- M.S.: Biophysics; Univerzita Pavla Jozefa Šafárika, Slovakia
- Ph.D.: Membrane physiology, Calcium metabolism; Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Slovak Republic
- Postdoctoral: Brain ischemia; Experimental Brain Research Lab, Lund University, Sweden
My research is focused on the fundamental mechanisms of acute brain injury and chronic neurodegenerative disorders. Our studies are centered on processes leading to mitochondrial dysfunction and mechanisms of NAD+ catabolism-related pathophysiology.
We generated transgenic animals expressing mitochondrially-targeted yellow fluorescent protein (eYFP) that allows identification of cell-type specific mitochondria in vivo. These mice are used to examine the effect of acute brain injury on neuronal and non-neuronal mitochondria.
Recently we discovered that NAD+ glycohydrolase CD38 is overexpressed in brain tissue following ischemic insult. CD38 shows increased activity and significantly contributes to cellular NAD+ catabolism.
We are testing the neuroprotective effect of compounds that feed into the NAD+ salvage pathway, as well as inhibit the CD38 activity. Furthermore, we are using molecular techniques study the role of metabolites that are generated downstream of NAD+ catabolism in mechanisms of mitochondrial dysfunction following ischemic insult.
Grants & Contracts:
VA Merit Review Award: "NAD+ catabolism and mitochondrial dysfunction in acute neurodegenerative disease"
Kristián T, Gunilla G, Siesjö BK. The influence of acidosis on hyperglycemic brain damage. Journal of Cerebral Blood Flow and Metabolism 1995 15, 78-87.
Kristián T, OuYang Y-B, Siesjö BK. Calcium-related damage in vivo and in vitro: are different mechanisms involved ? Advances in Neurology 1996 71, 107-118.
Kristián T, Siesjö BK. Calcium-related damage in ischemia. Life Sciences 1996 59, 357-367.
Kristián T, Siesjö BK. Calcium in ischemic cell death. Stroke 1998 29, 705-718.
Kristián T, Gertsch J, Bates T, Siesjö BK. Characteristics of the calcium-triggered mitochondrial permeability transition in non-synaptic brain mitochondria: effect of cyclosporin A and ubiquinone 0. Journal Neurochem 2000 74:1999-2009.
Kristián T, Bernardi P, Siesjo BK (2001) Acidosis promotes the permeability transition in energized mitochondria: Implications for reperfusion injury. J Neurotrauma,18:1059-1074.
Yoshimoto T, Kristián T, Hu B-R, Ouyang Y-B, Siesjo BK (2002) Effect of NXY-059 on secondary mitochondrial dysfunction after transient focal ischemia; comparison with cyclosporin A. Brain Res 932: 99-109.
Kristián T, Weatherby TM, Bates TE, Fiskum G (2002) Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria. J of Neurochem.83: 1207-1308.
Kristián T (2004) Metabolic stages, mitochondria, and calcium in hypoxic/ischemic brain damage. Cell Calcium 36 : 221-233.
Kristián T, Fiskum G (2004) A Fluorescence-Based Technique for Screening Compounds that Protect Against Damage to Brain Mitochondria. Brain Res Protocols 13:176-182.
Schuh RA, Kristián T, Fiskum G (2005) Calcium-dependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein (CREB). J Neurochem 92(2): 388-394.
Kristián T, Hopkins IB, McKenna MC, Fiskum G (2006). Isolation of mitochondria with high respiratory control from primary cultures of neurons and astrocytes using nitrogen cavitation. J Neurosci Methods 152:136-143.
Chandrasekaran K, Hazelton JL, Wang Y, Fiskum G, Kristián T (2006) Neuron-specific conditional expression of a mitochondrially-targeted fluorescent protein in mice. J Neuroscience, 26:13123-13127.
Kristián T, Pivovarova NB, Fiskum G, Andrews SB (2007): Calcium-induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention. J Neurochem. 102(4):1346-56.
Hazelton JL, Petrasheuskaya M, Fiskum G, Kristián T. Cyclophilin D is expressed predominantly in mitochondria of GABA-ergic interneurons. J Neurosci Res. 2009 87(5):1250-1259.
Balan I, Fiskum G, Kristián T. Visualization and quantification of NAD(H) in brain sections by a novel histo-enzymatic nitrotetrazolium blue staining technique. Brain Res. 2010 1316:112-9.
Kristián T. Isolation of mitochondria from CNS. Current Protocols in Neurosci. 2010 Chapter 7: Unit 7.22.
Kristián T, Balan I, Schuh R, Onken M. Mitochondrial dysfunction and NAD+ catabolism as mechanisms of cell death and promising targets for neuroprotection. J Neurosci Res 2011 89:1946-55.
Kristián T, Hu BR. Guidelines for using mouse global cerebral ischemia models. Transl. Stroke Res. 2013 4:343-350.
Owens K, Park JH, Schuh R, Kristián T. Mitochondrial dysfunction and NAD+ metabolism alterations in the pathophysiology of acute brain injury. Transl. Stroke Res. 2013
Faculty members: Update your contact information and create a profile.