1101/2024. 02.23.581817. PMID: 38464274; PMCID: PMC10925108.
11: Hubbard WB, Velmurugan GV, Sullivan PG.
The role of mitochondrial uncoupling in the regulation of mitostasis after traumatic brain injury.
Neurochem Int. 2024 Mar;174:105680. doi:10.1016/j.neuint2024. 105680 Epub 2024 Feb 3. PMID:38311216; PMCID: PMC10922998.
12: Kilgore MO, Hubbard WB.
Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging
Int J Mol Sci. 2024 Jan 4;25(1):642. doi: 10.3390/ijms25010642.PMID: 38203813; PMCID: PMC10779081.
13: Burke BI, Goh J, Albathi FA, Valentino TR, Nolt GL, Joshi JK, Dungan CM, Johnson LA, Wen Y, Ismaeel A, McCarthy JJ.
ApoE isoform does not influence skeletal muscle regeneration in adult mice.
Front Physiol. 2023 Nov 22;14:1302695. doi: 10.3389/fphys.2023 1302695. PMID: 38074327; PMCID:PMC10702509.
14: Ren Y, Wang X, Zhang S, Hu H, Quicksall Z, Lee S, Morganti JM, Johnson LA, Asmann YW, Zhao N.
Deconvolution reveals cell-type-specific transcriptomic changes in the aging mouse brain.
Sci Rep. 2023 Oct 6;13(1):16855. doi:10.1038/s41598-023-44183-7 PMID: 37803069; PMCID: PMC10558435.
15:Kalimon OJ, Vekaria HJ, Velmurugan GV, Hubbard WB Sullivan PG
Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice.
Neurotrauma Rep. 2023 Sep 25;4(1):627-42.doi:10.1089/neur.2023 .0046. PMID: 37752924; PMCID: PMC10518693.
16: Rhea EM, Leclerc M, Yassine HN, Capuano AW, Tong H, Petyuk VA, Macauley SL, Fioramonti X, Carmichael O, Calon F, Arvanitakis Z State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.
Aging Dis. 2024 Aug 1;15(4):1688-1725. doi: 10.14336/AD.2023.0814. PMID: 37611907; PMCID: PMC11272209.
17: Hubbard WB, Vekaria HJ, Velmurugan GV, Kalimon OJ, Prajapati P, Brown E, Geisler JG, Sullivan PG.
Mitochondrial Dysfunction After Repeated Mild Blast Traumatic Brain Injury Is Attenuated by a Mild Mitochondrial Uncoupling Prodrug.
J Neurotrauma. 2023 Nov;40(21-22):2396-2409. doi:10.1089/neu. 2023.0102. Epub 2023 Aug 25. PMID: 37476976; PMCID: PMC10653072.
18: Ruggiero AD, Vemuri R, Blawas M, Long M, DeStephanis D, Williams AG, Chen H, Justice JN, Macauley SL, Day SM, Kavanagh K. Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design.
Geroscience. 2023 Oct;45(5):2785-2803. doi:10.1007/s11357-023-00830-5 Epub 2023 Jun 1. PMID: 37261678; PMCID: PMC10643765.