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Carlos Manlio Diaz Garcia, Ph.D.

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Postdoc awardee presentation and travel award. 13th Intl Conference on Brain Energy Metabolim
2017 - 2020
Ruth L. Kirschstein National Research Service Award (NRSA) individual postdoctoral fellowship (F32)
2016 - 2017
Fix Fund Postdoctoral Fellowship, Department of Neurobiology, Harvard Medical School
Ph.D. awarded with Honorific Mention, National Autonomous University of Mexico
International Travel Award, 57th Annual Meeting of the Biophysical Society
Travel Award, 1st Congress of the Federation of Neuroscience Societies from Latin-America
2010 - 2014
Ph.D. Scholarship, National Council of Science and Technology of Mexico CONACyT
Scholarship, Institute of Science and Technology of Mexico City ICyTDF
Scholarship, Network of Public MacroUniversities of Latin America and the Caribbean
Award for the Best Academic Performance, University of La Habana, Cuba
B.S. in Biochemistry awarded with High Honors, University of La Habana, Cuba

Carlos Manlio Diaz-Garcia is a postdoctoral researcher in the laboratory of Gary Yellen.
Brain metabolism must accommodate a wide dynamic range of energy demands from time to time and from cell type to cell type. Although the metabolic response to increased brain activity is the basis of well-known functional MRI signals, the nature of this metabolic response is still very controversial. It has been demonstrated that metabolism plays a key regulatory role in several neurological conditions, including epilepsy and neurodegenerative diseases. However, little is known about the mechanisms coupling neuronal excitability to metabolism, though the main metabolic pathways have been well established for decades now. The study of real-time dynamics of brain metabolism has been hampered by the insufficient spatial and temporal resolution of the methods, but such limitations can now be overcome by the use of genetically- encoded fluorescent biosensors. I use a combination of genetically-encoded fluorescent biosensors to determine glucose consumption as well as the NADH/NAD+ and ATP/ADP ratios. These sensors can give calibrated quantitative readouts within intact brain tissue, by using two-photon microscopy with either ratiometric or fluorescence lifetime imaging (FLIM). The Ca2+ indicator RCaMP1h and electrophysiologic recordings provide a readout of neuronal activity. Additionally, I measure the NAD(P)H and FAD+ autofluorescence in brain tissue as a proxy for the TCA cycle, and use Clark electrodes to measure the O2 level.
My current goal is to use these methods to study the energy metabolism of neurons and astrocytes in brain slices.
Aim 1 is to characterize the dynamics of glucose and NADH and ATP levels in the astrocytes and neurons (both glutamatergic and GABAergic) in hippocampal slices during resting and active states. This work will also explore the glycolytic contribution to the neuronal activity-induced acceleration of energy metabolism.
Aim 2 is to determine the mechanisms linking the neuronal activity to an increased metabolism, both the triggering stimuli (Na+, K+ and Ca2+ fluxes) and subsequent signaling (such as ionotropic or G-protein coupled receptors and protein kinases).
Aim 3 is to compare the mechanisms coupling neuronal activity to metabolism among neuronal somata, dendrites and axons/synaptic terminals.
This research project should provide definitive answers to these mechanistic questions, a necessary step towards understanding and treating the alterations that occur in disease states.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. F32NS100331 (DIAZ GARCIA, CARLOS MANLIO) Apr 1, 2017 - Mar 31, 2020
    Defining the cellular metabolic responses to brain activity using fluorescent biosensors
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Koveal D, Díaz-García CM, Yellen G. Fluorescent Biosensors for Neuronal Metabolism and the Challenges of Quantitation. Curr Opin Neurobiol. 2020 08; 63:111-121. PMID: 32559637.
  2. Díaz-García CM, Lahmann C, Martínez-François JR, Li B, Koveal D, Nathwani N, Rahman M, Keller JP, Marvin JS, Looger LL, Yellen G. Quantitative in vivo imaging of neuronal glucose concentrations with a genetically encoded fluorescence lifetime sensor. J Neurosci Res. 2019 08; 97(8):946-960. PMID: 31106909.
  3. Díaz-García CM, Yellen G. Neurons rely on glucose rather than astrocytic lactate during stimulation. J Neurosci Res. 2019 08; 97(8):883-889. PMID: 30575090.
    Citations:    Fields:    
  4. García-Delgado N, Velasco M, Sánchez-Soto C, Díaz-García CM, Hiriart M. Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion. Front Endocrinol (Lausanne). 2018; 9:40. PMID: 29556214.
  5. Velasco M, Larqué C, Díaz-García CM, Sanchez-Soto C, Hiriart M. Rat Pancreatic Beta-Cell Culture. Methods Mol Biol. 2018; 1727:261-273. PMID: 29222788.
  6. Carbajal-Ramírez A, García-Macedo R, Díaz-García CM, Sanchez-Soto C, Padrón AM, de la Peña JE, Cruz M, Hiriart M. Neuropathy-specific alterations in a Mexican population of diabetic patients. BMC Neurol. 2017 Aug 25; 17(1):161. PMID: 28841856.
  7. Díaz-García CM, Mongeon R, Lahmann C, Koveal D, Zucker H, Yellen G. Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake. Cell Metab. 2017 Aug 01; 26(2):361-374.e4. PMID: 28768175.
    Citations: 14     Fields:    Translation:AnimalsCells
  8. Velasco M, Díaz-García CM, Larqué C, Hiriart M. Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells. Mol Pharmacol. 2016 Sep; 90(3):341-57. PMID: 27436126.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  9. Diaz-Garcia CM, Agüero-Chapín G, Antunes A, Vasconcelos V. Biological toxins and medicinal chemistry: research and therapeutic tools. Curr Top Med Chem. 2015; 15(7):580. PMID: 25686736.
    Citations:    Fields:    
  10. Hiriart M, Sanchez-Soto C, Diaz-Garcia CM, Castanares DT, Avitia M, Velasco M, Mas-Oliva J, Macias-Silva M, González-Villalpando C, Delgado-Coello B, Sosa-Garrocho M, Vidaltamayo R, Fuentes-Silva D. Hyperinsulinemia is Associated with Increased Soluble Insulin Receptors Release from Hepatocytes. Front Endocrinol (Lausanne). 2014; 5:95. PMID: 24995000.
    Citations: 2     
  11. Diaz-Garcia CM, Morales-Lázaro SL, Sánchez-Soto C, Velasco M, Rosenbaum T, Hiriart M. Role for the TRPV1 channel in insulin secretion from pancreatic beta cells. J Membr Biol. 2014 Jun; 247(6):479-91. PMID: 24676478.
    Citations: 1     Fields:    Translation:AnimalsCells
  12. Marcia Hiriart, Myrian Velasco, Carlos Manlio Diaz-Garcia, Carlos Larqué, Carmen Sánchez-Soto, Alondra Albarado-Ibáñez, Juan Pablo Chávez-Maldonado, Alicia Toledo, Neivys García-Delgado. Islets of Langerhans. Pancreatic Beta Cells in Metabolic Syndrome. 2014; 1-25. View Publication.
  13. Hiriart M, Velasco M, Larqué C, Diaz-Garcia CM. Metabolic syndrome and ionic channels in pancreatic beta cells. Vitam Horm. 2014; 95:87-114. PMID: 24559915.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  14. Domínguez-Pérez D, Diaz-Garcia CM, García-Delgado N, Sierra-Gómez Y, Castañeda O, Antunes A. Insights into the toxicological properties of a low molecular weight fraction from Zoanthus sociatus (Cnidaria). Mar Drugs. 2013 Aug 13; 11(8):2873-81. PMID: 23945599.
    Citations: 2     Fields:    Translation:Animals
  15. Diaz-Garcia CM. The TRPA1 channel and oral hypoglycemic agents: is there complicity in ß-cell exhaustion? Channels (Austin). 2013 Nov-Dec; 7(6):420-2. PMID: 23921548.
    Citations: 1     Fields:    Translation:HumansAnimals
  16. Diaz-Garcia CM, Sanchez-Soto C, Hiriart M. TRPM channels phosphorylation as a potential bridge between old signals and novel regulatory mechanisms of insulin secretion. Curr Diabetes Rev. 2013 Mar 01; 9(2):117-25. PMID: 23092333.
    Citations:    Fields:    Translation:HumansAnimalsCells
  17. Alvarez-Collazo J, Díaz-García CM, López-Medina AI, Vassort G, Alvarez JL. Zinc modulation of basal and ß-adrenergically stimulated L-type Ca2+ current in rat ventricular cardiomyocytes: consequences in cardiac diseases. Pflugers Arch. 2012 Nov; 464(5):459-70. PMID: 23007464.
    Citations: 11     Fields:    Translation:AnimalsCells
  18. Diaz-Garcia CM, Fuentes-Silva D, Sanchez-Soto C, Domínguez-Pérez D, García-Delgado N, Varela C, Mendoza-Hernández G, Rodriguez-Romero A, Castaneda O, Hiriart M. Toxins from Physalia physalis (Cnidaria) raise the intracellular Ca(2+) of beta-cells and promote insulin secretion. Curr Med Chem. 2012; 19(31):5414-23. PMID: 22830340.
    Citations: 3     Fields:    Translation:AnimalsCells
  19. Diaz-Garcia CM, Sanchez-Soto C, Fuentes-Silva D, Leon-Pinzon C, Dominguez-Perez D, Varela C, Rodriguez-Romero A, Castañeda O, Hiriart M. Low molecular weight compounds from Zoanthus sociatus impair insulin secretion via Ca(+2) influx blockade and cause glucose intolerance in vivo. Toxicon. 2012 Feb; 59(2):306-14. PMID: 22155304.
    Citations: 3     Fields:    Translation:AnimalsCells
  20. Diaz-Garcia CM, Sanchez-Soto C, Hiriart M. Toxins that modulate ionic channels as tools for exploring insulin secretion. Cell Mol Neurobiol. 2010 Nov; 30(8):1275-81. PMID: 21046453.
    Citations:    Fields:    Translation:HumansAnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.