Krzystztof Hyrc, PhD

Assistant Professor of Neurology

Phone314-362-4876

Emailhyrck@wustl.edu

Research Interests

Dr. Hyrc is primarily interested in ionic mechanisms of excitotoxic neuronal cell death. He specializes in intracellular ion concentration measurements using optical techniques, particularly low affinity calcium indicators.

Intracellular calcium regulation; excitotoxicity; fluorescent ion indicators; live cell imaging; image analysis;

 

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Education

  • Undergraduate (Biology), M.S: Jagiellonian University, Krakow Poland (1981)
  • Graduate (Biophysics), PhD: Jagiellonian University, Krakow Poland (1987)
  • Postdoctoral training (Biophysics): University of Miami, Miami, FL (1990)
  • Postdoctoral training (Neuroscience): Washington University, St. Louis, MO (2000)

Publications

  • Hyrc KL, Froncisz W., Panz T, Erythrocyte surface charge -a spin label study. Studia Biophysica 1984; 103:119-125.Hyrc KL, Cieszka K, Panz, Calculation of the total cell surface charge density based on electrophoretic mobility-ionic strength relationships. Studia Biophysica 1988; 128: 127-135.Hyrc KL, Cieszka K, Cell surface charge of pigmented and non-pigmented melanoma cells. Studia Biophysica 1988; 128; 113-125.Hyrc KL, Rose B, The action of v-src on gap junctional permeability is modulated by pH. Journal of Cell Biology 1990; 110; 1217-1226.Burczyk J, Hyrc KL, Separation effects of pH on Chlorella cells of different strains in two phase system. Journal.of Plant Physiology 1992; 140; 66-69.

    Hyrc KL, Wilczek A, Cieszka K, “Electrophoretic heterogeneity of pigmented hamster melanoma cells. Pigment Cell Research 1993; 6; 100-110.

    Hyrc KL, Handran SD, Rothman SM, Goldberg MP, Ionized intracellular calcium concentration predicts excitotoxic neuronal death; observations with low-affinity fluorescent calcium indicators. Journal of Neuroscience 1997; 17; 6669-6677.

    McDonald JW, Althomsons SP, Hyrc KL, Choi DW., Goldberg MP, Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nature Medicine 1998; 4; 291-297.

    Hasbani MJ, Hyrc KL, Faddis B., Romano, Goldberg MP, Distinct roles for sodium, chloride and calcium in excitotoxic dendritic injury. Experimental. Neurology 1998; 154; 241-258.

    Hyrc KL, Bownik JM, Goldberg MP, Properties of BTC/AM, a low affinity calcium indicator in cultured neurons. Cell Calcium 1998; 24; 156-175.

    Hyrc K., Bownik JM, Goldberg MP, Ionic selectivity of low affinity ratiometric calcium indicators: mag-fura-2, fura-2FF and BTC. Cell Calcium 2000; 27; 75-86.

    Romano C, Miller JK, Hyrc KL, Dikranian S, Mennerick S, Takeuchi Y, Goldberg MP, O’Malley KL, Covalent and noncovalent interactions mediate metabotropic glutamate receptor mGlu(5) dimerization. Molecular Pharmacology 2001; 59 : 46-53.

    De Erausquin GA, Hyrc KL, Dorsey DA, Mamah D, Dokucu M, Masca D, Walton T, Dikranian K, Soriano M, Garcia Verdugo JM, Goldberg MP, Dugan LL, Nuclear translocation of nuclear transcription factor-kappa B by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons. Molecular Pharmacology 2003; 63; 784-90.

    Wang XO, Xiao AY, Sheline C, Hyrc KL, Yang A, Goldberg MP, Choi DW, Ping Yu S, Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. Journal of Cell Science 2003; 116(Pt 10); 2099-110.

    Dorsey DA, Masco DH, Dikranian K, Hyrc K, Masciotra L, Faddis B, Soriano M, Gru AA, Goldberg MP, de Erausquin GA. Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons. Apoptosis. 2006; 11(4):535-44.

    Liu JJ, Shin JH, Hyrc KL, Liu S, Lei D, Holley MC, Bao J. Stem cell therapy for hearing loss: Math1 overexpression in VOT-E36 cells. Otol Neurotol. 2006; 27(3): 414-21.

    Rothman SM, Perry G, Yang XF, Hyrc KL, Schmidt BF. Optical Suppression of Seizure-Like Activity with an LED. Epilepsy Res. 2007 74(2-3):201-9.

    Hyrc KL, Rzeszotnik Z, Kennedy BR, Goldberg MP, Determining calcium concentration in heterogeneous model systems using multiple indicators. Cell Calcium 2007; 42(6):576-89.

    Wu S, Hyrc KL, Moulder KL, Lin Y, Warmke T, Snider BJ, Cellular  calcium deficiency plays a role in neuronal death caused by proteasome inhibitors.  J. Neurochem. 2009;109;125-136.

    Zhang HX, Hyrc KL, Thio LL, The glycine transport inhibitor sarcosine is an  NMDA receptor co-agonist that differs from glycine J Physiol. 2009; 587(13):3207-20.

    Kim E, Hyrc KL, Speck J, Lundberg YW, Salles FT, Kachar B, Goldberg MP, Warchol ME, Ornitz DM. Regulation of cellular calcium in vestibular supporting cells by Otopetrin 1. J Neurophysiol. 2010;104(6):3439-50.

    Crawford DC, Chang CY, Hyrc KL, Mennerick S., Calcium-independent inhibitory G-protein signaling induces a persistent form of hippocampal synaptic plasticity, J Neurosci. 201; 31(3):979-91.

    Kim E, Hyrc KL, Speck J, Salles FT, Lundberg YW, Goldberg MP, Kachar B, Warchol ME, Ornitz DM, Missense mutations in Otopetrin 1 affect subcellular localization and inhibition of purinergic signaling in vestibular supporting cells Mol Cell Neurosci. 2011; 46(3):655-61.

    Zeng C, Vangveravong C, Jones LA, Hyrc KL, Chang KC, Xu j, Rothfuss JM, Goldberg MP, Hotchkiss RS, Mach RH, Characterization and evaluation of two novel fluorescent sigma-2 receptor ligands as proliferation probes,  Molecular Imaging, 2011; 10(6):420-33.

    D’Avanzo N, Hyrc K, Enkvetchakul D, Covey DF, Nichols CG. Enantioselective protein-sterol interactions mediate regulation of both prokaryotic and eukaryotic inward rectifier K+ channels by cholesterol. PLoS One. 2011; 6(4):e19393.

    Toib A, Zhang HX, Broekelmann TJ, Hyrc KL, Guo Q, Chen F, Remedi MS, Nichols CG. Cardiac specific ATP-sensitive K(+) channel (K(ATP)) overexpression results in embryonic lethality. J Mol Cell Cardiol. 2012; 53(3):437-45.

    Zhang S, Hyrc K, Wang S, Wice BM. Xenin-25 increases cytosolic free calcium levels and acetylcholine release from a subset of myenteric neurons.Am J Physiol Gastrointest Liver Physiol. 2012; 303(12):G1347-55.

    Lin Z, Perez P, Sun Z, Liu JJ, Shin JH, Hyrc KL, Samways D, Egan T, Holley MC, Bao J. Reprogramming of single-cell-derived mesenchymal stem cells into hair cell-like cells.Otol Neurotol. 2012; 33(9):1648-55.

    Wang S, Makhina EN, Masia R, Hyrc KL, Formanack ML, Nichols CG. Domain organization of the ATP-sensitive potassium channel complex examined by fluorescence resonance energy transfer. J Biol Chem. 2013; 288(6):4378-88.

    Zhu T, Chappel JC, Hsu FF, Turk J, Aurora R, Hyrc K, De Camilli P, Broekelmann TJ, Mecham RP, Teitelbaum SL, Zou W. Type I phosphotidylinosotol 4-phosphate 5-kinase γ regulates osteoclasts in a bifunctional manner. J Biol Chem. 2013; 288(8):5268-77.

    Shen H, Hyrc KL, Goldberg MP, Maintaining Energy Homeostasis Is an Essential Component of Wlds Mediated Axon Protection. Neurobiol Dis. 2013; 59C:69-79.

    Hyrc KL, Minta A., Escamilla, PR, Chan PPL, Meshik XA, Goldberg MP. Properties of Asante Calcium Red – a novel family of long excitation wavelength indicators. Cell Calcium 2013;54(4) 20-33.

    Zhang S., Wang S., Puhl MD., Jiang X,; Hyrc KL., Laciny E., Wallendorf MJ., Pappan KL., Coyle JT., Wice BM., Global biochemical profiling identifies beta-hydroxypyruvate as a potential mediator of type 2 diabetes in mice and humans. Diabetes 2015; 64(4) 1383-1393.

    Schindler SE, McCall JG, Yan P, Hyrc KL, Li M, Tucker CL, Lee JM, Bruchas MR, Diamond MI.Photo-activatable Cre recombinase regulates gene expression in vivo. Sci Rep. 2015; 5:13627 1-8.

    Wakle-Prabagaran M, Lorca RA, Ma X, Stamnes SJ, Amazu C, Hsiao JJ, Karch CM, Hyrc KL, Wright ME, England SK. BKCa channel regulates calcium oscillations induced by alpha-2-macroglobulin and LRP1 in human myometrial cells. Proc. Natl. Aced. Sci. 2016; 113(16):E2335-44.

    Mayer AL, Higgins CB, Heitmeier MR, Kraft TE, Qian X, Crowley JR, Hyrc KL, Beatty WL, Yarasheski KE, Hruz PW, DeBosch BJ.  SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. Sci Rep. 2016; 6:38586.